Disease Markers https://www.hindawi.com The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Increased Levels of S100A8/A9 in Patients with Peritonsillar Abscess: A New Promising Diagnostic Marker to Differentiate between Peritonsillar Abscess and Peritonsillitis Tue, 17 Oct 2017 07:11:58 +0000 http://www.hindawi.com/journals/dm/2017/9126560/ Peritonsillar abscess (PTA) is a very frequent reason for urgent outpatient consultation and otolaryngological hospital admission. Early, correct diagnosis and therapy of peritonsillar abscess are important to prevent possible life-threatening complications. Based on physical examinations, a reliable differentiation between peritonsillar cellulitis and peritonsillar abscess is restricted. A heterodimeric complex called calprotectin consists of the S100 proteins A8 and A9 (S100A8/A9) and is predominantly expressed not only in monocytes and neutrophils but also in epithelial cells. Due to its release by activated phagocytes at local sites of inflammation, we assumed S100A8/A9 to be a potential biomarker for peritonsillar abscess. We examined serum and saliva of patients with peritonsillitis, acute tonsillitis, peritonsillar abscess, and healthy controls and found significantly increased levels of S100A8/A9 in patients with PTA. Furthermore, we could identify halitosis, trismus, uvula edema, and unilateral swelling of the arched palate to be characteristic symptoms for PTA. Using a combination of these characteristic symptoms and S100A8/A9 levels, we developed a PTA score as an objective and appropriate tool to differentiate between peritonsillitis and peritonsillar abscess with a sensitivity of 92% and specificity of 93%. Christoph Spiekermann, Antonella Russo, Markus Stenner, Claudia Rudack, Johannes Roth, and Thomas Vogl Copyright © 2017 Christoph Spiekermann et al. All rights reserved. Association between Recipient IL-15 Genetic Variant and the Prognosis of HBV-Related Hepatocellular Carcinoma after Liver Transplantation Sun, 15 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/1754696/ Objective. To investigate the association of donor and recipient IL-15 genetic variants with HCC recurrence and prognosis after LT. Methods. A total of 112 liver transplant patients with HBV-related HCC were enrolled. IL-15 rs10519613 and rs13122930 were genotyped in donors and recipients. Results. Recipient IL-15 rs10519613 polymorphism was found to be significantly related to HCC recurrence after LT. In multivariate analysis, tumor thrombus, UCSF criteria, and recipient IL-15 rs10519613 genotypes were independent predictive factors of HCC recurrence after LT. Kaplan-Meier survival analysis demonstrated that patients with recipient IL-15 rs10519613 CA/AA genotypes had a decreased disease-free survival and overall survival than those with the CC genotype. Recipient IL-15 rs10519613 genetic variant could improve survival prediction when combined with the UCSF criteria. Furthermore, Cox proportional hazard regression analysis revealed that tumor size (, ), tumor thrombus (, ), UCSF criteria (, ), and recipient IL-15 rs10519613 genotype (, ) were independent factors of predicting DFS and OS. Conclusions. Recipient IL-15 rs10519613 polymorphism was associated with HCC recurrence after LT and might be a potential genetic marker for the clinical outcome of HCC patients treated with LT. Tao Zhang, Yuan Liu, Xu Peng, Junwei Fan, and Zhihai Peng Copyright © 2017 Tao Zhang et al. All rights reserved. Detection of Pathological Changes in the Aorta during Thoracic Aortic Aneurysm Progression on Molecular Level Thu, 12 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/9185934/ The progression of thoracic aortic aneurysm depends on regulation of aortic wall homeostasis and on changes in the structural components of the extracellular matrix, which are affected by multiple molecular signalling pathways. We decided to correlate the diameter of ascending thoracic aneurysm with gene expression of inflammation markers (IL-6, CRP), cytokine receptors (IL-6R, TNFR1, and TNFR2), and extracellular matrix components (Emilin-1, MMP9, and TIMP) for detection of the degree of pathological process of TAA formation. The experimental group was divided into three groups according to the diameter of the aortic aneurysm. Whole blood and tissue samples were properly collected and used for nucleic acid, chromatin, and protein isolation. The mRNA levels were detected by qRT-PCR. For the detection of protein levels a Cytokine Array IV assay kit was used in combination with a biochip analyzer. In aortic tissue, significant positive correlations were found between increased mRNA levels of inflammatory cytokines (CRP and IL-6) on both mRNA levels in tissue and protein from the blood with maximum in stage 3. Changes of gene expression of selected genes can be used for the experimental study of the inflammatory receptor inhibitors during trials targeted on slowing down the progress of aortic wall aneurysm. Miroslava Rabajdová, Peter Urban, Ivana Špaková, Artemiou Panagiotis, Michaela Ferenčáková, Dušan Rybár, Nikita Bobrov, František Sabol, and Mária Mareková Copyright © 2017 Miroslava Rabajdová et al. All rights reserved. Association of ABO Blood Types and Clinicopathological Features of Prostate Cancer Mon, 09 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/9237481/ Purpose. To investigate the association between ABO blood types and clinicopathological characteristics in patients with prostate cancer (PC). Methods. A total of 237 pathologically diagnosed PC patients were enrolled. All patients were classified as low–middle or high-risk group. The correlation of ABO blood types with high-risk PC was determined by univariate and multivariate regression analysis. Results. Data indicated 144 (85.7%) patients were stratified as high risk in the non-O group, while 50 (72.5%) patients in the O group (). However, there was no significant difference regarding PSA, Gleason score, stage, or metastasis between O and non-O group (). Univariate logistic regression analyses revealed PSA, Gleason score, and blood type non-O were all correlated with high-risk PC (OR = 1.139, ; OR = 9.465, ; OR = 2.280, , resp.). In the stepwise multivariate regression analysis, the association between blood type non-O and high-risk PC remained significant (OR = 33.066, 95% CI 2.391–457.323, and ) after adjusting for confounding factors as well as PSA and Gleason score. Conclusion. The present study firstly demonstrated that non-O blood type was at higher risk of aggressive PC compared with O type, suggesting that PC patients with non-O blood type should receive more attention in clinical practice. Fang-Ming Wang, Yan Zhang, Gui-Ming Zhang, Ya-Nan Liu, Li-Jiang Sun, and Yong Liu Copyright © 2017 Fang-Ming Wang et al. All rights reserved. Predictive Role of F2-Isoprostanes as Biomarkers for Brain Damage after Neonatal Surgery Sun, 08 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/2728103/ Objective. Neonates have a high risk of oxidative stress during anesthetic procedures. The predictive role of oxidative stress biomarkers on the occurrence of brain injury in the perioperative period has not been reported before. Methods. A prospective cohort study of patients requiring major surgery in the neonatal period was conducted. Biomarker levels of nonprotein-bound iron (NPBI) in plasma and F2-isoprostane in plasma and urine before and after surgical intervention were determined. Brain injury was assessed using postoperative MRI. Results. In total, 61 neonates were included, median gestational age at 39 weeks (range 31–42) and weight at 3000 grams (1400–4400). Mild to moderate brain lesions were found in 66%. Logistic regression analysis showed a significant difference between plasma NPBI in patients with nonparenchymal injury versus no brain injury: 1.34 umol/L was identified as correlation threshold for nonparenchymal injury (sensitivity 67%, specificity 91%). In the multivariable analysis, correcting for GA, no other significant relation was found with the oxidative stress biomarkers and risk factors. Conclusion. Oxidative stress seems to occur during anaesthesia in this cohort of neonates. Plasma nonprotein-bound iron showed to be associated with nonparenchymal injury after surgery, with values of 1.34 umol/L or higher. Risk factors should be elucidated in a more homogeneous patient group. L. J. Stolwijk, P. M. A. Lemmers, M. Y. A. van Herwaarden, D. C. van der Zee, F. van Bel, F. Groenendaal, M. L. Tataranno, M. Calderisi, M. Longini, F. Bazzini, M. J. N. L. Benders, and G. Buonocore Copyright © 2017 L. J. Stolwijk et al. All rights reserved. Soluble Urokinase Plasminogen Activator Receptor and the Risk of Coronary Artery Disease in Young Chinese Patients Wed, 04 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/4719403/ Background. Soluble urokinase plasminogen activator receptor (suPAR) is a novel marker of chronic inflammation and is considered to be a risk factor for coronary artery disease (CAD) in Caucasians. This study investigated the role of suPAR in young Chinese patients with CAD. Methods. The study involved a total of 196 consecutive young (age ≤ 55 years) patients with angiographically proven CAD and 188 age-matched non-CAD individuals as controls. Traditional risk factors were evaluated using conventional assays, and levels of suPAR were measured by sandwich enzyme-linked immunosorbent assays. Results. Levels of suPAR were significantly correlated with age (, ), smoking (, ), body mass index (, ), and high-sensitivity C-reactive protein (hs-CRP; , ). Multivariate logistic regression analysis showed that male sex (odds ratio (OR) = 3.12; 95% confidence interval (CI) = 1.18–8.25, ), smoking (OR = 3.41, 95% CI = 1.55–7.50, ), triglyceride (OR = 1.89, 95% CI = 1.10–3.25, ), high-sensitivity C-reactive protein (OR = 1.24, 95% CI = 1.02–0.03, ), and suPAR (OR = 1.37, 95% CI = 1.09–1.72, ) were independently associated with CAD risk in young patients. Conclusions. SuPAR is a novel independent risk factor for CAD in young Chinese patients. Further studies evaluating the effect of anti-inflammatory treatment on the suPAR levels and the risk of CAD are needed. Yuli Huang, Haobin Zhou, Yu Wu, You Yang, Wensheng Li, Jianhua Lu, and Yunzhao Hu Copyright © 2017 Yuli Huang et al. All rights reserved. The Role of Hematological Indices in Patients with Acute Coronary Syndrome Tue, 03 Oct 2017 06:18:35 +0000 http://www.hindawi.com/journals/dm/2017/3041565/ An increased systemic and local inflammation plays a key role in the pathophysiology of acute coronary syndrome (ACS). This review will discuss the role of hematological indices: white blood cells (WBC), neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), and platelet indices, that is, platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), and platelet distribution width (PDW) in the case of ACS. In recent years, a strong interest has been drawn to these indices, given that they may provide independent information on pathophysiology, risk stratification, and optimal management. Their low-cost and consequent wide and easy availability in daily clinical practice have made them very popular in the laboratory testing. Furthermore, many studies have pointed at their effective prognostic value in all-cause mortality, major cardiovascular events, stent thrombosis, arrhythmias, and myocardial perfusion disorders in terms of acute myocardial infarction and unstable angina. The most recent research also emphasizes their significant value in the combined analysis with other markers, such as troponin, or with GRACE, SYNTAX, and TIMI scores, which improve risk stratification and diagnosis in ACS patients. Jan Budzianowski, Konrad Pieszko, Paweł Burchardt, Janusz Rzeźniczak, and Jarosław Hiczkiewicz Copyright © 2017 Jan Budzianowski et al. All rights reserved. Upregulation of FBXW7 Suppresses Renal Cancer Metastasis and Epithelial Mesenchymal Transition Sat, 30 Sep 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/8276939/ Background and Objective. FBXW7, known as a general tumor suppressor, is commonly lowly expressed in metastatic malignancies. We aim to investigate the potential influence of FBXW7 overexpression on renal cell carcinoma (RCC) metastasis. Methods. We employed quantitative real-time PCR (qRT-PCR) and Western blotting (WB) to quantify the FBXW7 expression in RCC cell lines. Upregulation of FBXW7 was performed in vitro on RCC cells using the lentivirus covering coding region FBXW7 cDNA sequence, and functional tests were performed to verify FBXW7 overexpression on migration and invasion of RCC cells. Moreover, WB was employed to determine the expressions of MMP-2, MMP-9, and MMP-13, as well as EMT markers in the transfected RCC cells. Results. FBXW7 was significantly downregulated in RCC cell lines, dominated by 786-O and ACHN, when compared to normal renal cell line HK-2. Moreover, upregulation of FBXW7 in 786-O and ACHN cell lines significantly inhibited cell migration and invasion, as well as EMT. Present study also showed that FBXW7 was involved in the migration and invasion of RCC cells via regulating the expressions of MMP-2, MMP-9, and MMP-13. Conclusion. Our findings demonstrate that upregulation of FBXW7 inhibits RCC metastasis and EMT. FBXW7 is a potential therapeutic target for RCC patients. Yangke Cai, Meng Zhang, Xiaofu Qiu, Bingwei Wang, Yu Fu, Jun Zeng, Jian Bai, and Guosheng Yang Copyright © 2017 Yangke Cai et al. All rights reserved. Relationship between rs854560 PON1 Gene Polymorphism and Tobacco Smoking with Coronary Artery Disease Fri, 29 Sep 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/1540949/ Paraoxonase-1 (PON1) is the antioxidant marker of high-density lipoproteins protecting against atherosclerosis and coronary artery disease (CAD) phenotype. The purpose of the present study was to determine whether the PON1 gene rs854560 polymorphism (163T>A) is associated with CAD in Polish population. rs854560 was genotyped in 494 subjects: 248 patients with premature CAD and 246 blood donors as a control. We found that the risk of CAD was significantly higher in TT homozygotes than in A allele carriers (OR = 1.87, ). The synergistic effect between the TT genotype and cigarette smoking was observed (SIM = 9.81; SI = 14.70). The relative increase in risk from interaction between factors was over 37 (RERI = 36.13). The PON1 polymorphism did not modulate the risk of CAD in response to exposure to other traditional risk factors. In conclusion, the rs854560 polymorphism may modulate the risk of CAD in response to cigarette smoking in Polish population. Carriers of TT genotype seem to be particularly at risk of CAD, when exposed to cigarette smoking. Joanna Iwanicka, Tomasz Iwanicki, Paweł Niemiec, Tomasz Nowak, Jolanta Krauze, Władysław Grzeszczak, Sylwia Górczyńska-Kosiorz, Anna Ochalska-Tyka, and Iwona Żak Copyright © 2017 Joanna Iwanicka et al. All rights reserved. Clinical Relevance of NGAL/MMP-9 Pathway in Patients with Endometrial Cancer Wed, 27 Sep 2017 06:45:47 +0000 http://www.hindawi.com/journals/dm/2017/6589262/ The objectives of the study were to assess the relationship between the serum levels of MMP-9 and NGAL and the clinical staging and histopathological grade of the tumor. Lipocalin-2/NGAL and MMP-9 concentrations were quantified in serum by multiplex fluorescent bead-based immunoassays (Luminex Corporation, Austin, TX, USA). The AUC values for NGAL and MMP-9 were 0.9 and 0.78, respectively. The diagnostic potential of NGAL and MMP-9 in differentiating high-stage (FIGO III and IV) and low-stage (FIGO I and II) cancer and predicting the cell differentiation grade (G1 versus G3) on the basis of the analyses of AUC values was determined to be 0.91 and 0.79 for NGAL and 0.82 and 0.84 for MMP-9, respectively. Multifactorial logistic regression analysis in the final method revealed that NGAL and MMP-9 variables were independent of the endometrial cancer risk. OR values for NGAL and MMP-9 were 1.23 (95% CI 1.421–3.27; ) and 1.09 (95% CI: 1.38–4.12; ), respectively. The NGAL/MMP-9 complex may be useful in the assessment of tumor stage before surgical treatment. Aneta Cymbaluk-Płoska, Anita Chudecka-Głaz, Ewa Pius-Sadowska, Agnieszka Sompolska-Rzechuła, Karolina Chudecka, Michał Bulsa, Bogusław Machaliński, and Janusz Menkiszak Copyright © 2017 Aneta Cymbaluk-Płoska et al. All rights reserved. LncRNA NEAT1 Regulates Cell Viability and Invasion in Esophageal Squamous Cell Carcinoma through the miR-129/CTBP2 Axis Mon, 25 Sep 2017 07:57:56 +0000 http://www.hindawi.com/journals/dm/2017/5314649/ Background. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) was reported to be aberrantly upregulated and promote esophageal squamous cell carcinoma (ESCC) cell progression. Nevertheless, the molecular mechanism of NEAT1 involved in the competing endogenous RNA (ceRNA) regulatory network in ESCC progression remains poorly defined. Methods. The expressions of NEAT1, miR-129, and C-terminal-binding protein 2 (CTBP2) in ESCC cells were examined by qRT-PCR. The effects of NEAT1 knockdown and miR-129 overexpression, or along with CTBP2 upregulation, on ESCC cell viability and invasion were explored by CCK-8 and transwell invasion assays, respectively. Luciferase reporter assay in combination with RIP was performed to confirm the interaction between NEAT1, miR-129, and CTBP2. Results. NEAT1 and CTBP2 were upregulated and miR-129 was downregulated in ESCC cells. Either NEAT1 knockdown or miR-129 overexpression suppressed ESCC cell viability and invasion. Moreover, NEAT1 functioned as an endogenous sponge to downregulate miR-129 by competitively binding to miR-129, thereby leading to the derepression of CTBP2, a target of miR-129. CTBP2 restoration overturned cell viability and invasion suppression mediated by NEAT1 knockdown or miR-129 overexpression. Conclusion. LncRNA NEAT1 regulated ESCC cell viability and invasion via the miR-129/CTBP2 axis, contributing to the better understanding of the molecular mechanism of ESCC pathogenesis and progression. Yong Li, Dong Chen, Xiang Gao, Xiaohui Li, and Gongning Shi Copyright © 2017 Yong Li et al. All rights reserved. Corrigendum to “Peritumoral EpCAM Is an Independent Prognostic Marker after Curative Resection of HBV-Related Hepatocellular Carcinoma” Wed, 20 Sep 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/3765279/ Xiao-Meng Dai, Tao Huang, Sheng-Li Yang, Xiu-Mei Zheng, George G. Chen, and Tao Zhang Copyright © 2017 Xiao-Meng Dai et al. All rights reserved. Validation of a Machine Learning Approach for Venous Thromboembolism Risk Prediction in Oncology Sun, 17 Sep 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/8781379/ Using kernel machine learning (ML) and random optimization (RO) techniques, we recently developed a set of venous thromboembolism (VTE) risk predictors, which could be useful to devise a web interface for VTE risk stratification in chemotherapy-treated cancer patients. This study was designed to validate a model incorporating the two best predictors and to compare their combined performance with that of the currently recommended Khorana score (KS). Age, sex, tumor site/stage, hematological attributes, blood lipids, glycemic indexes, liver and kidney function, BMI, performance status, and supportive and anticancer drugs of 608 cancer outpatients were all entered in the model, with numerical attributes analyzed as continuous values. VTE rate was 7.1%. The VTE risk prediction performance of the combined model resulted in 2.30 positive likelihood ratio (+LR), 0.46 negative LR (−LR), and 4.88 HR (95% CI: 2.54–9.37), with a significant improvement over the KS [HR 1.73 (95% CI: 0.47–6.37)]. These results confirm that a ML approach might be of clinical value for VTE risk stratification in chemotherapy-treated cancer outpatients and suggest that the ML-RO model proposed could be useful to design a web service able to provide physicians with a graphical interface helping in the critical phase of decision making. Patrizia Ferroni, Fabio M. Zanzotto, Noemi Scarpato, Silvia Riondino, Fiorella Guadagni, and Mario Roselli Copyright © 2017 Patrizia Ferroni et al. All rights reserved. The Prognostic Value of Decreased KLF4 in Digestive System Cancers: A Meta-Analysis from 17 Studies Thu, 14 Sep 2017 07:34:28 +0000 http://www.hindawi.com/journals/dm/2017/3064246/ Background. The prognostic value of loss of Krüppel-like factor 4 (KLF4) expression in digestive system cancers has not reached a consensus. This study aimed for a comprehensive investigation of the internal associations between KLF4 expression loss and prognostic implications in patients with digestive system cancers. Methods. We searched for all relevant literatures in the electronic databases until February 1, 2017. The degree of association between KLF4 and prognosis was evaluated by pooled hazard ratios (HRs) as well as relevant 95% confidence intervals (95% CIs). Results. Seventeen eligible studies with 2118 patients revealed that loss of KLF4 expression was connected with poor prognosis, with the pooled HRs of 1.61 (95% CI: 1.17–2.20, ) for the overall survival (OS) and 1.99 (95% CI: 1.12–3.52, ) for the disease-free survival (DFS)/recurrence-free survival (RFS)/metastasis-free survival (MFS). Additionally, loss of KLF4 expression was also related to a worse disease-special survival (DSS) yielding a pooled HR of 1.73 (95% CI: 1.08–2.77, ). Conclusion. Our findings suggest that loss of KLF4 expression is correlated with a bad outcome in most digestive system cancers, apart from esophagus squamous cell carcinoma (ESCC). Jianpei Hu, Huipu Li, Chunyu Wu, Xueying Zhao, and Chaodong Liu Copyright © 2017 Jianpei Hu et al. All rights reserved. Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma Tue, 12 Sep 2017 09:28:42 +0000 http://www.hindawi.com/journals/dm/2017/8069529/ Background. Malignant pleural mesothelioma (MPM) is a rare disease with a relatively short overall survival (OS). Metalloproteinases (MMPs) have a vast biological effect on tumor progression, invasion, metastasis formation, and apoptosis. MMP expression was previously associated with survival in MPM. Our aim was to evaluate if genetic variability of MMP genes could also serve as a prognostic biomarker in MPM. Methods. We genotyped 199 MPM patients for ten polymorphisms: rs243865, rs243849 and rs7201, in MMP2; rs17576, rs17577, rs20544, and rs2250889 in MMP9; and rs1042703, rs1042704, and rs743257 in MMP14. We determined the influence on survival using Cox regression. Results. Carriers of polymorphic MMP9 rs2250889 allele had shorter time to progression (TTP) (6.07 versus 10.03 months, HR = 2.45, 95% CI = 1.45–4.14, ) and OS (9.23 versus 19.2 months, HR = 2.39, 95% CI = 1.37–4.18, ). In contrast, carriers of at least one polymorphic MMP9 rs20544 allele had longer TTP (10.93 versus 9.40 months, HR = 0.57, 95% CI = 0.38–0.86 ) and OS (20.67 versus 13.50 months, HR = 0.56, 95% CI = 0.37–0.85, ). MMP14 rs1042703 was associated with nominally shorter TTP (8.7 versus 9.27 months, HR = 2.09, 95% CI = 1.06–4.12, ). Conclusions. Selected MMP SNPs were associated with survival and could be used as potential genetic biomarkers in MPM. Danijela Štrbac, Katja Goričar, Vita Dolžan, and Viljem Kovač Copyright © 2017 Danijela Štrbac et al. All rights reserved. The Predictive Value of PITX2 DNA Methylation for High-Risk Breast Cancer Therapy: Current Guidelines, Medical Needs, and Challenges Tue, 12 Sep 2017 07:14:43 +0000 http://www.hindawi.com/journals/dm/2017/4934608/ High-risk breast cancer comprises distinct tumor entities such as triple-negative breast cancer (TNBC) which is characterized by lack of estrogen (ER) and progesterone (PR) and the HER2 receptor and breast malignancies which have spread to more than three lymph nodes. For such patients, current (inter)national guidelines recommend anthracycline-based chemotherapy as the standard of care, but not all patients do equally benefit from such a chemotherapy. To further improve therapy decision-making, predictive biomarkers are of high, so far unmet, medical need. In this respect, predictive biomarkers would permit patient selection for a particular kind of chemotherapy and, by this, guide physicians to optimize the treatment plan for each patient individually. Besides DNA mutations, DNA methylation as a patient selection marker has received increasing clinical attention. For instance, significant evidence has accumulated that methylation of the PITX2 (paired-like homeodomain transcription factor 2) gene might serve as a novel predictive and prognostic biomarker, for a variety of cancer diseases. This review highlights the current understanding of treatment modalities of high-risk breast cancer patients with a focus on recommended treatment options, with special attention on the future clinical application of PITX2 as a predictive biomarker to personalize breast cancer management. Michaela Aubele, Manfred Schmitt, Rudolf Napieralski, Stefan Paepke, Johannes Ettl, Magdalena Absmaier, Viktor Magdolen, John Martens, John A. Foekens, Olaf G. Wilhelm, and Marion Kiechle Copyright © 2017 Michaela Aubele et al. All rights reserved. Longitudinal Assessment of Transorbital Sonography, Visual Acuity, and Biomarkers for Inflammation and Axonal Injury in Optic Neuritis Mon, 11 Sep 2017 07:21:22 +0000 http://www.hindawi.com/journals/dm/2017/5434310/ Background and Objective. To investigate the relationship between optic nerve sheath diameter, optic nerve diameter, visual acuity and osteopontin, and neurofilament heavy chain in patients with acute optic neuritis. Patients and Methods. Sonographic and visual acuity assessment and biomarker measurements were executed in 23 patients with unilateral optic neuritis and in 19 sex- and age-matched healthy controls. Results. ONSD was thicker on the affected side at symptom onset (median 6.3 mm; interquartile range 6.0–6.5) than after 12 months (5.3 mm; 4.9–5.6; ) or than in controls (5.2 mm; 4.8–5.5; ). OND was significantly increased in the affected side (3.4 mm; 2.9–3.8) compared to healthy controls (2.7 mm; 2.5–2.9; ) and was thicker at baseline than after 12 months (2.8 mm; 2.7–3.0; ). Visual acuity improved significantly after 12 months (1.00; 0.90–1.00) compared to onset of symptoms (0.80; 0.40–1.00; ). OPN levels were significantly higher in patients at presentation (median 6.44 ng/ml; 2.05–10.06) compared to healthy controls (3.21 ng/ml, 1.34–4.34; ). Concentrations of NfH were significantly higher in patients than in controls. Conclusion. ONSD and OND are increased in the affected eye. OPN and NfH are elevated in patients, confirming the presence of any underlying inflammation and axonal injury. Piergiorgio Lochner, Roberto Cantello, Klaus Fassbender, Martin Lesmeister, Raffaele Nardone, Antonio Siniscalchi, Nausicaa Clemente, Andrea Naldi, Lorenzo Coppo, Francesco Brigo, and Cristoforo Comi Copyright © 2017 Piergiorgio Lochner et al. All rights reserved. Malignant Mesothelioma, BAP1 Immunohistochemistry, and VEGFA: Does BAP1 Have Potential for Early Diagnosis and Assessment of Prognosis? Mon, 11 Sep 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/1310478/ Malignant mesothelioma (MM) is an aggressive malignancy of the serosal membranes. Early diagnosis and accurate prognostication remain problematic. BAP1 is a tumour suppressor gene commonly mutated in MM. Germline BAP1 mutation has been associated with early onset and less aggressive disease compared with sporadic MM. Sporadic BAP1 mutations are common and are associated with improved survival in MM, contrary to other malignancies. This study investigated the prognostic role of BAP1 in matched cytology and surgical specimens and aimed to investigate the association between BAP1 and the established prognostic marker VEGFA from a cohort of 81 patients. BAP1 mutation was found in 58% of histology and 59% of cytology specimens. Loss of BAP1 expression in both surgical and cytology specimens was significantly associated with poorer survival in a multivariate analysis when controlling for known prognostic indicators. Increased levels of VEGFA in pleural effusions were associated with poor survival. We conclude that the prognostic significance of BAP1 mutations in MM cannot be determined in isolation of other prognostic factors, which may vary between patients. Pathologists should employ caution when commenting on prognostic implications of BAP1 status of MM patients in diagnostic pathology reports, but it may be useful for early diagnosis. Emily Pulford, Kalyani Huilgol, David Moffat, Douglas W. Henderson, and Sonja Klebe Copyright © 2017 Emily Pulford et al. All rights reserved. DNA Methylation Events as Markers for Diagnosis and Management of Acute Myeloid Leukemia and Myelodysplastic Syndrome Wed, 06 Sep 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/5472893/ During the onset and progression of hematological malignancies, many changes occur in cellular epigenome, such as hypo- or hypermethylation of CpG islands in promoter regions. DNA methylation is an epigenetic modification that regulates gene expression and is a key event for tumorigenesis. The continuous search for biomarkers that signal early disease, indicate prognosis, and act as therapeutic targets has led to studies investigating the role of DNA in cancer onset and progression. This review focuses on DNA methylation changes as potential biomarkers for diagnosis, prognosis, response to treatment, and early toxicity in acute myeloid leukemia and myelodysplastic syndrome. Here, we report that distinct changes in DNA methylation may alter gene function and drive malignant cellular transformation during several stages of leukemogenesis. Most of these modifications occur at an early stage of disease and may predict myeloid/lymphoid transformation or response to therapy, which justifies its use as a biomarker for disease onset and progression. Methylation patterns, or its dynamic change during treatment, may also be used as markers for patient stratification, disease prognosis, and response to treatment. Further investigations of methylation modifications as therapeutic biomarkers, which may correlate with therapeutic response and/or predict treatment toxicity, are still warranted. Geórgia Muccillo Dexheimer, Jayse Alves, Laura Reckziegel, Gabrielle Lazzaretti, and Ana Lucia Abujamra Copyright © 2017 Geórgia Muccillo Dexheimer et al. All rights reserved. Red Blood Cell Distribution Width: A Novel Predictive Indicator for Cardiovascular and Cerebrovascular Diseases Wed, 06 Sep 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/7089493/ The red blood cell distribution width (RDW) obtained from a standard complete blood count (CBC) is a convenient and inexpensive biochemical parameter representing the variability in size of circulating erythrocytes. Over the past few decades, RDW with mean corpuscular volume (MCV) has been used to identify quite a few hematological system diseases including iron-deficiency anemia and bone marrow dysfunction. In recent years, many clinical studies have proved that the alterations of RDW levels may be associated with the incidence and prognosis in many cardiovascular and cerebrovascular diseases (CVDs). Therefore, early detection and intervention in time of these vascular diseases is critical for delaying their progression. RDW as a new predictive marker and an independent risk factor plays a significant role in assessing the severity and progression of CVDs. However, the mechanisms of the association between RDW and the prognosis of CVDs remain unclear. In this review, we will provide an overview of the representative literatures concerning hypothetical and potential epidemiological associations between RDW and CVDs and discuss the underlying mechanisms. Ning Li, Heng Zhou, and Qizhu Tang Copyright © 2017 Ning Li et al. All rights reserved. Expression of AdipoR1 and AdipoR2 Receptors as Leptin-Breast Cancer Regulation Mechanisms Tue, 05 Sep 2017 09:45:49 +0000 http://www.hindawi.com/journals/dm/2017/4862016/ The development of breast cancer is influenced by the adipose tissue through the proteins leptin and adiponectin. However, there is little research concerning AdipoR1 and AdipoR2 receptors and the influence of leptin over them. The objective of this work was to analyze the expression of AdipoR1 and AdipoR2, modulated by differential concentrations of leptin in an obesity model (10 ng/mL, 100 ng/mL, and 1000 ng/mL) associated with breast cancer in MCF-7 and HCC1937 cell lines. Each cell line was characterized through immunohistochemistry, and the expression of AdipoR1 and AdipoR2 was analyzed by PCR in real time using TaqMan® probes. Leptin induced an increase in cell population of MCF-7 (23.8%, 10 ng/mL, 48 h) and HCC1937 (17.24%, 1000 ng/mL, 72 h). In MCF-7, the expression of AdipoR1 decreased (3.81%, 1000 ng/mL) and the expression of AdipoR2 increased by 13.74 times (10 ng/mL) with regard to the control. In HCC1937, the expression of AdipoR1 decreased by 86.28% (10 ng/mL), as well as the expression of AdipoR2 (50.3%, 100 ng/mL). In regard to the results obtained, it could be concluded that leptin has an effect over the expression of AdipoR1 and AdipoR2 mRNA. Martha Daniela Mociño-Rodríguez, Jonnathan Guadalupe Santillán-Benítez, David Salomón Dozal-Domínguez, María Dolores Hernández-Navarro, Miriam Veronica Flores-Merino, Antonio Sandoval-Cabrera, and Francisco Javier García Vázquez Copyright © 2017 Martha Daniela Mociño-Rodríguez et al. All rights reserved. Nasal Cytology as a Marker of Atopy in Children Tue, 05 Sep 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/4159251/ The aim of this study was to evaluate the cytological picture of nasal mucosa in children with atopic diseases and to determine the diagnostic value of the test for the diagnosis of atopic diseases. The study included 140 children from 4 months to 17 years old. Among children with a history of atopy, there were 30 children with atopic dermatitis, 30 children with asthma, and 46 children with allergic rhinitis. The control group consisted of 34 healthy children. The nasal scraping technique has been used to collect samples from the nasal cavity. The samples were evaluated under light microscope. Epithelial cells as well as infiltrating cells were assessed. The only statistically significant group of cells differentiating children with atopic disease and without atopy were eosinophils, which in children with atopy were significantly more common. Assuming a significant eosinophilia value of at least 5% of all cells in cytogram, the sensitivity of nasal cytology in allergic rhinitis was 52.2%, in asthma 33.3%, and in atopic dermatitis 13.3%. The specificity of the test in atopic diseases was 94.1%. It can be concluded that nasal cytology with eosinophilia assessment can be a useful tool for an early diagnosis of atopic disease in children. Anna Mierzejewska, Anna Jung, and Bolesław Kalicki Copyright © 2017 Anna Mierzejewska et al. All rights reserved. DNA Methylation as a Noninvasive Epigenetic Biomarker for the Detection of Cancer Tue, 05 Sep 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/3726595/ In light of the high incidence and mortality rates of cancer, early and accurate diagnosis is an important priority for assigning optimal treatment for each individual with suspected illness. Biomarkers are crucial in the screening of patients with a high risk of developing cancer, diagnosing patients with suspicious tumours at the earliest possible stage, establishing an accurate prognosis, and predicting and monitoring the response to specific therapies. Epigenetic alterations are innovative biomarkers for cancer, due to their stability, frequency, and noninvasive accessibility in bodily fluids. Epigenetic modifications are also reversible and potentially useful as therapeutic targets. Despite this, there is still a lack of accurate biomarkers for the conclusive diagnosis of most cancer types; thus, there is a strong need for continued investigation to expand this area of research. In this review, we summarise current knowledge on methylated DNA and its implications in cancer to explore its potential as an epigenetic biomarker to be translated for clinical application. We propose that the identification of biomarkers with higher accuracy and more effective detection methods will enable improved clinical management of patients and the intervention at early-stage disease. Catherine Leygo, Marissa Williams, Hong Chuan Jin, Michael W. Y. Chan, Wai Kit Chu, Michael Grusch, and Yuen Yee Cheng Copyright © 2017 Catherine Leygo et al. All rights reserved. Risk Factors for the Development of Refeeding Syndrome-Like Hypophosphatemia in Very Low Birth Weight Infants Tue, 05 Sep 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/9748031/ Background. Refeeding syndrome is characterized by metabolic disturbance including hypophosphatemia and hypokalemia upon reinstitution of nutrition in severely malnourished patients. Objective. The present study sought to identify the risk factors for the development of refeeding syndrome-like metabolic disturbance in very low birth weight infants. Methods. The correlations of severe hypophosphatemia with the serum levels of potassium and ionized calcium, daily calorie and phosphate intake, and umbilical cord blood flow on ultrasonography were analyzed in 49 very low birth weight infants. Results. Fifteen infants (36%) presented with hypophosphatemia during the first postnatal week. Hypophosphatemia was significantly associated with birth weight z score (odds ratio, 1.60; 95% confidence interval, 1.04–2.47; ) and umbilical artery resistance index (odds ratio, 7.72E−04; 95% confidence interval, 1.14E−06–0.523; ). Multiple regression analysis revealed that umbilical artery resistance index was independently associated with hypophosphatemia. Conclusions. Umbilical artery resistance index may serve as a useful marker for future development of refeeding syndrome-like hypophosphatemia in very low birth weight infants. Close monitoring of serum phosphorus and potassium levels and early intervention are important for the management of very low birth weight infants with intrauterine growth restriction due to placental dysfunction. Aiko Igarashi, Takashi Okuno, Genrei Ohta, Shuko Tokuriki, and Yusei Ohshima Copyright © 2017 Aiko Igarashi et al. All rights reserved. The Expression and Related Clinical Significance of SIRT3 in Non-Small-Cell Lung Cancer Wed, 30 Aug 2017 05:47:43 +0000 http://www.hindawi.com/journals/dm/2017/8241953/ Objective. To examine the relationship between the Sirtuin-3 (SIRT3) expression and the clinical indicators/prognosis of patients with non-small-cell lung cancer (NSCLC). Methods. The mRNA level of SIRT3 was detected by real-time PCR, while the protein level was detected by Western blot and immunohistochemical staining. SPSS 16.0 software was used for statistical analysis. Results. The expression of SIRT3 was significantly higher in NSCLC tissue than in adjacent tissue. The SIRT3 level was correlated significantly with lymph node metastasis and clinical stage of NSCLC patients. Moreover, univariate analysis showed that the expression of SIRT3, tumor size, lymph node metastasis, degree of differentiation, and clinical stage were correlated with the prognosis of NSCLC patients. Multivariate analysis demonstrated that lymph node metastasis, the tumor size, and SIRT3 expression were independent prognostic factors for NSCLC patients. Conclusions. SIRT3 is associated with the development and progression of NSCLC. The SIRT3 expression can be used as an independent prognostic factor for NSCLC patients and help identify prognosis of NSCLC. Therefore, SIRT3 has the potential to become a new factor for prognosis prediction and personalized treatment of NSCLC. Guo-Cai Yang, Bi-Cheng Fu, Dong-Yang Zhang, Lu Sun, Wei Chen, Long Bai, Tong Gao, Hong-Guang Lu, Zhao-Yu Wang, Qiong-Qiong Kong, Lin Qiu, and Hai Tian Copyright © 2017 Guo-Cai Yang et al. All rights reserved. Identification of Biomarkers for Predicting Lymph Node Metastasis of Stomach Cancer Using Clinical DNA Methylation Data Tue, 29 Aug 2017 07:27:18 +0000 http://www.hindawi.com/journals/dm/2017/5745724/ Background. Lymph node (LN) metastasis was an independent risk factor for stomach cancer recurrence, and the presence of LN metastasis has great influence on the overall survival of stomach cancer patients. Thus, accurate prediction of the presence of lymph node metastasis can provide guarantee of credible prognosis evaluation of stomach cancer patients. Recently, increasing evidence demonstrated that the aberrant DNA methylation first appears before symptoms of the disease become clinically apparent. Objective. Selecting key biomarkers for LN metastasis presence prediction for stomach cancer using clinical DNA methylation based on a machine learning method. Methods. To reduce the overfitting risk of prediction task, we applied a three-step feature selection method according to the property of DNA methylation data. Results. The feature selection procedure extracted several cancer-related and lymph node metastasis-related genes, such as TP73, PDX1, FUT8, HOXD1, NMT1, and SEMA3E. The prediction performance was evaluated on the public DNA methylation dataset. The results showed that the three-step feature procedure can largely improve the prediction performance and implied the reliability of the biomarkers selected. Conclusions. With the selected biomarkers, the prediction method can achieve higher accuracy in detecting LN metastasis and the results also proved the reliability of the selected biomarkers indirectly. Jun Wu, Yawen Xiao, Chao Xia, Fan Yang, Hua Li, Zhifeng Shao, Zongli Lin, and Xiaodong Zhao Copyright © 2017 Jun Wu et al. All rights reserved. Diagnostic Value of the Methylation of Multiple Gene Promoters in Serum in Hepatitis B Virus-Related Hepatocellular Carcinoma Tue, 29 Aug 2017 06:17:28 +0000 http://www.hindawi.com/journals/dm/2017/2929381/ This study sought to evaluate the diagnostic value of the methylation of multiple gene promoters in serum in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). A total of 343 participants were enrolled, including 98 patients with HCC, 75 patients with liver cirrhosis (LC), 90 patients with chronic hepatitis B (CHB), and 80 healthy individuals. RASSF1A, APC, BVES, TIMP3, GSTP1, and HOXA9 were selected as the candidate genes. The MethyLight method was used to assay promoter methylation statuses. The diagnostic performances of markers were assessed by constructing receiver operating characteristic (ROC) curves. The prevalences of methylation for RASSF1A, APC, BVES, HOXA9, GSTP1, and TIMP3 were 52.04%, 36.73%, 29.59%, 20.41%, 17.35%, and 11.22%, respectively. APC methylation completely overlapped with RASSF1A methylation. The area under the curve (AUC) for RASSF1A methylation (0.718) was better than the corresponding AUC for AFP (0.609) in distinguishing HCC from CHB. When RASSF1A, BVES, HOXA9, and AFP were combined, the AUC was 0.852 (95% CI = 0.796–0.908, ), and the sensitivity and specificity were 83.7% and 78.9%, respectively. In conclusion, an assay that combines methylation of the RASSF1A, BVES, and HOXA9 gene promoters in serum and AFP could significantly improve HBV-related HCC diagnoses. Xueyan Dong, Qiang Hou, Yueming Chen, and Xianjun Wang Copyright © 2017 Xueyan Dong et al. All rights reserved. Adiponectin, Retinoic Acid Receptor Responder 2, and Peroxisome Proliferator-Activated Receptor-γ Coativator-1 Genes and the Risk for Obesity Tue, 29 Aug 2017 04:07:29 +0000 http://www.hindawi.com/journals/dm/2017/5289120/ Obesity is the most common nutritional disorder. This disease is a multifactorial disease influenced by environmental and genetic factors. This study investigated the relationship between common variants of adiponectin (ADIPOQ), retinoic acid receptor responder 2 (RARRES2), and peroxisome proliferator-activated receptor-γ coativator-1 (PPARGC1) and obesity-related traits and susceptibility. A total of 167 individuals with obesity and 165 normal-weight subjects were recruited. Genotype frequencies of rs182052 in ADIPOQ differed significantly between the groups. Genotype AA was observed at a higher frequency in case than in control subjects. Association analysis showed that the A allele was a risk factor for obesity. This polymorphism was associated with body weight, body mass index (BMI), and waist circumference. After stratification by BMI, eutrophic individuals with AA or AG genotypes had higher body weights and waist circumferences than those with GG genotypes. In the case group, no associations were observed, except for stratified subjects with morbid obesity that exhibited a progressive increase of body weight, BMI, and waist circumference when rs182052 A was present. No associations were observed between SNPs in RARRES2 and PPARGC1 and obesity or any other studied variables. The rs182052 polymorphism in ADIPOQ is associated with a higher risk for obesity and obesity-related parameters. Ana Carolina Proença da Fonseca, Alan Cleveland Ochioni, Raisa da Silva Martins, Verônica Marques Zembrzuski, Mario Campos Junior, Vivianne Galante Ramos, João Regis Ivar Carneiro, José Firmino Nogueira Neto, Pedro Hernan Cabello, and Giselda Maria Kalil Cabello Copyright © 2017 Ana Carolina Proença da Fonseca et al. All rights reserved. Angiopoietin-2 Levels as Predictors of Outcome in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome Tue, 29 Aug 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/6758721/ Pulmonary endothelium dysfunction is a key characteristic of ARDS. The aim of this study was to investigate endothelium-derived markers, such as angiopoietin-2 (Ang-2) and endothelial cell-specific molecule-1 (endocan), at the vascular and alveolar compartments as outcome predictors in ARDS. Fifty-three consecutive ARDS patients were studied. The primary outcome was 28-day mortality. Secondary endpoints were days of unassisted ventilation and days with organ failure other than ARDS, during the 28-day study period. Nonsurvivors presented higher lung injury scores and epithelial lining fluid (ELF) Ang-2 levels compared to survivors, with no significant differences in plasma Ang-2, endocan, and protein C concentrations between the two groups. In logistic regression analysis, ELF Ang-2 levels > 705 pg/ml were the only independent variable for 28-day mortality among the previous four. Plasma endocan values > 13 ng/pg were the only parameter predictive against days of unassisted ventilation during the 28-day study period. Finally, lung injury score > 2.25 and ELF Ang-2 levels > 705 pg/ml were associated with increased number of days with organ failure, other than ARDS. Our findings suggest that Ang-2 levels are increased in the alveolar compartment of ARDS patients, and this may be associated both with increased mortality and organ failure besides lung. Iraklis Tsangaris, Argirios Tsantes, Eleni Vrigkou, Petros Kopterides, Aimilia Pelekanou, Katerina Zerva, George Antonakos, Dimitrios Konstantonis, Irini Mavrou, Georgios Tsaknis, Evdoxia Kyriazopoulou, Maria Mouktaroudi, Styliani Kokori, Stylianos E. Orfanos, Evangelos J. Giamarellos-Bourboulis, and Apostolos Armaganidis Copyright © 2017 Iraklis Tsangaris et al. All rights reserved. Polymorphisms in lncRNA PTENP1 and the Risk of Gastric Cancer in a Chinese Population Mon, 28 Aug 2017 07:21:39 +0000 http://www.hindawi.com/journals/dm/2017/6807452/ Long noncoding RNA (lncRNA) phosphatase and tensin homolog pseudogene 1 (PTENP1) is significantly downregulated in gastric cancer (GC), playing critical roles in GC progression. However, the association between PTENP1 genetic variants and GC risk has not yet been reported. Using TaqMan technology, three lncRNA PTENP1 tag single nucleotide polymorphisms (tagSNPs) (rs7853346 C>G, rs865005 C>T, and rs10971638 G>A) were genotyped in 768 GC patients and 768 cancer-free controls in a Chinese population. We found that subjects with rs7853346 G allele had a remarkably decreased risk of GC, compared with those carrying C allele ( in an additive model, after Bonferroni’s correction). The further stratified analyses showed that the link between variant genotypes of rs7853346 and decreased GC risk was more obvious in older subjects (≥60 years), nonsmokers, nondrinkers, and subjects without family history of GC. We also found that relative PTENP1 mRNA expression levels were higher in rs7853346 CG/GG genotype carriers than those with common genotype in both GC and normal tissues (). Besides, bioinformatics analyses revealed that rs7853346 may change the local folding structure and alter the target microRNAs (miRNAs) of PTENP1. In conclusion, our results suggested that lncRNA PTENP1 polymorphism rs7853346 may predict GC susceptibility. Yugang Ge, Yu He, Mingkun Jiang, Dakui Luo, Xiangkun Huan, Weizhi Wang, Diancai Zhang, Li Yang, and Jundong Zhou Copyright © 2017 Yugang Ge et al. All rights reserved.