Disease Markers https://www.hindawi.com The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. A Promising Approach to Integrally Evaluate the Disease Outcome of Cerebral Ischemic Rats Based on Multiple-Biomarker Crosstalk Thu, 25 May 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/9506527/ Purpose. The study was designed to evaluate the disease outcome based on multiple biomarkers related to cerebral ischemia. Methods. Rats were randomly divided into sham, permanent middle cerebral artery occlusion, and edaravone-treated groups. Cerebral ischemia was induced by permanent middle cerebral artery occlusion surgery in rats. To form a simplified crosstalk network, the related multiple biomarkers were chosen as S100β, HIF-1α, IL-1β, PGI2, TXA2, and GSH-Px. The levels or activities of these biomarkers in plasma were detected before and after ischemia. Concurrently, neurological deficit scores and cerebral infarct volumes were assessed. Based on a mathematic model, network balance maps and three integral disruption parameters (k, φ, and u) of the simplified crosstalk network were achieved. Results. The levels or activities of the related biomarkers and neurological deficit scores were significantly impacted by cerebral ischemia. The balance maps intuitively displayed the network disruption, and the integral disruption parameters quantitatively depicted the disruption state of the simplified network after cerebral ischemia. The integral disruption parameter u values correlated significantly with neurological deficit scores and infarct volumes. Conclusion. Our results indicate that the approach based on crosstalk network may provide a new promising way to integrally evaluate the outcome of cerebral ischemia. Guimei Ran, Yixuan Wang, Haochen Liu, Chunxiang Wei, Tao Zhu, Haidong Wang, Hua He, and Xiaoquan Liu Copyright © 2017 Guimei Ran et al. All rights reserved. Discriminating Value of Calprotectin in Disease Activity and Progression of Nonradiographic Axial Spondyloarthritis and Ankylosing Spondylitis Wed, 24 May 2017 06:48:03 +0000 http://www.hindawi.com/journals/dm/2017/7574147/ It has been controversial whether ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA) are separate or different phases of radiographic progression. We determined that serum calprotectin level (ng/ml) was higher in AS (15.30 ± 6.49) and nr-axSpA (17.76 ± 8.59) patients than in healthy individuals (7.40 ± 2.67). No difference was observed in calprotectin level between these two groups. Elevated calprotectin was positively correlated with ESR, CRP, BASDAI, and ASDAS as well as SPARCC scoring and had no correlation with BASFI and mSASSS. No correlation was observed between calprotectin and Wnt/β-catenin pathway markers. Serum calprotectin can be used as a marker for inflammation in both nr-axSpA and AS, while it does not contribute to the discrimination of AS and nr-axSpA. Calprotectin-mediated inflammation was not correlated with principle effectors of Wnt/β-catenin pathway, indicating that inflammation and bone fusion might be separate processes of the disease. Jinxian Huang, Zhihua Yin, Guoxiang Song, Shengjin Cui, Jinzhao Jiang, and Lijun Zhang Copyright © 2017 Jinxian Huang et al. All rights reserved. CD146 Promoter Polymorphism (rs3923594) Is Associated with Recurrence of Clear Cell Renal Cell Carcinoma in Chinese Population Wed, 24 May 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/2543059/ Introduction. CD146 is a membrane signal receptor in tumor-induced angiogenesis. However, limited studies have focused on the CD146 promoter polymorphisms in clear cell renal cell carcinoma (ccRCC). Purpose. The purpose of this study was to investigate the association between polymorphisms located in the promoter region of the CD146 gene and characteristics of ccRCC in Chinese population. The association between the CD146 promoter polymorphisms and CD146 expression was also investigated in ccRCC. Materials and Methods. A total of 600 samples including 300 ccRCC patients and 300 healthy controls were collected for analysis of the CD146 promoter polymorphisms by direct sequence. The CD146 expressions were measured by qRT-PCR. Results. We had not found any significant differences in genotypic and allelic frequencies of CD146 promoter polymorphisms between ccRCC patients and controls. The rs3923594 was associated with stage and metastasis (300 cases) and recurrence (263 cases) of ccRCC in Chinese population. A significant association was also observed between the rs3923594 and CD146 expression (227 cases) in ccRCC. Conclusions. CD146 promoter polymorphisms were not associated with the risk of ccRCC in Chinese population. The rs3923594 was an independent predictor of recurrence in Chinese patients with localized ccRCC. Gang Feng, Hou-Bao Huang, Xiao-Bing Ye, Peng Zhang, Jian-Jun Huang, Li-Zhu Huang, Long Cheng, Chun Pu, and Guorong Li Copyright © 2017 Gang Feng et al. All rights reserved. EV-Associated MMP9 in High-Grade Serous Ovarian Cancer Is Preferentially Localized to Annexin V-Binding EVs Thu, 18 May 2017 08:00:50 +0000 http://www.hindawi.com/journals/dm/2017/9653194/ High-grade serous ovarian cancer (HGSOC) is the most aggressive type of ovarian cancer and is responsible for most deaths caused by gynecological cancers. Numerous candidate biomarkers were identified for this disease in the last decades, but most were not sensitive or specific enough for clinical applications. Hence, new biomarkers for HGSOC are urgently required. This study aimed to identify new markers by isolating different extracellular vesicle (EV) types from the ascites of ovarian cancer patients according to their affinities for lipid-binding proteins and analyzing their protein cargo. This approach circumvents the low signal-to-noise ratio when using biological fluids for biomarker discovery and the issue of contamination by large non-EV complexes. We isolated and analyzed three distinct EV populations from the ascites of patients with ovarian cancer or cirrhosis and observed that Annexin V-binding EVs have higher levels of matrix metalloproteinase 9 in malignant compared to portal-hypertensive ascites. As this protein was not detected in other EV populations, this study validates our approach of using different EV types for optimal biomarker discovery. Furthermore, MMP9 in Annexin V-binding EVs could be a HGSOC biomarker with enhanced specificity, because its identification requires detection of two distinct components, that is, lipid and protein. Agnes T. Reiner, Sisareuth Tan, Christiane Agreiter, Katharina Auer, Anna Bachmayr-Heyda, Stefanie Aust, Nina Pecha, Mattias Mandorfer, Dietmar Pils, Alain R. Brisson, Robert Zeillinger, and Sai Kiang Lim Copyright © 2017 Agnes T. Reiner et al. All rights reserved. Clinical Significance and Prognostic Value of the Expression of LAMP3 in Oral Squamous Cell Carcinoma Thu, 18 May 2017 04:34:15 +0000 http://www.hindawi.com/journals/dm/2017/1218254/ Recent studies demonstrated high expression of lysosome-associated membrane protein 3 (LAMP3) in a variety of malignancies including esophageal squamous cell carcinoma, gastrointestinal cancer, breast cancer, and cervical cancer and its involvement in several biological activities of tumor cells. However, the expression of LAMP3 and its value in oral squamous cell carcinoma (OSCC) remain unclear. In this study, we examined the expression of LAMP3 in OSCC tissue samples and investigated the relationship between LAMP3 and clinical characteristics of patients with OSCC. We examined mRNA and protein levels of LAMP3 in OSCC tissues and neighboring normal tissues using quantitative real-time polymerase chain reaction and immunohistochemistry analyses, respectively. Both the mRNA and protein levels of LAMP3 were significantly higher in OSCC tissues than in adjacent normal tissues. Chi-square analysis showed that the high LAMP3 expression was notably linked to the degree of tumor differentiation and advanced TNM stage. Univariate and multivariate analyses showed that the high LAMP3 expression was an independent prognostic marker in OSCC. Our results suggest that LAMP3 might act as a potential anticancer target and a prognostic marker in patients with OSCC. Jun Lu, Hengcheng Ma, Shuijin Lian, Dan Huang, Min Lian, Ye Zhang, Jianfei Huang, and Xingmei Feng Copyright © 2017 Jun Lu et al. All rights reserved. Prospective and Descriptive Study on Serum Androstenedione Concentration in Healthy Children from Birth until 18 Years of Age and Its Associated Factors Tue, 16 May 2017 07:24:22 +0000 http://www.hindawi.com/journals/dm/2017/9238304/ Introduction. Androstenedione (A4) is an adrenal and gonadal steroid biomarker, useful in the assessment of children in whom steroidogenic disorders are suspected. The first key step in the evaluation of a diagnostic test resides on confident reference intervals (RI). The lack of updated A4-RI with current methods in pediatrics may mislead A4 results and limit its diagnosis accuracy. Aim. To provide A4 reference ranges in healthy children. Methods. Prospective, descriptive study. 283 children aged 4 days to 18 years were included. In , A4 was measured directly in serum (NE-A4) and postorganic solvent extraction (E-A4) for the assessment of interfering steroids. The influence of chronological age (CA), gender, and Tanner stage (T) were investigated. Results. In the neonatal period, E-A4 was significantly lower than NE-A4; boys had higher NE-A4; sexual dimorphism disappeared after extraction procedure. In children older than 4 months, A4 concentration remained low until the age of 5 years. Thereafter, A4 increased significantly in association with CA and T (; ), obtaining the highest concentrations in children within pubertal ages without sexual dimorphism. Conclusion. We recommend to perform solvent extraction in neonates and to take into account age and sexual development to properly interpret A4 results in childhood. María Gabriela Ballerini, Virginia Gaido, María Eugenia Rodríguez, Ana Chiesa, and María Gabriela Ropelato Copyright © 2017 María Gabriela Ballerini et al. All rights reserved. A Rational Adoption of the High Sensitive Assay for Cardiac Troponin I in Diagnostic Routine Mon, 15 May 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/4523096/ We describe the adoption of high sensitive troponin I (hsTnI) in clinical practice in two hospital settings in Italy. Samples from 426 consecutive patients (mean age 68.8 ± 17.0) admitted to the Emergency Department with a suspected acute coronary syndrome (ACS) have been tested at admittance and after 3 and 6 hours by contemporary TnI and hsTnI. Results have been compared to the final clinical diagnosis. Troponin was detectable in 68.6% by TnI and 89.9% by hsTnI. Since hsTnI has a lower threshold for females, 38/41 patients with positive values only by hsTnI were women. The correlation between the assays was very high (). A diagnosis of acute myocardial infarction (AMI) was made in 45 cases (10.5%). The negative and positive predictive values for a 50% troponin variation at 3 hours were 95.8% and 66.7% for hsTnI and 95.0% and 52.6% for TnI and at 6 hours 90.3% and 100% for hsTnI and 88.9% and 78.9% for TnI, respectively. Receiver operating characteristic (ROC) curve analysis demonstrated a greater efficiency by hsTnI at 3 hours versus 6 hours (AUC = 0.91 versus 0.72). The main benefits of hsTnI are the adoption of gender-specific 99th percentile and the shortening of time to decision. Antonio Croce, Pietro Brunati, Carlo Colzani, Riccardo Terramocci, Stefano Favero, Gabriele Bordoni, and Claudio Galli Copyright © 2017 Antonio Croce et al. All rights reserved. Associations between Interleukin-31 Gene Polymorphisms and Dilated Cardiomyopathy in a Chinese Population Wed, 10 May 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/4191365/ To explore the role of Interkeulin-31 (IL-31) in dilated cardiomyopathy (DCM), in our study, two SNPs of IL-31, rs4758680 (C/A) and rs7977932 (C/G), were analyzed in 331 DCM patients and 493 controls in a Chinese Han population. The frequencies of C allele and CC genotype of rs4758680 were significantly increased in DCM patients (, , resp.). Compared to CC genotype of rs4758680, the A carriers (CA/AA genotypes) were the protect factors in DCM susceptibility while the frequencies of CA/AA genotypes were decreased in the dominant model for DCM group (, OR = 0.56, 95%CI = 0.39–0.79). Moreover, IL-31 mRNA expression level of white blood cells was increased in DCM patients (0.072 (0.044–0.144) versus 0.036 (0.020–0.052), ). In survival analysis of 159 DCM patients, Kaplan-Meier curve revealed the correlation between CC homozygote of rs4758680 and worse prognosis for DCM group (). Compared to CC genotype, the CA/AA genotypes were the independent factors in both univariate (HR = 0.530, 95%CI = 0.337–0.834, ) and multivariate analyses after age, gender, left ventricular end-diastolic diameter, and left ventricular ejection fraction adjusted (HR = 0.548, 95%CI = 0.345–0.869, ). Thus, we concluded that IL-31 gene polymorphisms were tightly associated with DCM susceptibility and contributed to worse prognosis in DCM patients. Huizi Song, Ying Peng, Bin Zhou, Nan Chen, Xiaochuan Xie, Qingyu Dou, Yue Zhong, and Li Rao Copyright © 2017 Huizi Song et al. All rights reserved. Peritumoral EpCAM Is an Independent Prognostic Marker after Curative Resection of HBV-Related Hepatocellular Carcinoma Wed, 10 May 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/8495326/ Accumulating evidence suggests that the tumor microenvironment has a profound influence on tumor initiation and progression, opening a new avenue for studying tumor biology. Nonetheless, the prognostic values of the peritumoral expression of EpCAM and CD13 remain to be elucidated in hepatocellular carcinoma (HCC) patients. In this study, the expression of EpCAM and CD13 was assessed by immunohistochemistry in peritumoral liver hepatocytes from 106 hepatitis B virus- (HBV-) related HCC patients who had undergone curative hepatectomy. The peritumoral EpCAM-positive group had a significantly worse overall survival (OS) () and recurrence-free survival (RFS) () compared to the negative group. Peritumoral CD13-positive patients were also associated with poor OS (), while not significantly associated with RFS. The adjusted multivariate COX proportional hazard regression analysis suggested that only the positive expression of peritumoral EpCAM precisely predicted poor OS. Being peritumoral EpCAM positive was also significantly associated with a larger tumor size, liver cirrhosis, and more frequent vascular invasion; however, no statistically significant association was observed between CD13 and any clinicopathological features. Taken together, peritumoral EpCAM and CD13 expression was associated with a poor prognosis, but EpCAM may be a better prognostic marker than CD13 in HBV-related HCC patients. In the future, peritumoral EpCAM could be a good target for adjuvant therapy after curative hepatectomy. 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. Phosphorylation of Histone H2A.X in Peripheral Blood Mononuclear Cells May Be a Useful Marker for Monitoring Cardiometabolic Risk in Nondiabetic Individuals Tue, 09 May 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/2050194/ Phosphorylation of H2A.X (serine 139) in the histone H2A family located in the downstream of the DNA damage kinase signaling cascade is an important indicator of DNA damage. Recently, phosphorylation of H2A.X was proposed as a sensitive biomarker of aging. This study investigated if phosphorylation of H2A.X in peripheral blood mononuclear cells (PBMCs) is associated with cardiometabolic risk in nondiabetic individuals. Basic parameters and oxidative stress/inflammatory markers were measured in nondiabetic healthy Koreans (). Phosphorylation of H2A.X was measured randomly among the study subjects using a flow cytometer. According to the number of metabolic syndrome risk factor (MetS-RF), the study subjects were subdivided into “super healthy” (, ) and “MetS-risk” (, ) groups. Phosphorylation of H2A.X in PBMCs (percentages and mean fluorescence intensity) was significantly higher in the MetS-risk group than in the super healthy group after adjusting for age, sex, cigarette smoking, and alcohol consumption. Phosphorylated H2A.X was positively correlated with the number of MetS-RF as well as waist circumference, blood pressures, triglyceride, HbA1C, oxidized LDL, high sensitivity C-reactive protein, tumor necrosis factor-alpha, and alanine aminotransferase after the adjustment. The present study suggested that phosphorylated H2A.X in circulating PBMCs measured by flow cytometer may be a useful marker for monitoring cardiometabolic risk in nondiabetic individuals. So Ra Yoon, Juhyun Song, Jong Hwa Lee, and Oh Yoen Kim Copyright © 2017 So Ra Yoon et al. All rights reserved. Serum Soluble ST2 and Diastolic Dysfunction in Hypertensive Patients Mon, 08 May 2017 10:30:19 +0000 http://www.hindawi.com/journals/dm/2017/2714095/ Background. Echocardiographic evaluation of left ventricular (LV) structural and functional alterations in hypertension has some limitations, potentially overcome by using biomarkers. ST2, a prognostic biomarker for heart failure and myocardial infarction patients, was less studied in hypertension. Aim. To analyze the relationship between serum ST2 levels and diastolic dysfunction (DD) in hypertension. Method. We enrolled 88 hypertensive outpatients (average age 65 years, 69.3% females) in a prospective study, stratified for presence of LV hypertrophy (LVH). For each patient clinical examination, lab workup (routine and serum ST2 levels) and echocardiography were performed. Results. Hypertensive patients with LVH had higher age, pulse pressure, mean arterial pressure, and serum ST2, while having lower serum albumin than those without LVH. Serum ST2 levels correlate with parameters of LV remodeling and DD. We found that 5.3% of ST2 level variability was caused by a 1-unit variation of cardiovascular risk. We identified cut-off values for discriminating hypertension with LVH versus that without LVH and grade 2 DD versus normal diastolic performance. Conclusion. ST2 could be used as diagnostic biomarker for cardiac remodeling and altered diastolic performance in hypertension, providing additional data to echocardiography. It could represent a milestone in early detection of cardiac performance alteration. Anca Daniela Farcaş, Florin Petru Anton, Cerasela Mihaela Goidescu, Iulia Laura Gavrilă, Luminiţa Animarie Vida-Simiti, and Mirela Anca Stoia Copyright © 2017 Anca Daniela Farcaş et al. All rights reserved. An Elevated Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis and Clinicopathological Characteristics in Patients with Colorectal Cancer: A Meta-Analysis Wed, 26 Apr 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/1053125/ Background. The aims of this study were to evaluate the clinicopathological and prognostic values of platelet-to-lymphocyte ratio (PLR) in colorectal cancer (CRC). Methods. The PubMed and Embase databases and the references of relevant studies were systematically searched. This study was performed with hazard ratios (HRs) and odd ratios (ORs) with corresponding 95% confidence intervals (CIs) as effect measures. Results. Our results indicated that elevated PLR was associated with poor overall survival (HR = 1.46, 95% CI = 1.23–1.73), disease-free survival (HR = 1.64, 95% CI = 1.17–2.30), cancer-specific survival (HR = 1.30, 95% CI = 1.12–1.51), and recurrence-free survival (HR = 1.38, 95% CI = 1.09–1.74) in CRC. For the clinicopathological characteristics, our results indicated that there were differences in the rate of elevated PLR between stages III/IV and I/II groups (OR = 1.38, 95% CI = 1.01–1.88), pT3/T4 and pT1/T2 groups (OR = 1.82, 95% CI = 1.03–3.20), and poor differentiation and moderate/well differentiation (OR = 2.59, 95% CI = 1.38–4.84). Conclusions. Our results indicated that elevated PLR predicted poor prognosis and clinicopathological characteristics in CRC and PLR is a convenient and low-cost blood-derived prognostic marker for CRC. Xuan-zhang Huang, Wen-jun Chen, Xi Zhang, Cong-cong Wu, Chao-ying Zhang, Shuang-shuang Sun, and Jian Wu Copyright © 2017 Xuan-zhang Huang et al. All rights reserved. Association of PECAM-1 Gene Polymorphisms with Kawasaki Disease in Chinese Children Sun, 23 Apr 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/2960502/ Kawasaki disease (KD) is an acute systemic vasculitis complicated by development of coronary artery lesions. PECAM-1 is a kind of cell adhesion molecule, which plays an important role in coronary artery disease. The relationship between PECAM-1 gene polymorphisms and their susceptibility to Kawasaki diseases (KD) is still unclear. In our study, we examined the PECAM-1 gene polymorphisms in 44 KD patients and 59 healthy children and revealed the correlation of PECAM-1 gene polymorphisms in KD children with and without coronary artery lesions (CAL). Zhuoying Li, Dong Han, Jie Jiang, Jia Chen, Lang Tian, and Zuocheng Yang Copyright © 2017 Zhuoying Li et al. All rights reserved. miR-135b Plays a Neuroprotective Role by Targeting GSK3β in MPP+-Intoxicated SH-SY5Y Cells Tue, 18 Apr 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/5806146/ miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson’s disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3β (GSK3β) was upregulated at mRNA and protein levels in MPP+-intoxicated SH-SY5Y cells in a dose- and time-dependent manner. MTT, TUNEL, and ELISA assays revealed that miR-135b overexpression significantly promoted cell proliferation and inhibited apoptosis and production of TNF-α and IL-1β in SH-SY5Y cells in the presence of MPP+. Luciferase reporter assay demonstrated that GSK3β was a direct target of miR-135b. Moreover, sodium nitroprusside (SNP), a GSK3β activator, dramatically reversed the effects of miR-135b upregulation on cell proliferation, apoptosis, and inflammatory cytokine production in MPP+-intoxicated SH-SY5Y cells. Taken together, miR-135b exerts a protective role via promotion of proliferation and suppression of apoptosis and neuroinflammation by targeting GSK3β in MPP+-intoxicated SH-SY5Y cells, providing a potential therapeutic target for the treatment of PD. Jianlei Zhang, Wei Liu, Yabo Wang, Shengnan Zhao, and Na Chang Copyright © 2017 Jianlei Zhang et al. All rights reserved. Potential Hepatoprotective Role of Galectin-3 during HCV Infection in End-Stage Renal Disease Patients Tue, 11 Apr 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/6275987/ Hepatitis C virus infection (HCV), one of the greatest causes of liver disease, is a frequent complication in patients with end-stage renal disease (ESRD) on dialysis. ESRD is defined as decreased glomerular filtration and also accompanied by impaired function of the immune system. Galectin-3 is a β-galactoside-binding lectin, involved in various biological processes including pathogenesis of chronic renal disease. The aim of our study was to estimate disease severity in ESRD HCV+ patients and analyze the serum concentrations of IL-1β, IL-4, IL-23, and IL-6; anti-HCV antibodies; and galectin-3. Also, we attempted to determine potential correlation between galectin-3 level and parameters of disease severity ALT and AST. Our results showed decreased levels of ALT and AST (), demonstrating less liver destruction in ESRD HCV+ patients in comparison to HCV+ patients. Increased levels of IL-6 () implicate a hepatoprotective role of IL-6 in these patients. Also, level of galectin-3 () in the serum of ESRD HCV+ patients was higher than that of HCV+ patients. This alteration was accompanied with negative correlation between galectin-3 and AST and ALT, respectively (; ). The presence of increased systemic levels of IL-6 and Gal-3 in ESRD HCV+ patients may be an attempt to counteract or limit ongoing proinflammatory processes and to downregulate chronic inflammation, suggesting the new aspects of HCV infection in ESRD patients. Ruzica Lukic, Nevena Gajovic, Ivan Jovanovic, Milena Jurisevic, Zeljko Mijailovic, Veljko Maric, Biljana Popovska Jovicic, and Nebojsa Arsenijevic Copyright © 2017 Ruzica Lukic et al. All rights reserved. miR-195 Regulates Proliferation and Apoptosis through Inhibiting the mTOR/p70s6k Signaling Pathway by Targeting HMGA2 in Esophageal Carcinoma Cells Mon, 10 Apr 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/8317913/ miR-195 is related to tumorigenesis and frequently inhibits cell proliferation and promotes apoptosis in various cancers, including esophageal carcinoma (EC). The mTOR/p70s6k signaling pathway, which is the major target pathway for HMGA2, regulates the survival and cell proliferation of many tumors and is commonly active in EC. The relationships of miR-195, HMGA2, and the mTOR/p70s6k signaling pathway in EC, however, remain unknown. In the present study, we found that the miR-195 level was significantly downregulated in EC tissues, while the mRNA expressions of HMGA2 were significantly upregulated. Dual-luciferase reporter assay demonstrated that HMGA2 is a target of miR-195. MTT assay and flow cytometry revealed that miR-195 overexpression inhibited cell proliferation and induced apoptosis by targeting HMGA2. We also found that HMGA2 restored the inhibitory effect of miR-195 on phosphorylation of mTOR and p70S6K. Furthermore, rapamycin, a specific inhibitor of the mTOR/p70S6K signaling pathway, decreased the levels of Ki-67 and Bcl-2/Bax ratio, inhibited cell proliferation, and promoted apoptosis in EC cells. In conclusion, upregulation of miR-195 significantly suppressed cell growth and induced apoptosis of EC cells via suppressing the mTOR/p70s6k signaling pathway by targeting HMGA2. Yong Li, Dapeng Wu, Pei Wang, Xiaohui Li, and Gongning Shi Copyright © 2017 Yong Li et al. All rights reserved. Functional Analysis of the Coronary Heart Disease Risk Locus on Chromosome 21q22 Tue, 28 Mar 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/1096916/ Background. The coronary heart disease (CHD) risk locus on 21q22 (lead SNP rs9982601) lies within a “gene desert.” The aim of this study was to assess if this locus is associated with CHD risk factors and to identify the functional variant(s) and gene(s) involved. Methods. A phenome scan was performed with UCLEB Consortium data. Allele-specific protein binding was studied using electrophoretic mobility shift assays. Dual-reporter luciferase assays were used to assess the impact of genetic variation on expression. Expression quantitative trait analysis was performed with Advanced Study of Aortic Pathology (ASAP) and Genotype-Tissue Expression (GTEx) consortium data. Results. A suggestive association between QT interval and the locus was observed (). One variant at the locus, rs28451064, showed allele-specific protein binding and its minor allele showed 12% higher luciferase expression ( = 4.82 × 10−3) compared to the common allele. The minor allele of rs9982601 was associated with higher expression of the closest upstream genes (SLC5A3 1.30-fold increase = 3.98 × 10−5; MRPS6 1.15-fold increase = 9.60 × 10−4) in aortic intima media in ASAP. Both rs9982601 and rs28451064 showed a suggestive association with MRPS6 expression in relevant tissues in the GTEx data. Conclusions. A candidate functional variant, rs28451064, was identified. Future work should focus on identifying the pathway(s) involved. Katherine E. Beaney, Andrew J. P. Smith, Lasse Folkersen, Jutta Palmen, S. Goya Wannamethee, Barbara J. Jefferis, Peter Whincup, Tom R. Gaunt, Juan P. Casas, Yoav Ben-Shlomo, Jacqueline F. Price, Meena Kumari, Andrew Wong, Ken Ong, Rebecca Hardy, Diana Kuh, Nicholas Wareham, Mika Kivimaki, Per Eriksson, Steve E. Humphries, and UCLEB Consortium Copyright © 2017 Katherine E. Beaney et al. All rights reserved. Can Mitochondria DNA Provide a Novel Biomarker for Evaluating the Risk and Prognosis of Colorectal Cancer? Thu, 16 Mar 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/5189803/ Colorectal cancer (CRC) was one of the most frequent cancers worldwide. Accurate risk and prognosis evaluation could obtain better quality of life and longer survival time for the patients. Current research hotspot was focus on the gene biomarker to evaluate the risk and prognosis. Mitochondrion contains its own DNA and regulates self-replicating so that it can be as a candidate biomarker for evaluating the risk and prognosis of colorectal cancer. But there were already huge controversies on this issue. The review was to summarize current viewpoints of the controversial issues and described our understanding from the four aspects including mtDNA copy number, mitochondrial displacement loop, mtDNA variation, and mtDNA microsatellite instability, wishing the summary of the mtDNA in colorectal cancer could provide a meaningful reference or a valuable direction in the future studies. Han Shuwen, Yang Xi, and Pan Yuefen Copyright © 2017 Han Shuwen et al. All rights reserved. Efficacy of Nucleot(s)ide Analogs Therapy in Patients with Unresectable HBV-Related Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis Wed, 15 Mar 2017 09:57:02 +0000 http://www.hindawi.com/journals/dm/2017/7075935/ Aim. To determine whether nucleot(s)ide analogs therapy has survival benefit for patients with HBV-related HCC after unresectable treatment. Method. A systematic search was conducted through seven electronic databases including PubMed, OVID, EMBASE, Cochrane Databases, Elsevier, Wiley Online Library, and BMJ Best Practice. All studies comparing NA combined with unresectable treatment versus unresectable treatment alone were considered for inclusion. The primary outcome was the overall survival (OS) after unresectable treatment for patients with HBV-related HCC. The secondary outcome was the progression-free survival (PFS). Results were expressed as hazard ratio (HR) for survival with 95% confidence intervals. Results. We included six studies with 994 patients: 409 patients in nucleot(s)ide analogs therapy group and 585 patients without antiviral therapy in control group. There were significant improvements for the overall survival (HR = 0.57; 95% CI = 0.47–0.70; p < 0.001) and progression-free survival (HR = 0.84; 95% CI = 0.71–0.99; p = 0.034) in the NA-treated group compared with the control group. Funnel plot showed that there was no significant publication bias in these studies. When it comes to antiviral drugs and operation method, it also showed benefit in NA-treated group. At the same time, overall mortality as well as mortality secondary to liver failure in NA-treated group was obviously lesser. Sensitivity analyses confirmed the robustness of the results. Conclusions. Nucleot(s)ide analogs therapy after unresectable treatment has potential beneficial effects in terms of overall survival and progression-free survival. NA therapy should be considered in clinical practice. Lingling He, Xiaoli Liu, Yalin Zhao, Shuan Zhang, Yuyong Jiang, Xianbo Wang, and Zhiyun Yang Copyright © 2017 Lingling He et al. All rights reserved. Association between IL-4 and IL-4R Polymorphisms and Periodontitis: A Meta-Analysis Tue, 14 Mar 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/8021279/ Background. Previous studies have revealed that gene polymorphisms of inflammatory factors may influence the development or progression of periodontitis, a main cause of tooth loss in adults; however, due to limitations of individual studies, inconsistent findings were reported. Objective. To meta-analytically investigate the relationship between periodontitis and the Interleukin-4 (IL-4) and Interleukin-4 receptor (IL-4R) gene polymorphisms. Methods. Databases were searched for relevant case-control studies. After study selection based on the predefined selection criteria, methodological quality assessment and data extraction were conducted independently by two reviewers, before subsequent statistical analyses. Results. 37 studies involving 4,385 patients and 5,168 controls were included. All the studied IL-4 polymorphisms were not significantly associated with periodontitis, except the -33C/T (CT versus CC: OR = 0.50, 95% CI = 0.28–0.88) associated with reduced AgP susceptibility. Positive association was found between IL-4R Q551 polymorphism and periodontitis susceptibility in three genetic models (R versus Q: OR = 1.59, 95% CI = 1.14–2.22; QR versus QQ: OR = 1.84, 95% CI = 1.21–2.80; RR + QR versus QQ: OR = 1.82, 95% CI = 1.22–2.72). Conclusions. A positive association exists between the IL-4R Q551R polymorphism and occurrence of CP. The IL-4 -33 CT genotype is negatively associated with the occurrence of AgP. Xiao-Wei Jia, Ya-Di Yuan, Zhong-Xiong Yao, Chang-Jing Wu, Xiang Chen, Xue-Hong Chen, Ying-Mei Lin, Xiang-Yu Meng, Xian-Tao Zeng, and Jun Shao Copyright © 2017 Xiao-Wei Jia et al. All rights reserved. The Exploration of Peptide Biomarkers in Malignant Pleural Effusion of Lung Cancer Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Mon, 13 Mar 2017 06:47:41 +0000 http://www.hindawi.com/journals/dm/2017/3160426/ Background. Diagnoses of malignant pleural effusion (MPE) are a crucial problem in clinics. In our study, we compared the peptide profiles of MPE and tuberculosis pleural effusion (TPE) to investigate the value of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in diagnosis of MPE. Material and Methods. The 46 MPE and 32 TPE were randomly assigned to training set and validation set. Peptides were isolated by weak cation exchange magnetic beads and peaks in the range of 800–10000 Da were analyzed. Comparing the peptide profile between 30 MPE and 22 TPE samples in training set by ClinProTools software, we screened the specific biomarkers and established a MALDI-TOF-MS classification of MPE. Finally, the other 16 MPE and 10 TPE were included to verify the model. We additionally determined carcinoembryonic antigen (CEA) in MPE and TPE samples using electrochemiluminescent immunoassay method. Results. Five peptide peaks (917.37 Da, 4469.39 Da, 1466.5 Da, 4585.21 Da, and 3216.87 Da) were selected to separate MPE and TPE by MALDI-TOF-MS. The sensitivity, specificity, and accuracy of the classification were 93.75%, 100%, and 96.15%, respectively, after blinded test. The sensitivity of CEA was significantly lower than MALDI-TOF-MS classification (). Conclusions. The results indicate MALDI-TOF-MS is a potential method for diagnosing MPE. Jing Xu, Bin Xu, Chuanhao Tang, Xiaoyan Li, Haifeng Qin, Weixia Wang, Hong Wang, Zhongyuan Wang, Liangliang Li, Zhihua Li, Hongjun Gao, Kun He, and Xiaoqing Liu Copyright © 2017 Jing Xu et al. All rights reserved. Genotyping of IL-4 −590 (C>T) Gene in Iraqi Asthma Patients Sun, 12 Mar 2017 08:10:16 +0000 http://www.hindawi.com/journals/dm/2017/5806236/ This study is the first investigation in Iraq dealing with genotyping of IL-4 −590 (C>T) gene, especially in Iraqi patients with asthma. We studied forty-eight blood samples collected from patients with asthma and compared with age-matched 25 healthy individuals as controls. The polymorphism results of IL-4 −590 (C>T) gene by using amplification refractory mutation system (ARMS-PCR) showed the presence of C and T alleles and three genotypes (CC, CT, and TT). Interestingly the frequency of C allele and CC genotype was higher in patients with asthma in comparison with the same allele and genotype in control (P 1 × 10−6). This increase was associated with an increased risk factor of asthma (odds ratio [OR] 9.21; 95% confidence interval [CI] 3.58–23.71). Genotypes analysis by using Hardy-Weinberg distribution showed no significant differences between patients with asthma and healthy subjects. In conclusion, the increasing risk of asthma was associated with C allele and the CC genotype and these are revealed as etiological fraction with risk by having this disease, while the T allele percentage ratio in controls was higher when it is compared with asthma patients suggesting that these alleles have a protective effect (preventive fraction). Ihsan A. Hussein and Saddam H. Jaber Copyright © 2017 Ihsan A. Hussein and Saddam H. Jaber. All rights reserved. Corrigendum to “Predictive Value of Plasma MicroRNA-216a/b in the Diagnosis of Esophageal Squamous Cell Carcinoma” Sun, 12 Mar 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/3437679/ Shuling Dong, Huiqing Yin, Cuicui Dong, Kaiyan Sun, Pin Lv, Weiwei Meng, Liang Ming, and Fucheng He Copyright © 2017 Shuling Dong et al. All rights reserved. Association between VEGF Gene Polymorphisms and In-Stent Restenosis after Coronary Intervention Treated with Bare Metal Stent Tue, 07 Mar 2017 07:00:05 +0000 http://www.hindawi.com/journals/dm/2017/9548612/ Background. In-stent restenosis (ISR) is the gradual narrowing of the vessel lumen after coronary stent implantation due to the increase in vascular smooth muscle cell proliferation. Vascular endothelial growth factor (VEGF) protein plays an important role in this process. Our aim was to analyze the association of single nucleotide polymorphisms of the VEGF gene (rs2010963 and rs6999447) with the occurrence of ISR after coronary artery bare metal stent (BMS) implantation. Methods. 205 patients with a history of BMS implantation and a repeated coronarography were prospectively enrolled. Patients were assigned to diffuse restenosis group () and control group () and VEGF genotypes were determined. Results. Diffuse ISR was significantly more frequently observed in patients with homozygous normal genotype of rs2010963 polymorphism, and this polymorphism was independently associated with diffuse ISR. Conclusions. RS2010963 is associated with higher incidence of development of diffuse coronary ISR in patients treated with BMS implantation. Zsolt Bagyura, Loretta Kiss, Kristóf Hirschberg, Balázs Berta, Gábor Széplaki, Árpád Lux, Zsolt Szelid, Pál Soós, and Béla Merkely Copyright © 2017 Zsolt Bagyura et al. All rights reserved. Ischemia-Modified Albumin as a Marker of Acute Coronary Syndrome: The Case for Revising the Concept of “N-Terminal Modification” to “Fatty Acid Occupation” of Albumin Sun, 05 Mar 2017 10:02:18 +0000 http://www.hindawi.com/journals/dm/2017/5692583/ Ischemia-modified albumin (IMA) is assumed “N-terminal modified” albumin which is generated immediately following myocardial ischemia. The diagnosis of IMA is based on reduced cobalt binding affinity to albumin which is attributed mainly to incapability of cobalt to bind at albumin’s modified N-terminus. Although the albumin cobalt binding test was accepted as a potentially powerful marker for discriminating acute coronary syndrome from nonischemic chest pain, its usefulness has been brought into question in recent years. Patients with acutely ischemic myocardium exhibit a rapid increase in serum levels of fatty acids (FAs). Almost all released FAs are strongly bound to albumin which create conformational changes in the protein with resultant reduced cobalt binding affinity. There is a clear metabolic and temporal relationship between IMA measured via albumin cobalt binding testing and serum levels of FAs. In line with what has been suggested recently in the literature, we conclude that a shift from the concept of “N-terminal modified” to “FA-occupied” albumin is required, as this better describes IMA in patients with acute coronary syndrome. We also offer “oxidation modified albumin, OMA,” which is conceptually different from the “FA-occupied” IMA, to describe modification of albumin in chronic disease associated with increased oxidative stress. Ismail Oran and Bulent Oran Copyright © 2017 Ismail Oran and Bulent Oran. All rights reserved. A Panel of CA19-9, Ca125, and Ca15-3 as the Enhanced Test for the Differential Diagnosis of the Pancreatic Lesion Sun, 05 Mar 2017 07:14:08 +0000 http://www.hindawi.com/journals/dm/2017/8629712/ Background. Proper diagnosis of pancreatic lesion etiology is a challenging clinical dilemma. Studies suggest that surgery for suspected pancreatic ductal adenocarcinoma (PDAC) reveals a benign lesion in 5% to 13% of cases. The aim of our study was to assess whether routinely used biomarkers such as CA19-9, Ca125, Ca15-3, and CEA, when combined, can potentially yield an accurate test predicting pancreatic lesion etiology. Methods. We retrospectively analyzed data of 326 patients who underwent a diagnostic process due to pancreatic lesions of unknown etiology. Results. We found statistically significant differences in mean levels of all biomarkers. In logistic regression model, we applied levels CA19-9, Ca125, and Ca15-3 as variables. Two validation methods were used, namely, random data split into training and validation groups and bootstrapping. Afterward, we built ROC curve using the model that we had created, reaching AUC = 0,801. With an optimal cut-off point, it achieved specificity of 81,2% and sensitivity of 63,10%. Our proposed model has superior diagnostic accuracy to both CA19-9 ( = 0,0194) and CA125 ( = 0,0026). Conclusion. We propose a test that is superior to CA19-9 in a differential diagnosis of pancreatic lesion etiology. Although our test fails to reach exceptionally high accuracy, its feasibility and cost-effectiveness make it clinically useful. Piotr Hogendorf, Aleksander Skulimowski, Adam Durczyński, Anna Kumor, Grażyna Poznańska, Aleksandra Oleśna, Joanna Rut, and Janusz Strzelczyk Copyright © 2017 Piotr Hogendorf et al. All rights reserved. Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases Wed, 01 Mar 2017 07:44:21 +0000 http://www.hindawi.com/journals/dm/2017/5756102/ High-mobility group box 1 (HMGB1) functions as a proinflammatory cytokine and is one of the most intriguing molecules in inflammatory disorders and cancers. Notably, HMGB1 is a potential therapeutic target and novel biomarker in related diseases. However, the diagnostic value of HMGB1 for benign and malignant asbestos-related diseases (ARDs) remains unclear. In this work, we detected preoperative serum HMGB1 levels in Chinese asbestos-exposed (AE) and ARDs populations and further evaluated the diagnostic value of HMGB1 in patients with certain types of ARDs, including those with pleural plaques, asbestosis, or malignant mesothelioma (MM). The experimental data presented that the serum level of HMGB1 was significantly elevated in AE and ARDs subjects. Our findings indicated that serum HMGB1 is a sensitive and specific biomarker for discriminating asbestosis- and MM-affected individuals from healthy or AE individuals. In addition, serum matrix metalloproteinases 2 and 9 are not correlated with HMGB1 in ARDs. Thus, our study provides supporting evidence for HMGB1 as a potential biomarker either for the clinical diagnosis of high-risk AE cohorts or for evaluating ARDs. Shibo Ying, Zhaoqiang Jiang, Xianglei He, Min Yu, Riping Chen, Junqiang Chen, Guoqing Ru, Yuan Chen, Wanyuan Chen, Lijin Zhu, Tao Li, Yixiao Zhang, Xinnian Guo, Xianhong Yin, Xing Zhang, and Jianlin Lou Copyright © 2017 Shibo Ying et al. All rights reserved. Hyperferritinemia as a Diagnostic Marker for Severe Fever with Thrombocytopenia Syndrome Tue, 28 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/6727184/ Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease in East Asia with high mortality. Few studies have examined markers that suggest SFTS in febrile patients. To determine useful biochemical markers for SFTS, patients aged 18 years or older with SFTS or microbiologically confirmed community-onset bacteremia with thrombocytopenia (BT) at presentation between June 2013 and December 2015 were included from two tertiary university hospitals in Republic of Korea retrospectively. Eleven patients with SFTS and 62 patients with bacteremia and thrombocytopenia were identified in the study period. Age and sex did not show significant difference among two groups. Fever was more commonly observed but comorbidities were less common in SFTS than in BT (, each). The areas under the curves of serum ferritin, C-reactive protein, white blood cell count, serum procalcitonin, and fibrinogen were above 0.9, indicating the discriminative power of these biomarkers (1.000, 0.991, 0.963, 0.931, and 0.934, resp., all ). The optimal cutoff value of serum ferritin was 3,822 ng/mL in this study. These results suggest that hyperferritinemia is a typical laboratory feature of SFTS, and the serum ferritin level can be used as a marker for clinicians suspecting SFTS. Uh Jin Kim, Tae hoon Oh, Bansuk Kim, Seong Eun Kim, Seung-Ji Kang, Kyung-Hwa Park, Sook-In Jung, and Hee-Chang Jang Copyright © 2017 Uh Jin Kim et al. All rights reserved. A Novel Panel of Serum Biomarkers for MPM Diagnosis Tue, 28 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/dm/2017/3510984/ Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM), a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin). The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type. All the new markers found differentially expressed in MPM and healthy subjects, by proteomic and genomic approaches, have been validated in the serum by the use of specific ELISA. The combined approach, using tools of genomics and proteomics, is found to be highly innovative for this type of disease and led to the identification of new serum markers in the diagnosis of MPM. These results, if confirmed in a larger series, may have a strong impact in this area, because early detection of this cancer in people at high risk could significantly improve the course of the disease and the clinical approach to an individualized therapy. A. Bonotti, R. Foddis, S. Landi, O. Melaiu, C. De Santi, L. Giusti, E. Donadio, F. Ciregia, M. R. Mazzoni, A. Lucacchini, M. Bovenzi, M. Comar, E. Pantani, A. Pistelli, and A. Cristaudo Copyright © 2017 A. Bonotti et al. All rights reserved. Combined Genetic Biomarkers Confer Susceptibility to Risk of Urothelial Bladder Carcinoma in a Saudi Population Mon, 27 Feb 2017 07:06:04 +0000 http://www.hindawi.com/journals/dm/2017/1474560/ We evaluated the associations between seven single nucleotide polymorphisms and susceptibility to urothelial bladder carcinoma (UBC) in a Saudi population. Genomic DNA was taken from buccal cells of 52 patients with UBC and 104 controls for genotyping of GSTT1, GSTM1, rs4646903, rs1048943, TP53 rs1042522, rs1801133, and rs1801394 using PCR and TaqMan® assays. The rs1801133 and rs1801394 variants showed strong associations with UBC (OR = 2.3, ; OR = 2.6, , resp.). Homozygosity of Pro72 conferred a significant double risk in cases compared with controls (30.8% versus 15.4%), but the homozygote Arg/Arg had no effect on risk. Genotypic combinations of GSTM1/GSTT1, rs4646903/rs1048943, and rs1801133/rs1801394 exhibited significant linkage with the disease (, ; , ; and , , resp.). The GSTM1 and rs1042522Arg and rs1801394G variant alleles were more frequent in current smokers with UBC (52.4%, 52.5%, and 64.3%, resp.) than were the corresponding wild-types. Despite some variants having only a slight effect on UBC risk, the interaction effect of combined genetic biomarkers—or even the presence of one copy of a variant allele—is potentially much greater. Perhaps more studies regarding next-generation genetic sequencing and its utility can add to the risk of UBC. Nasser Attia Elhawary, Anmar Nassir, Hesham Saada, Anas Dannoun, Omar Qoqandi, Ammar Alsharif, and Mohammed Taher Tayeb Copyright © 2017 Nasser Attia Elhawary et al. All rights reserved.