Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Circulating Omentin-1 Levels Are Decreased in Dilated Cardiomyopathy Patients with Overt Heart Failure Tue, 24 May 2016 08:41:02 +0000 http://www.hindawi.com/journals/dm/2016/6762825/ Background. Recent evidence demonstrated that the circulating levels of omentin-1 are related to the presence of ischemic heart disease and heart failure. However, omentin-1 plasma levels in patients with nonischemic dilated cardiomyopathy (DCM), which is the most common etiology of heart failure, have yet to be investigated. Methods. Plasma levels of omentin-1 and adiponectin were measured in 100 patients with DCM and 45 healthy controls. Results. Plasma omentin-1 levels significantly decreased in DCM patients compared with the control group, whereas adiponectin levels significantly increased in DCM patients compared with the control group. Plasma omentin-1 levels were negatively correlated with adiponectin (, ), C-reactive protein (CRP) (, ), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (, ) levels as well as left ventricular end-diastolic diameter (LVEDD) (, ) but were positively correlated with left ventricular ejection fraction (LVEF) (, ). Plasma adiponectin levels were positively correlated with CRP (, ) and NT-proBNP (, ) levels but were negatively correlated with fasting glucose (, ) and LVEF (, ) levels. Furthermore, omentin-1 (OR 0.983, 95% CI 0.970 to 0.996; ) levels were independently associated with the presence of DCM before NT-proBNP was added. Conclusions. Omentin-1 is a novel biomarker of DCM. Ying Huang, Yingzhong Lin, Shumin Zhang, Zhijian Wang, Jianwei Zhang, Chao Chang, Ling Liu, Qingwei Ji, and Xiaofei Liu Copyright © 2016 Ying Huang et al. All rights reserved. Immunohistochemical Expression of VEGF and Podoplanin in Uterine Cervical Squamous Intraepithelial Lesions Tue, 24 May 2016 05:51:16 +0000 http://www.hindawi.com/journals/dm/2016/8293196/ VEGF and podoplanin (PDPN) have been identified as angiogenesis and/or lymphangiogenesis regulators and might be essential to restrict tumor growth, progression, and metastasis. In the present study, we evaluate the association between the expression of these markers and CIN grade. Immunohistochemistry was performed in 234 uterine cervical samples using conventional histologic sections or TMA with the monoclonal antibodies to VEGF (C-1 clone) and podoplanin (D2-40 clone). Positive-staining rates of VEGF in 191 CIN specimens were significantly associated with histological grade (). Negative and/or focal immunostaining for PDPN were more frequent in CIN 3 (). We found that patients with CIN 3 more frequently had strong and more diffuse staining for VEGF and diminished staining for PDPN (). Strong and more diffuse VEGF immunoexpressions in CIN 2 and CIN 3 were detected when compared to CIN 1. Negative and/or focal PDPN immunoexpression appear to be more frequent in CIN 3. Moderate to strong VEGF expression may be a tendency among patients with high-grade lesions and diminished PDPN expression. Patrícia Napoli Belfort-Mattos, Gustavo Rubino de Azevedo Focchi, Julisa Chamorro Lascasas Ribalta, Tatiana Megale De Lima, Carmen Regina Nogueira Carvalho, Fernanda Kesselring Tso, and Neila Maria De Góis Speck Copyright © 2016 Patrícia Napoli Belfort-Mattos et al. All rights reserved. Plasma miR-10a: A Potential Biomarker for Coronary Artery Disease Sun, 22 May 2016 11:11:00 +0000 http://www.hindawi.com/journals/dm/2016/3841927/ Aims. MicroRNAs (miRNAs) are involved in the pathogenesis of coronary artery disease (CAD). The objective of this study is to determine plasma levels of miR-10a in CAD and analyze its association with the severity of CAD. Materials and Methods. Plasma miR-10a levels in 60 CAD patients including stable angina pectoris (SAP) (), unstable angina pectoris (UAP) or non-ST elevation myocardial infarction (MI) (NSTEMI) (), or ST elevation MI (STEMI) () and 20 non-CAD subjects were assessed by real-time polymerase chain reaction (qRT-PCR), and associations of miR-10a levels with risk factors of CAD and its severity were analyzed. Results. The qRT-PCR results showed that plasma miR-10a levels were decreased in CAD patients, and CAD with high SYNTAX scores or STEMI was significantly associated with lower miR-10a levels. Conclusions. Lower plasma miR-10a levels were negatively associated with the presence as well as severity of CAD, and plasma miR-10a can act as a potential biomarker for estimating the presence and severity of CAD. Liyun Luo, Bairong Chen, Songbiao Li, Xiaoliang Wei, Tianmin Liu, Yin Huang, and Xiufang Lin Copyright © 2016 Liyun Luo et al. All rights reserved. Comparative Study of Circulating MMP-7, CCL18, KL-6, SP-A, and SP-D as Disease Markers of Idiopathic Pulmonary Fibrosis Tue, 17 May 2016 14:22:14 +0000 http://www.hindawi.com/journals/dm/2016/4759040/ Background. Recent reports indicate that matrix metalloproteinase-7 (MMP-7) and CC-chemokine ligand 18 (CCL18) are potential disease markers of idiopathic pulmonary fibrosis (IPF). The objective of this study was to perform direct comparisons of these two biomarkers with three well-investigated serum markers of IPF, Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), and SP-D. Methods. The serum levels of MMP-7, CCL18, KL-6, SP-A, and SP-D were evaluated in 65 patients with IPF, 31 patients with bacterial pneumonia, and 101 healthy controls. The prognostic performance of these five biomarkers was evaluated in patients with IPF. Results. The serum levels of MMP-7, KL-6, and SP-D in patients with IPF were significantly elevated compared to those in patients with bacterial pneumonia and in the healthy controls. Multivariate survival analysis showed that serum MMP-7 and KL-6 levels were independent predictors in IPF patients. Moreover, elevated levels of both KL-6 and MMP-7 were associated with poorer survival rates in IPF patients, and the combination of both markers provided the best risk discrimination using the C statistic. Conclusions. The present results indicated that MMP-7 and KL-6 were promising prognostic markers of IPF, and the combination of the two markers might improve survival prediction in patients with IPF. Kosuke Hamai, Hiroshi Iwamoto, Nobuhisa Ishikawa, Yasushi Horimasu, Takeshi Masuda, Shintaro Miyamoto, Taku Nakashima, Shinichiro Ohshimo, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori, and Nobuoki Kohno Copyright © 2016 Kosuke Hamai et al. All rights reserved. Evaluation of Adipokines, Inflammatory Markers, and Sex Hormones in Simple and Complex Breast Cysts’ Fluid Thu, 12 May 2016 17:23:50 +0000 http://www.hindawi.com/journals/dm/2016/5174929/ Objective. The aim of the study was to analyze the association between levels of adipokines in the breast cyst fluid and in the circulation in relation to the type of cysts. Material and Measurements. A cross-sectional study involved 86 women with breast cysts (42 with simple cysts and 44 with complex cysts). Plasma and breast cyst fluid leptin, adiponectin, visfatin/NAMPT, resistin, TNF-α, and IL-6 levels, in addition to serum levels of estradiol, progesterone and prolactin, and anthropometric parameters and body composition (by bioimpedance method), were measured. Results. The levels of leptin, adiponectin, and resistin were significantly lower in breast cyst fluid than in plasma regardless of the cyst type. Contrarily, the levels of visfatin/NAMPT and TNF-α were significantly increased, and IL-6 levels were similar in the breast cyst fluid and plasma in both study groups. There was no correlation between corresponding levels of leptin, adiponectin, resistin, visfatin/NAMPT, TNF-α, and IL-6 in breast cyst fluid and plasma. Conclusions. Higher levels of visfatin/NAMPT and TNF-α in the fluid from simple and complex breast cysts than in plasma suggest that their local production is related to inflammation. Paweł Madej, Grzegorz Franik, Piotr Kurpas, Aleksander Owczarek, Jerzy Chudek, and Magdalena Olszanecka-Glinianowicz Copyright © 2016 Paweł Madej et al. All rights reserved. Influence of βS-Globin Haplotypes and Hydroxyurea on Arginase I Levels in Sickle Cell Disease Wed, 04 May 2016 10:59:47 +0000 http://www.hindawi.com/journals/dm/2016/9172726/ Introduction. Sickle cell disease (SCD) is characterized by hemoglobin S homozygosity, leading to hemolysis and vasoocclusion. The hemolysis releases arginase I, an enzyme that decreases the bioavailability of nitric oxide, worsening the symptoms. The different SCD haplotypes are related to clinical symptoms and varied hemoglobin F (HbF) concentration. The aim of this study was to evaluate the impact of the βS gene haplotypes and HbF concentration on arginase I levels in SCD patients. Methods. Fifty SCD adult patients were enrolled in the study and 20 blood donors composed the control group. Arginase I was measured by ELISA. The βS haplotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses were performed with GraphPad Prism program and the significance level was . Results. Significant increase was observed in the arginase I levels in SCD patients compared to the control group (). The comparison between the levels of arginase I in three haplotypes groups showed a difference between the Bantu/Bantu Bantu/Benin groups; Bantu/Bantu Benin/Benin, independent of HU dosage. An inverse correlation with the arginase I levels and HbF concentration was observed. Conclusion. The results support the hypothesis that arginase I is associated with HbF concentration, also measured indirectly by the association with haplotypes. J. A. Moreira, R. P. G. Machado, M. R. Laurentino, Romelia Pinheiro Gonçalves Lemes, M. C. Barbosa, T. E. Santos, I. C. J. Bandeira, and A. M. C. Martins Copyright © 2016 J. A. Moreira et al. All rights reserved. The Relationship between Betatrophin Levels in Blood and T2DM: A Systematic Review and Meta-Analysis Tue, 03 May 2016 12:40:01 +0000 http://www.hindawi.com/journals/dm/2016/9391837/ Background. In order to clarify previous ambiguous research conclusions, a meta-analysis was made to investigate the relationship between betatrophin levels in blood and type 2 diabetes mellitus (T2DM). Methods. We have searched all the English and Chinese references regarding the relationship between betatrophin and diabetes in database both manually and online. Strict criteria have been established to include and exclude articles, with Mean and Standard Deviation as statistics to evaluate strength of association. We have chosen either fixed- or random effect model according to heterogeneity inspection results and used Begg’s test and Egger’s test to analyze publication bias. Results. A total of 11 studies were included in this meta-analysis. Meta-analysis indicated a significant association between betatrophin and T2DM (Mean: 329.46; 95% confidence interval: 182.51 to 476.42, ). However, in the subgroup analysis, there was no significant statistic between betatrophin concentration and T2DM within Caucasian population (Mean: 98.40; 95% confidence interval: −1585.08 to 1781.88, ). Conclusions. Such relationship may suggest preference for association between betatrophin and T2DM in different population. Song Yue, Jingyang Wu, Jiahua Zhang, Lei Liu, and Lei Chen Copyright © 2016 Song Yue et al. All rights reserved. CYC1 Predicts Poor Prognosis in Patients with Breast Cancer Thu, 28 Apr 2016 08:50:20 +0000 http://www.hindawi.com/journals/dm/2016/3528064/ Cytochrome c-1 (CYC1) is an important subunit of mitochondrial complex III. However, its role in tumor progression is unclear. We found that CYC1 was upregulated in breast tumor tissues, especially in tissues with lymph node metastasis. And higher expression of CYC1 correlates with poor prognosis in breast cancer patients using online databases and tools. Then we confirmed that CYC1 contributed to metastasis and proliferation in two highly metastatic human breast cancer cell lines. Digging into the biological function of CYC1, we found the activity of mitochondrial complex III decreased due to silencing CYC1. Then the ratio of AMP to ATP increased and AMPK was activated. Analyzing units of other mitochondrial complexes, we did not find knockdown of CYC1 expression reduced expression of any other unit of OXPHOS. We concluded that CYC1 promoted tumor metastasis via suppressing activation of AMPK and contributed to tumor growth via facilitating production of ATP. Our results indicated that CYC1 plays crucial roles in breast cancer progression and might be a predictive factor assisting future patient diagnosis. Yingyan Han, Shujuan Sun, Meisong Zhao, Zeyu Zhang, Song Gong, Peipei Gao, Jia Liu, Jianfeng Zhou, Ding Ma, Qinglei Gao, and Peng Wu Copyright © 2016 Yingyan Han et al. All rights reserved. TP53 Mutations and Survival in Osteosarcoma Patients: A Meta-Analysis of Published Data Wed, 27 Apr 2016 11:26:12 +0000 http://www.hindawi.com/journals/dm/2016/4639575/ Several research groups have examined the association between TP53 mutations and prognosis in human osteosarcoma. However, the results were controversial. The purpose of this study was to evaluate the prognostic value of TP53 mutations in osteosarcoma patients. A meta-analysis was conducted with all eligible studies which quantitatively evaluated the relationship between TP53 mutations and clinical outcome of osteosarcoma patients. Eight studies with a total of 210 patients with osteosarcoma were included in this meta-analysis. The risk ratio (RR) with a 95% confidence interval (95% CI) was calculated to assess the effect of TP53 mutations on 2-year overall survival. The quantitative synthesis of 8 published studies showed that TP53 mutations were associated with 2-year overall survival in osteosarcoma patients. These data suggested that TP53 mutations had an unfavorable impact on 2-year overall survival when compared to the counterparts with wild type (WT) TP53 (RR: 1.79; 95% CI: 1.12 to 2.84; ; %). There was no between-study heterogeneity. TP53 mutations are an effective prognostic marker for survival of patients with osteosarcoma. However, further large-scale prospective trials should be performed to clarify the prognostic value of TP53 mutations on 3- or 5-year survival in osteosarcoma patients. Zhe Chen, Jiayi Guo, Kun Zhang, and Yanxing Guo Copyright © 2016 Zhe Chen et al. All rights reserved. Detection of Autoantibodies to Vascular Endothelial Growth Factor Receptor-3 in Bile Duct Ligated Rats and Correlations with a Panel of Traditional Markers of Liver Diseases Sun, 24 Apr 2016 15:38:34 +0000 http://www.hindawi.com/journals/dm/2016/6597970/ There is a need for new noninvasive biomarkers (NIBMs) able to assess cholestasis and fibrosis in chronic cholestatic liver diseases (CCLDs). Tumorigenesis can arise from CCLDs. Therefore, autoantibodies to tumor-associated antigens (TAA) may be early produced in response to abnormal self-antigen expression caused by cholestatic injury. Vascular endothelial growth factor receptor-3 (VEGFR-3) has TAA potential since it is involved in cholangiocytes and lymphatic vessels proliferations during CCLDs. This study aims to detect autoantibodies directed at VEGFR-3 during bile duct ligation- (BDL-) induced cholestatic injury in rat sera and investigate whether they could be associated with traditional markers of liver damage, cholestasis, and fibrosis. An ELISA was performed to detect anti-VEGFR-3 autoantibodies in sera of rats with different degree of liver injury and results were correlated with aminotransferases, total bilirubin, and the relative fibrotic area. Mean absorbances of anti-VEGFR-3 autoantibodies were significantly increased from week one to week five after BDL. The highest correlation was observed with total bilirubin ( = 0.8450, ). In conclusion, anti-VEGFR-3 autoantibodies are early produced during BDL-induced cholestatic injury, and they are closely related to cholestasis, suggesting the potential of anti-VEGFR-3 autoantibodies as NIBMs of cholestasis in CCLDs and justifying the need for further investigations in patients with CCLD. Florent Duval, Delia Elva Cruz-Vega, Ivonne González-Gamboa, María Teresa González-Garza, Fernando Ponz, Flora Sánchez, Gabriela Alarcón-Galván, and Jorge E. Moreno-Cuevas Copyright © 2016 Florent Duval et al. All rights reserved. IL-4 Gene Polymorphism May Contribute to an Increased Risk of Atopic Dermatitis in Children Sun, 24 Apr 2016 12:23:35 +0000 http://www.hindawi.com/journals/dm/2016/1021942/ This study aimed to elucidate the associations between interleukin-4 (IL-4) single nucleotide polymorphisms (SNPs), 590C/T and 589C/T, serum IL-4 levels, and atopic dermatitis (AD) in children. Methods. A total of 82 children with AD were randomly selected as the case group and divided into mild group (15 cases), moderate group (46 cases), and severe group (21 cases). Additionally, 100 healthy children were selected as the control group. Genotype frequencies of IL-4 SNPs were detected by PCR-RFLP. Serum IL-4 levels were measured by ELISA. Results. Significant differences were shown in genotype distributions and allele frequencies of 589C/T and allele frequencies of 590C/T (all ). Serum IL-4 levels in the mild, moderate, and severe groups were significantly higher than those in the control group; significant differences were found among these three groups with increased severity of AD. Serum IL-4 levels of heterozygote and mutant homozygote carriers in the mild, moderate, and severe groups were higher than wild homozygote carriers in those three groups and the control group (all ). Conclusion. 590T and 589T alleles of IL-4 gene may be associated with high levels of serum IL-4, which may increase the risk of AD in children. Hong Shang, Xiu-Li Cao, Yu-Jie Wan, Jin Meng, and Lu-Hong Guo Copyright © 2016 Hong Shang et al. All rights reserved. Prognostic and Clinicopathological Significance of Downregulated p16 Expression in Patients with Bladder Cancer: A Systematic Review and Meta-Analysis Wed, 20 Apr 2016 12:58:25 +0000 http://www.hindawi.com/journals/dm/2016/5259602/ p16, encoded by the CDKN2A gene, is a tumor suppressor that has been widely studied in cancer research. However, the relationship of p16 with prognostic and clinicopathological parameters in patients with bladder cancer remains unclear. Data inclusion criteria were articles reporting on the relationship between p16 expression and the prognosis or clinicopathology in patients with bladder cancer. Meta-analyses were performed with Stata software. Hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated to evaluate the relative risks. The source of heterogeneity was analyzed by subgroup analysis. A total of 37 studies with 2246 cases were included and analyzed. The results identified an important link between downregulated p16 expression and poor prognosis in patients with bladder cancer in terms of recurrence-free survival (RFS), overall survival (OS), progression-free survival (PFS), and some clinicopathological parameters including clinical staging, pathological degree, and lymph node metastasis. Subgroup analysis also showed that low p16 expression could function as a warning sign for RFS and PFS in patients with early-stage (Ta–T1) bladder cancer. In conclusion, p16 might play an essential role in the deterioration of bladder cancer and could serve as a biomarker for the prediction for patients’ progression and prognosis. Xiaoning Gan, Xiaomiao Lin, Rongquan He, Xinggu Lin, Hanlin Wang, Liyan Yan, Hong Zhou, Hui Qin, and Gang Chen Copyright © 2016 Xiaoning Gan et al. All rights reserved. Association of Common Variants in MMPs with Periodontitis Risk Tue, 19 Apr 2016 07:14:22 +0000 http://www.hindawi.com/journals/dm/2016/1545974/ Background. Matrix metalloproteinases (MMPs) are considered to play an important role during tissue remodeling and extracellular matrix degradation. And functional polymorphisms in MMPs genes have been reported to be associated with the increased risk of periodontitis. Recently, many studies have investigated the association between MMPs polymorphisms and periodontitis risk. However, the results remain inconclusive. In order to quantify the influence of MMPs polymorphisms on the susceptibility to periodontitis, we performed a meta-analysis and systematic review. Results. Overall, this comprehensive meta-analysis included a total of 17 related studies, including 2399 cases and 2002 healthy control subjects. Our results revealed that although studies of the association between MMP-8 −799 C/T variant and the susceptibility to periodontitis have not yielded consistent results, MMP-1 (−1607 1G/2G, −519 A/G, and −422 A/T), MMP-2 (−1575 G/A, −1306 C/T, −790 T/G, and −735 C/T), MMP-3 (−1171 5A/6A), MMP-8 (−381 A/G and +17 C/G), MMP-9 (−1562 C/T and +279 R/Q), and MMP-12 (−357 Asn/Ser), as well as MMP-13 (−77 A/G, 11A/12A) SNPs are not related to periodontitis risk. Conclusions. No association of these common MMPs variants with the susceptibility to periodontitis was found; however, further larger-scale and multiethnic genetic studies on this topic are expected to be conducted to validate our results. Wenyang Li, Ying Zhu, Pradeep Singh, Deepal Haresh Ajmera, Jinlin Song, and Ping Ji Copyright © 2016 Wenyang Li et al. All rights reserved. The Diagnostic Value of the Pleural Fluid C-Reactive Protein in Parapneumonic Effusions Mon, 18 Apr 2016 13:04:07 +0000 http://www.hindawi.com/journals/dm/2016/7539780/ Purpose. The aim of this study was to evaluate the sensitivity of pleural C-reactive protein (CRP) biomarker levels in identifying parapneumonic effusions. Methods. A single-center, retrospective review of 244 patients diagnosed with pleural effusions was initiated among patients at the Rabin Medical Center, Petah Tikva, Israel, between January 2011 and December 2013. The patients were categorized into 4 groups according to their type of pleural effusion as follows: heart failure, malignant, post-lung transplantation, and parapneumonic effusion. Results. The pleural CRP levels significantly differentiated the four groups () with the following means: parapneumonic effusion,  mg/dL; lung transplant,  mg/dL; malignancy,  mg/dL; and heart failure,  mg/dL. The pleural fluid CRP cut-off value for differentiating among parapneumonic effusions and the other 3 groups was 1.38 mg/dL. The sensitivity, specificity, positive predictive value, and negative predictive value were 84.2%, 71.5%, 37%, and 95%, respectively. A backward logistic regression model selected CRP as the single predictor of parapneumonic effusion (OR = 1.59, 95% CI = 1.37–1.89). Conclusions. Pleural fluid CRP levels can be used to distinguish between parapneumonic effusions and other types of exudative effusions. CRP levels < 0.64 mg/dL are likely to indicate a pleural effusion from congestive heart failure, whereas levels ≥ 1.38 mg/dL are suggestive of an infectious etiology. Shimon Izhakian, Walter G. Wasser, Benjamin D. Fox, Baruch Vainshelboim, and Mordechai R. Kramer Copyright © 2016 Shimon Izhakian et al. All rights reserved. Postnatal Changes in Humerus Cortical Bone Thickness Reflect the Development of Metabolic Bone Disease in Preterm Infants Mon, 18 Apr 2016 13:03:57 +0000 http://www.hindawi.com/journals/dm/2016/2176594/ Objective. To use cortical bone thickness (CBT) of the humerus to identify risk factors for the development of metabolic bone disease in preterm infants. Methods. Twenty-seven infants born at <32 weeks of gestational age, with a birth weight of <1,500 g, were enrolled. Humeral CBT was measured from chest radiographs at birth and at 27-28, 31-32, and 36–44 weeks of postmenstrual age (PMA). The risk factors for the development of osteomalacia were statistically analyzed. Results. The humeral CBT at 36–44 weeks of PMA was positively correlated with gestational age and birth weight and negatively correlated with the duration of mechanical ventilation. CBT increased with PMA, except in six very early preterm infants in whom it decreased. Based on logistic regression analysis, gestational age and duration of mechanical ventilation were identified as risk factors for cortical bone thinning. Conclusions. Humeral CBT may serve as a radiologic marker of metabolic bone disease at 36–44 weeks of PMA in preterm infants. Cortical bones of extremely preterm infants are fragile, even when age is corrected for term, and require extreme care to lower the risk of fractures. Shuko Tokuriki, Aiko Igarashi, Takashi Okuno, Genrei Ohta, Takuya Kosaka, and Yusei Ohshima Copyright © 2016 Shuko Tokuriki et al. All rights reserved. MUC1 Immunohistochemical Expression as a Prognostic Factor in Gastric Cancer: Meta-Analysis Sun, 17 Apr 2016 13:39:07 +0000 http://www.hindawi.com/journals/dm/2016/9421571/ MUC1, a member of the mucin family, is expressed in tumors of various human organs and may function as an antiadhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis, and served as a potential biomarker of tumor progression in early gastric cancer. However, its prognostic significance in gastric cancer is still in dispute. We performed a meta-analysis to evaluate the relationship between MUC1 expression and prognosis of gastric cancer. A total of ten eligible studies with 834 cases and 548 controls were included. MUC1 positive cases were highly positive in intestinal-type carcinomas (OR = 1.76, 95% CI: 1.27–2.44, fixed-effect), higher rate of vascular invasion (OR = 1.64, 95% CI: 1.13–2.39, fixed-effect), and lymph node metastasis (OR = 2.10, 95% CI: 1.20–3.67, random-effect), as well as lower 5-year survival rate (HR = 0.27, 95% CI: 0.11–0.66, random-effect). However, the presence of MUC1 was not associated with gender, tumor size, histologic differentiation, and clinical stage. In summary, MUC1 is a prognostic factor in gastric cancer, which acts as a marker of poor outcome in patients with gastric cancer. Further clinical studies are needed to confirm the role of MUC1 in clinical practice. Xiao-Tong Wang, Fan-Biao Kong, Wei Mai, Lei Li, and Li-Ming Pang Copyright © 2016 Xiao-Tong Wang et al. All rights reserved. Long Noncoding RNAs as Novel Biomarkers Have a Promising Future in Cancer Diagnostics Sun, 10 Apr 2016 15:16:00 +0000 http://www.hindawi.com/journals/dm/2016/9085195/ Cancers have a high mortality rate due to lack of suitable specific early diagnosis tumor biomarkers. Emerging evidence is accumulating that lncRNAs (long noncoding RNAs) are involved in tumorigenesis, tumor cells proliferation, invasion, migration, apoptosis, and angiogenesis. Furthermore, extracellular lncRNAs can circulate in body fluids; they can be detected and strongly resist RNases. Many researchers have found that lncRNAs could be good candidates for tumor biomarkers and possessed high specificity, high sensitivity, and noninvasive characteristics. In this review, we summarize the detection methods and possible sources of circulating lncRNAs and outline the biological functions and expression level of the most significant lncRNAs in tissues, cell lines, and body fluids (whole blood, plasma, urine, gastric juice, and saliva) of different kinds of tumors. We evaluate the diagnostic performance of lncRNAs as tumor biomarkers. However, the biological functions and the mechanisms of circulating lncRNAs secretion have not been fully understood. The uniform normalization protocol of sample collection, lncRNAs extraction, endogenous control selection, quality assessment, and quantitative data analysis has not been established. Therefore, we put forward some recommendations that might be investigated in the future if we want to adopt lncRNAs in clinical practice. Ting Shi, Ge Gao, and Yingli Cao Copyright © 2016 Ting Shi et al. All rights reserved. Detection of OSR2, VAV3, and PPFIA3 Methylation in the Serum of Patients with Gastric Cancer Thu, 07 Apr 2016 11:10:36 +0000 http://www.hindawi.com/journals/dm/2016/5780538/ Aim. This study was to evaluate the diagnostic value of OSR2, VAV3, and PPFIA3 hypermethylation in gastric cancer (GC) patients. Patients and Methods. By using methylation-specific polymerase chain reaction (MSP), we detected the methylation status in tissue and serum samples from 48 gastric cancer (GC) patients and 25 normal individuals. Results. We found that OSR2, VAV3, and PPFIA3 were methylated in 70.8% (34/48), 54.2% (26/48), and 60.4% (29/48) of GC tissue, respectively. On the contrary, those genes were barely methylated in their paired paracancerous histological normal tissues (PCHNTs) (all values < 0.01). We next analyzed the methylated OSR2, VAV3, and PPFIA3 in serum DNA. Compared with 25 normal individuals, those three genes were significantly hypermethylated in GC patients serum samples (all values < 0.01). Regarding their diagnostic value in serum samples, the combined sensitivity of at least one positive among the three markers in serum was 83.3%, with a specificity of 88%. Conclusion. Our test suggested that methylation of OSR2, VAV3, and PPFIA3 genes in serum sample may offer a good alternative in a simple, promising, and noninvasive detection of GC. Wen-han Li, Zhang-jian Zhou, Tian-he Huang, Kun Guo, Wei Chen, Ying Wang, Hao Zhang, Yong-chun Song, and Dong-min Chang Copyright © 2016 Wen-han Li et al. All rights reserved. Salivary Markers for Periodontal and General Diseases Wed, 06 Apr 2016 08:05:16 +0000 http://www.hindawi.com/journals/dm/2016/9179632/ The determination of biomarkers in saliva is becoming an important part of laboratory diagnostics and the prediction of not only periodontal, but also other tissue and organ diseases. Biomarkers in saliva (e.g., enzymes, protein markers, or oxidative stress markers) can be used for activity determination and for periodontal disease prognosis. Saliva also contains many markers which can predict the risk of certain diseases (e.g., diabetes mellitus, cardiovascular, oncology, endocrinology, and psychiatric diseases). The study of salivary components proteomics clearly shows the relationship of periodontal diseases and diseases of distant systems, organs, or tissues. Stepan Podzimek, Lucie Vondrackova, Jana Duskova, Tatjana Janatova, and Zdenek Broukal Copyright © 2016 Stepan Podzimek et al. All rights reserved. Two tagSNPs rs352493 and rs3760908 within SIRT6 Gene Are Associated with the Severity of Coronary Artery Disease in a Chinese Han Population Mon, 28 Mar 2016 10:29:42 +0000 http://www.hindawi.com/journals/dm/2016/1628041/ SIRT6 has been demonstrated to exert protective effects on endothelial cells and is closely associated with lipid metabolism, glucose metabolism, and obesity, indicating an important role in the pathogenesis and progression of coronary artery disease (CAD). Nonetheless, the biological significance of SIRT6 variants on CAD is far to be elucidated. Here we aimed to investigate the influence of SIRT6 polymorphisms on individual susceptibility and severity of CAD. Multivariate logistic regression analysis exhibited no significant association between these five polymorphisms and CAD risk in the genotype and allele frequencies. However, we found that the rs352493 polymorphism in SIRT6 exhibited a significant effect on the severity of CAD; C allele (χ2 = 7.793, adjusted ) and the combined CC/CT genotypes (χ2 = 5.609, adjusted ) presented the greater CAD severity. In addition, A allele (χ2 = 5.208, adjusted ) and AA (χ2 = 4.842, adjusted ) of rs3760908 were also associated with greater CAD severity in Chinese subjects. Our data provided the first evidence that SIRT6 tagSNPs rs352493 and rs3760908 play significant roles in the severity of CAD in Chinese Han subjects, which might be useful predictors of the severity of CAD. Sai-sai Tang, Shun Xu, Jie Cheng, Meng-yun Cai, Lin Chen, Li-li Liang, Xi-li Yang, Can Chen, Xin-guang Liu, and Xing-dong Xiong Copyright © 2016 Sai-sai Tang et al. All rights reserved. The Prognostic Significance of Beta2 Microglobulin in Patients with Hemophagocytic Lymphohistiocytosis Sun, 27 Mar 2016 11:42:50 +0000 http://www.hindawi.com/journals/dm/2016/1523959/ Objective. To determine the prognostic significance of beta2 microglobulin (β2-m) concentrations in patients with hemophagocytic lymphohistiocytosis (HLH), a rare disorder caused by pathologic activation of the immune system. Patients and Methods. The study population consisted of 74 patients diagnosed with HLH and 35 healthy controls. Serum β2-m levels were measured using a latex agglutination photometric immunoassay. Results. Median serum β2-m levels were significantly higher in HLH patients than in healthy controls (4.05 versus 1.5 mg/L; ) and were significantly higher in patients with lymphoma associated hemophagocytic syndrome (LAHS) than in patients with benign disease-associated HLH (4.2 versus 3.3 mg/L; ). Higher serum β2-m levels were positively correlated with LAHS (), abnormal lactate dehydrogenase concentrations (), and hypoalbuminemia (). ROC analysis showed that overall survival (OS) was significantly shorter in LAHS patients with serum β2-m levels ≥4.03 mg/L compared to <4.03 mg/L (). Moreover, multivariate analysis showed that serum β2-m level was an independent prognostic of OS () in patients with LAHS. Conclusion. High serum β2-m levels and LAHS were associated with markedly poorer OS in patients with HLH. Serum β2-m concentration was a powerful and independent prognostic factor for OS in patients with LAHS. Tiantong Jiang, Xiurong Ding, and Weixing Lu Copyright © 2016 Tiantong Jiang et al. All rights reserved. Diagnostic Utility of Neuregulin for Acute Coronary Syndrome Thu, 24 Mar 2016 13:19:05 +0000 http://www.hindawi.com/journals/dm/2016/8025271/ The purpose of this study was to determine the diagnostic test characteristics of serum neuregulin-1β (NRG-1β) for the detection of acute coronary syndrome (ACS). We recruited emergency department patients presenting with signs and symptoms prompting an evaluation for ACS. Serum troponin and neuregulin-1β levels were compared between those who had a final discharge diagnosis of myocardial infarction (STEMI and NSTEMI) and those who did not, as well as those who more broadly had a final discharge diagnosis of ACS (STEMI, NSTEMI, and unstable angina). Of 319 study participants, 11% had evidence of myocardial infarction, and 19.7% had a final diagnosis of ACS. Patients with MI had median neuregulin levels of 0.16 ng/mL (IQR [0.16–24.54]). Compared to the median of those without MI, 1.46 ng/mL (IQR [0.16–15.02]), there was no significant difference in the distribution of results (). Median neuregulin levels for patients with ACS were 0.65 ng/mL (IQR [0.16–24.54]). There was no statistical significance compared to those without ACS who had a median of 1.40 ng/mL (IQR [0.16–14.19]) (). Neuregulin did not perform successfully as a biomarker for acute MI or ACS in the emergency department. Maame Yaa A. B. Yiadom, Jeremy Greenberg, Holly M. Smith, Douglas B. Sawyer, Dandan Liu, Jahred Carlise, Laura Tortora, and Alan B. Storrow Copyright © 2016 Maame Yaa A. B. Yiadom et al. All rights reserved. Prognostic and Predictive Values of Subcellular Localisation of RET in Renal Clear-Cell Carcinoma Tue, 22 Mar 2016 13:51:49 +0000 http://www.hindawi.com/journals/dm/2016/6870470/ Metastatic renal cell carcinoma (RCC) presents a poor prognosis and an unpredictable course. To date, no validated biomarkers can predict the outcome of RCC. Ongoing efforts are conducted to identify the molecular markers of RCC progression, as well as the targets for novel therapeutic approaches. RET is a tyrosine kinase receptor which has been investigated as a possible target in other cancers because it is involved in oncogenic activation. To evaluate the predictive and prognostic functions of RET in ccRCC, a tissue microarray study was conducted on 273 ccRCC patients. Results showed that both RET cytoplasmic and nuclear expression were independently associated with PFS and OS, and the combined RET cytoplasmic and nuclear statuses demonstrated that the ratio of high nuclear RET and cytoplasmic RET was the strongest predictor of both PFS and OS. The high cytoplasmic RET expression retained its independent poor prognostic value in targeted drug treated patients. The RET nuclear expression was associated with distant metastasis. Moreover, the RET nuclear expression was an independent predictor of ccRCC postoperative metastasis. In conclusion, RET may be useful in prognostication and can be used at initial diagnosis to identify patients with high potential to develop metastasis. Lei Wang, Yu Zhang, Yu Gao, Yang Fan, Luyao Chen, Kan Liu, Qingyu Meng, Chaofei Zhao, and Xin Ma Copyright © 2016 Lei Wang et al. All rights reserved. Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy Mon, 21 Mar 2016 08:27:38 +0000 http://www.hindawi.com/journals/dm/2016/8578064/ DNA methyltransferase 1 (DNMT1) plays a pivotal role in maintaining DNA methylation status. Polymorphisms of DNMT1 may modify the role of DNMT1 in prognosis of gastric cancer (GC). Our aim was to test whether polymorphisms of DNMT1 gene were associated with overall survival of GC. Four hundred and forty-seven GC patients who underwent radical tumorectomy were enrolled in the study. Five tagging SNPs (rs10420321, rs16999593, rs2228612, rs2228611, and rs2288349) of the DNMT1 gene were genotyped by TaqMan assays. Kaplan-Meier survival plots and Cox proportional hazard regression were used to analyze the associations between SNPs of DNMT1 and survival of GC. Patients carrying rs2228611 GA/AA genotype tended to live longer than those bearing the GG genotype (HR 0.68, 95% CI: 0.51–0.91, ). Further multivariate Cox regression analysis showed that rs2228611 was an independent prognostic factor (GA/AA versus GG: OR 0.67, 95% CI 0.49–0.91, ). Nevertheless, other SNPs did not show any significant associations with survival of GC. Polymorphisms of the DNMT1 gene may affect overall survival of GC. The SNP rs2228611 has the potentiality to serve as an independent prognostic marker for GC patients. Zhifang Jia, Xing Wu, Donghui Cao, Chuan Wang, Lili You, Meishan Jin, Simin Wen, Xueyuan Cao, and Jing Jiang Copyright © 2016 Zhifang Jia et al. All rights reserved. Prognostic Value of Neutrophil-Related Factors in Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin-Based Concurrent Chemoradiotherapy Sun, 20 Mar 2016 14:30:48 +0000 http://www.hindawi.com/journals/dm/2016/3740794/ The aim of this study was to explore the relationship between neutrophil-related factors, including neutrophil-lymphocyte ratio (NLR) and the responses of neutrophil to granulocyte colony-stimulating factors (RNG), and the prognosis of patients with locally advanced cervical squamous cell carcinoma (LACSCC) undergoing cisplatin-based concurrent chemoradiotherapy (CCCRT). A total of sixty LACSCC patients were enrolled in this study. We analyzed the association of NLR or RNG with clinicopathologic characteristics of these patients. The prognostic factors were evaluated by univariate and multivariate survival analysis. The optimal cut-off value of the NLR was determined to be 2.0 for the overall survival (OS). A higher level of the NLR was associated with younger age () and higher baseline platelet count (). NLR was identified to be the only independent prognostic factor for OS by multivariate analysis (). The median RNG was 3.01, with a range of 1.19–16.84. RNG level was significantly associated with lymph node metastasis of these patients (). And higher RNG was identified as being a closely independent poor prognostic factor for OS (). This study showed that NLR and RNG may be used as potential biomarkers for survival prediction in patients with LACSCC receiving CCCRT. Yan-Yang Wang, Zhou-Lan Bai, Jian-Li He, Yan Yang, Ren Zhao, Ping Hai, and Hong Zhe Copyright © 2016 Yan-Yang Wang et al. All rights reserved. Corrigendum to “Chaperonin-Containing t-Complex Protein-1 Subunit β as a Possible Biomarker for the Phase of Glomerular Hyperfiltration of Diabetic Nephropathy” Wed, 16 Mar 2016 12:48:59 +0000 http://www.hindawi.com/journals/dm/2016/8653290/ Chung-Ze Wu, Li-Chien Chang, Yuh-Feng Lin, Yi-Jen Hung, Dee Pei, and Jin-Shuen Chen Copyright © 2016 Chung-Ze Wu et al. All rights reserved. Diagnosis and Prognostic Significance of c-Met in Cervical Cancer: A Meta-Analysis Wed, 16 Mar 2016 07:42:24 +0000 http://www.hindawi.com/journals/dm/2016/6594016/ Objective. A meta-analysis was conducted to analyze c-Met expression in cervical cancer. Methods. Articles related to our study were retrieved from PubMed, Elsevier, and China National Knowledge Infrastructure. State 12.0 was used for literature review, data extraction, and meta-analysis. The random-effects model and fixed-effects model were utilized to pool the relative ratio based on the heterogeneity test in the meta-analysis. Results. Nine studies that include data of 685 cervical carcinoma tissues were analyzed. However, three studies did not thoroughly discuss c-Met expression in nonneoplastic cervical tissue; thus, only six studies involving 364 patients and 228 nonneoplastic cervical tissues were included in the review. c-Met expression was higher in cervical cancer (60.99%) than in nonneoplastic cervical tissue (19.74%). Cervical carcinoma, cervical intraepithelial neoplasm, and normal cervical tissue were also examined. Results showed that increasing malignancy resulted in elevated c-Met expression. The relationship between c-Met expression and clinicopathologic features was also evaluated. c-Met expression correlated with disease-free survival, lymph node involvement, and lymphovascular space invasion. No statistical difference was observed between c-Met expression and other clinicopathological factors. Conclusions. c-Met is a potential diagnostic and prognostic indicator of cervical cancer. Jifeng Peng, Shengnan Qi, Ping Wang, Wanyu Li, Chunxia Liu, and Feng Li Copyright © 2016 Jifeng Peng et al. All rights reserved. Analysis of Urinary Prostate-Specific Antigen Glycoforms in Samples of Prostate Cancer and Benign Prostate Hyperplasia Tue, 15 Mar 2016 09:41:25 +0000 http://www.hindawi.com/journals/dm/2016/8915809/ Glycans of prostate-specific antigen (PSA) in prostate cancer were found to be different from that in benign disease. It is difficult to analyze heterogeneous PSA glycoforms in each individual specimen because of low protein abundance and the limitation of detection sensitivity. We developed a method for prostate cancer diagnosis based on PSA glycoforms. Specific glycoforms were screened in each clinical sample based on liquid chromatography-tandem mass spectrometry with ion accumulation. To look for potential biomarkers, normalized abundance of each glycoform in benign prostate hyperplasia (BPH) and in prostate cancer was evaluated. The PSA glycoform, Hex5HexNAc4NeuAc1dHex1, and monosialylated, sialylated, and unfucosylated glycoforms differed significantly between the prostate cancer and BPH samples. The detection sensitivity (87.5%) and specificity (60%) for prostate cancer identification are higher than those of the serum PSA marker. As low as 100 amol PSA could be detected with the ion accumulation method which has not been reported before. The improved detection specificity can help reduce unnecessary examinations. Chun-Jen Hsiao, Tzong-Shin Tzai, Chein-Hung Chen, Wen-Horng Yang, and Chung-Hsuan Chen Copyright © 2016 Chun-Jen Hsiao et al. All rights reserved. CD38 Expression in a Subset of Memory T Cells Is Independent of Cell Cycling as a Correlate of HIV Disease Progression Mon, 14 Mar 2016 07:58:26 +0000 http://www.hindawi.com/journals/dm/2016/9510756/ In order to determine if the expression of the activation marker CD38 can correlate with HIV disease progression independently of cycling, we performed a cluster-based multivariate correlation analysis of total circulating CD4+ T cell counts and viral loads with frequencies of CD38 and Ki67 expression on CD4+ lymphocytes from patients with untreated HIV infection, stratified in maturation subpopulations, and subpopulation subsets defined by the expression of CXCR5, CXCR3, and CCR4. The frequencies of the activated phenotypes %CD38+ Ki67− and %CD38+ Ki67+ of the CXCR5− CXCR3− CCR4+ (“pre-Th2”) central memory () cell subset clustered together, comprising a significant negative correlate of total circulating CD4+ T cell counts and a positive correlate of viral load in multivariate analysis. Frequency of cycling-uncoupled CD38 expression in “pre-Th2” cells was a negative correlate of total circulating CD4+ T cell counts in univariate analysis, which was not the case of their %CD38+ Ki67+. CXCR5+ CXCR3− CCR4−   cells were underrepresented in patients, and their absolute counts correlated negatively with their %CD38+ Ki67− but not with their % CD38+ Ki67+. Our results may imply that CD38 expression either reflects or participates in pathogenic mechanisms of HIV disease independently of cell cycling. Daniela Würsch, Christopher E. Ormsby, Dámaris P. Romero-Rodríguez, Gustavo Olvera-García, Joaquín Zúñiga, Wei Jiang, Santiago Pérez-Patrigeon, and Enrique Espinosa Copyright © 2016 Daniela Würsch et al. All rights reserved. Quantitative ELISA-Like Immunohistochemistry of Fibroblast Growth Factor 23 in Diagnosis of Tumor-Induced Osteomalacia and Clinical Characteristics of the Disease Sun, 13 Mar 2016 11:16:02 +0000 http://www.hindawi.com/journals/dm/2016/3176978/ Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic disorder and fibroblast growth factor 23 (FGF23) plays a key role in its pathogenesis. This study was conducted to describe a novel FGF23 detecting procedure and describe clinical features of the disease. Fourteen TIO cases were retrieved and FGF23 expression was measured by quantitative ELISA-like immunohistochemistry using formalin-fixed and paraffin-embedded tissues. As summarized from 14 TIO cases, clinical features of TIO were long-standing history of osteomalacia, hypophosphatemia, and urinary phosphate wasting. The associated tumors were mostly benign phosphaturic mesenchymal tumors mixed connective tissue variant (PMTMCT) which could be located anywhere on the body, and most of them could be localized by conventional examinations and octreotide scanning. By quantitative ELISA-like immunohistochemistry, all the 14 TIO cases had high FGF23 expression (median 0.69, 25%–75% interquartile 0.57–1.10, compared with 26 non-TIO tumors of median 0.07, 25%–75% interquartile 0.05–0.11, ). The quantitative ELISA-like immunohistochemistry was a feasible and reproducible procedure to detect the high FGF23 expression in formalin-fixed and paraffin-embedded biopsies or specimens. Since TIO was often delay-diagnosed or misdiagnosed, clinicians and pathologists should be aware of TIO and PMTMCT, respectively. Fangke Hu, Chengying Jiang, Qiang Zhang, Huaiyin Shi, Lixin Wei, and Yan Wang Copyright © 2016 Fangke Hu et al. All rights reserved.