Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Proteomic Analysis of Serum and Urine of HIV-Monoinfected and HIV/HCV-Coinfected Patients Undergoing Long Term Treatment with Nevirapine Wed, 17 Dec 2014 00:10:34 +0000 http://www.hindawi.com/journals/dm/2014/315824/ Nevirapine (NVP) is an effective nonnucleoside reverse transcriptase inhibitor (NNRTI) of particular interest as it is often used in resource limited countries. However, one of the main concerns with the use of NVP is hepatotoxicity and elevation of liver enzymes as a consequence of highly active antiretroviral therapy (HAART) containing NVP is more often reported in HIV patients coinfected with hepatitis C virus than in HIV-monoinfected patients. To discover possible markers of NVP induced hepatotoxicity, serum and urine samples from twenty-five HIV or HIV/HCV patients, all of whom had received NVP continuously for at least four months, and healthy controls were subjected to in-solution or in-gel proteomic analysis. A total of 83 differentially regulated proteins consisted of 34 proteins identified in serum by in-solution analysis, 2 proteins identified from serum in a 2D gel electrophoresis analysis, and 47 proteins identified in urine in an in-solution analysis. Three proteins, namely, haptoglobin, Rho-related BTB domain containing protein 3, and death-associated protein kinase 3, were selected for further validation by Western blot analysis and results showed that haptoglobin has potential for further development as an additional marker of NVP induced hepatotoxicity. Jeerang Wongtrakul, Thananya Thongtan, Sittiruk Roytrakul, Benjawan Kumrapich, Kanokwan Janphen, Jutarat Praparattanapan, Khuanchai Supparatpinyo, and Duncan R. Smith Copyright © 2014 Jeerang Wongtrakul et al. All rights reserved. Red Cell Distribution Width Is Associated with Presence, Stage, and Grade in Patients with Renal Cell Carcinoma Tue, 16 Dec 2014 07:16:20 +0000 http://www.hindawi.com/journals/dm/2014/860419/ It has been reported that red blood cell width (RDW) is a marker associated with the presence and adverse outcomes of various diseases. However, no data are available on the correlation of RDW with presence, stage, and grade in patients with renal cell carcinoma (RCC) yet. By retrospectively analyzing clinical and laboratory data at baseline of histologically confirmed RCC cases and controls, the present study demonstrated that the RDW values were significantly higher in patients with RCC than those in controls, and the baseline RDW value was independently associated with the presence of RCC. Besides, the data revealed a positive association between RCC stage and grade and the level of RDW. These findings may have important clinical implications due to future application using a RDW value in predicting RCC. Fang-Ming Wang, Gongjun Xu, Yan Zhang, and Lu-Lin Ma Copyright © 2014 Fang-Ming Wang et al. All rights reserved. Mig-6 Gene Knockout Induces Neointimal Hyperplasia in the Vascular Smooth Muscle Cell Wed, 10 Dec 2014 10:26:46 +0000 http://www.hindawi.com/journals/dm/2014/549054/ Although advances in vascular interventions can reduce the mortality associated with cardiovascular disease, neointimal hyperplasia remains a clinically significant obstacle limiting the success of current interventions. Identification of signaling pathways involved in migration and proliferation of vascular smooth muscle cells (SMCs) is an important approach for the development of modalities to combat this disease. Herein we investigate the role of an immediate early response gene, mitogen-inducible gene-6 (Mig-6), in the development of neointimal hyperplasia using vascular smooth muscle specific Mig-6 knockout mice. We induced endoluminal injury to one side of femoral artery by balloon dilatation in both Mig-6 knockout and control mice. Four weeks following injury, the artery of Mig-6 knockout mice demonstrated a 5.3-fold increase in the neointima/media ratio compared with control mice . In addition, Mig-6 knockout vascular SMCs displayed an increase in both cell migration and proliferation compared with wild-type SMCs. Taken together, our data suggest that Mig-6 plays a critical role in the development of atherosclerosis. This finding provides new insight into the development of more effective ways to treat and prevent neointimal hyperplasia, particularly in-stent restenosis after percutaneous vascular intervention. Ju Hee Lee, Sorim Choung, Ji Min Kim, Jung Uee Lee, Koon Soon Kim, Hyun Jin Kim, Jae-Wook Jeong, and Bon Jeong Ku Copyright © 2014 Ju Hee Lee et al. All rights reserved. Serum Clusterin as a Tumor Marker and Prognostic Factor for Patients with Esophageal Cancer Wed, 10 Dec 2014 06:55:00 +0000 http://www.hindawi.com/journals/dm/2014/168960/ Background. Recent studies have revealed that clusterin is implicated in many physiological and pathological processes, including tumorigenesis. However, the relationship between serum clusterin expression and esophageal squamous cell carcinoma (ESCC) is unclear. Methods. The serum clusterin concentrations of 87 ESCC patients and 136 healthy individuals were examined. An independent-samples Mann-Whitney test was used to compare serum clusterin concentrations of ESCC patients to those of healthy controls. Univariate analysis was conducted using the log-rank test and multivariate analyses were performed using the Cox proportional hazards model. Results. In healthy controls, the mean clusterin concentration was  μg/mL, while in the ESCC patients, the mean clusterin concentration was higher at  μg/mL (). The 1-, 2-, and 4-year survival rates for the 87 ESCC patients were 89.70%, 80.00%, and 54.50%. Serum clusterin had an optimal diagnostic cut-off point (serum clusterin concentration = 335.5 μg/mL) for esophageal squamous cell carcinoma with sensitivity of 71.26% and specificity of 77.94%. And higher serum clusterin concentration (>500 μg/mL) indicated better prognosis (). Conclusions. Clusterin may play a key role during tumorigenesis and tumor progression of ESCC and it could be applied in clinical work as a tumor marker and prognostic factor. Wei Guo, Xiao Ma, Christine Xue, Jianfeng Luo, Xiaoli Zhu, Jiaqing Xiang, Bo Lu, and Hecheng Li Copyright © 2014 Wei Guo et al. All rights reserved. Methylation of DLEC1 Promoter Is a Predictor for Recurrence in Chinese Patients with Gastric Cancer Tue, 09 Dec 2014 11:57:32 +0000 http://www.hindawi.com/journals/dm/2014/804023/ Purpose. To investigate promoter methylation in the deleted in lung and esophageal cancer 1 (DLEC1) gene in Chinese patients with gastric cancer. Methods. A total of 227 patients with gastric cancer were enrolled. The methylations of the promoter regions of DLEC1 and ACTB were determined using quantitative methylation-specific PCR. The DLEC1 methylation was compared to the clinicopathological variables of gastric cancer. Results. DLEC1 methylation was not associated with the clinicopathological variables of gastric cancer. Patients with DLEC1-hypermethylated gastric cancer had significantly higher recurrence rate than those with DLEC1-hypomethylated gastric cancer (; ). Conclusions. Methylation of DELC1 promoter may be a valuable predictor for recurrence in Chinese patients with gastric cancer. Xiaobing Ye, Gang Feng, Nanlin Jiao, Chun Pu, Guohai Zhao, and Guoping Sun Copyright © 2014 Xiaobing Ye et al. All rights reserved. Peroxisome Proliferator-Activated Receptors Family Is Involved in the Response to Treatment and Mild Clinical Course in Patients with Ulcerative Colitis Mon, 08 Dec 2014 07:16:13 +0000 http://www.hindawi.com/journals/dm/2014/932530/ Background. PPARs play an important role in the regulation of intestinal inflammation. Methods. We included a total of 46 UC patients and 31 controls. The gene expression of PPARs was measured by RT-PCR and protein expression by immunohistochemistry. Results. PPARα gene expression was significantly decreased in patients with active UC compared with remission UC group and controls . We found that low gene expression of PPARα in mucosa confers a higher risk of UC activity (, OR = 22.6). We observed an increase of PPARα expression in patients with UC who were treated with 5-aminosalicylates compared with those who received any other combined therapy (, OR = 0.08). PPARγ gene expression was decreased in the active UC group compared with UC in remission and control group . An increased expression of PPARγ gene was associated with mild clinical course of the disease (, OR = 0.05). No gene expression of PPARβ/δ was found in the colonic mucosa from UC patients and controls. Conclusion. Our results suggest that patients with high gene expression of PPARs have a better response to medical treatment and a mild clinical course of the disease. J. K. Yamamoto-Furusho, M. Jacintez-Cazares, J. Furuzawa-Carballeda, and G. Fonseca-Camarillo Copyright © 2014 J. K. Yamamoto-Furusho et al. All rights reserved. RNA-Seq Data Mining: Downregulation of NeuroD6 Serves as a Possible Biomarker for Alzheimer’s Disease Brains Mon, 08 Dec 2014 00:10:22 +0000 http://www.hindawi.com/journals/dm/2014/123165/ Alzheimer’s disease (AD) is the most common cause of dementia worldwide with no curative therapies currently available. Previously, global transcriptome analysis of AD brains by microarray failed to identify the set of consistently deregulated genes for biomarker development of AD. Therefore, the molecular pathogenesis of AD remains largely unknown. Whole RNA sequencing (RNA-Seq) is an innovative technology for the comprehensive transcriptome profiling on a genome-wide scale that overcomes several drawbacks of the microarray-based approach. To identify biomarker genes for AD, we analyzed a RNA-Seq dataset composed of the comprehensive transcriptome of autopsized AD brains derived from two independent cohorts. We identified the core set of 522 genes deregulated in AD brains shared between both, compared with normal control subjects. They included downregulation of neuronal differentiation 6 (NeuroD6), a basic helix-loop-helix (bHLH) transcription factor involved in neuronal development, differentiation, and survival in AD brains of both cohorts. We verified the results of RNA-Seq by analyzing three microarray datasets of AD brains different in brain regions, ethnicities, and microarray platforms. Thus, both RNA-Seq and microarray data analysis indicated consistent downregulation of NeuroD6 in AD brains. These results suggested that downregulation of NeuroD6 serves as a possible biomarker for AD brains. Jun-ichi Satoh, Yoji Yamamoto, Naohiro Asahina, Shouta Kitano, and Yoshihiro Kino Copyright © 2014 Jun-ichi Satoh et al. All rights reserved. CLCA2 as a Novel Immunohistochemical Marker for Differential Diagnosis of Squamous Cell Carcinoma from Adenocarcinoma of the Lung Sun, 07 Dec 2014 07:28:34 +0000 http://www.hindawi.com/journals/dm/2014/619273/ Recent progress in targeted therapy for lung cancer has revealed that accurate differential diagnosis between squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the lung is essential. To identify a novel immunohistochemical marker useful for differential diagnosis between the two subtypes of lung cancer, we first selected 24 SCC-specific genes and 6 ADC-specific genes using data (case number, 980) from the Cancer Genome Atlas (TCGA) database. Among the genes, we chose the CLCA2 gene, which is involved in chloride conductance and whose protein expression in lung cancer is yet to be characterized, and evaluated its protein expression status in 396 cases of primary lung cancer at Hamamatsu University Hospital. Immunohistochemical analysis revealed a significantly higher CLCA2 expression level in the SCCs than in the ADCs and also a significantly higher frequency of CLCA2 protein expression in the SCCs (104/161, 64.6%) as compared with that in the ADCs (2/235, 0.9%) ; sensitivity 64.6%, specificity 99.1%). The CLCA2 protein expression status was associated with the histological tumor grade in the SCCs. These results suggest that CLCA2 might be a novel excellent immunohistochemical marker for differentiating between primary SCC and primary ADC of the lung. Kazuya Shinmura, Hisaki Igarashi, Hisami Kato, Yuichi Kawanishi, Yusuke Inoue, Satoki Nakamura, Hiroshi Ogawa, Takashi Yamashita, Akikazu Kawase, Kazuhito Funai, and Haruhiko Sugimura Copyright © 2014 Kazuya Shinmura et al. All rights reserved. Transporter TAP1-637G and Immunoproteasome PSMB9-60H Variants Influence the Risk of Developing Vitiligo in the Saudi Population Sun, 07 Dec 2014 00:10:47 +0000 http://www.hindawi.com/journals/dm/2014/260732/ We evaluated whether TAP1-rs1135216 (p.637D>G) and PSMB9-rs17587 (p.60R>H) were significantly associated with the risk and severity of vitiligo among Saudi patients. One hundred seventy-two subjects were genotyped for the TAP1-rs1135216 and PSMB9-rs17587 variants using endonuclease digestions of amplified genomic DNA. The TAP1-rs1135216 and PSMB9-rs17587 mutant alleles were strongly associated with vitiligo, with odds ratios showing five fold and two fold risks ( and , resp.). In TAP1-rs1135216, the 637G mutant allele was more frequent in cases (74%) than in healthy controls. In cases, the 60H mutant allele PSMB9-rs17587 was less frequent (42%) than the wild-type 60R allele (58%). Vitiligo vulgaris was the most common type of disease, associated with the DG (55%) and GG (46%) genotypes for rs1135216 and with the RH genotype (59%) for rs17587. The heterozygous 637DG and 60RH genotypes were each linked with active phenotypes in 64% of cases. In conclusion, the TAP1-rs1135216 and PSMB9-rs17587 variants are significantly associated with vitiligo, and even one copy of these mutant alleles can influence the risk among Saudis. Vitiligo vulgaris is associated with genotypes containing the mutant G and H alleles. Nasser Attia Elhawary, Neda Bogari, Essam Hussien Jiffri, Mona Rashad, Abdulhamid Fatani, and Mohammed Tayeb Copyright © 2014 Nasser Attia Elhawary et al. All rights reserved. Genetic Polymorphisms Involved in Folate Metabolism and Maternal Risk for Down Syndrome: A Meta-Analysis Thu, 04 Dec 2014 00:10:13 +0000 http://www.hindawi.com/journals/dm/2014/517504/ Inconclusive results of the association between genetic polymorphisms involved in folate metabolism and maternal risk for Down syndrome (DS) have been reported. Therefore, this meta-analysis was conducted. We searched electronic databases through May, 2014, for eligible studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association, which was estimated by fixed or random effects models. Heterogeneity among studies was evaluated using Q-test and I2 statistic. Subgroup and sensitivity analyses were also conducted. Publication bias was estimated using Begg’s and Egger’s tests. A total of 17 case-controls studies were included. There was evidence for an association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS. In the subgroup analysis, increased maternal risk for DS was found in Caucasians. Additionally, the polymorphic heterozygote MTHFD1 1958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies conformed to Hardy-Weinberg equilibrium. Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.844ins68, no significant associations have been found, neither in the overall analyses nor in the stratified analyses by ethnicity. In conclusion, our meta-analysis suggested that the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS. Daniella Balduino Victorino, Moacir Fernandes de Godoy, Eny Maria Goloni-Bertollo, and Érika Cristina Pavarino Copyright © 2014 Daniella Balduino Victorino et al. All rights reserved. ZEB1 Expression in Endometrial Biopsy Predicts Lymph Node Metastases in Patient with Endometrial Cancer Wed, 03 Dec 2014 00:10:18 +0000 http://www.hindawi.com/journals/dm/2014/680361/ Purpose. The purpose of this study was to analyze the expression of zinc-finger E-box-binding homeobox 1 (ZEB1) in endometrial biopsy and its correlation with preoperative characteristics, including lymph node metastases in patient with endometrial cancer. Methods. Using quantitative RT-PCR, ZEB1 expressions in endometrial biopsy from 452 patients were measured. The relationship between ZEB1 expression and preoperative characteristics was analyzed. Results. ZEB1 expressions were significantly associated with subtype, grade, myometrial invasion, and lymph node metastases. Lymph node metastases could be identified with a sensitivity of 57.8% at specificity of 74.1% by ZEB1 expression in endometrial biopsy. Based on combination of preoperative characteristics and ZEB1 expression, lymph node metastases could be identified with a sensitivity of 62.1% at specificity of 96.2% prior to hysterectomy. Conclusion. ZEB1 expression in endometrial biopsy could help physicians to better predict the lymph node metastasis in patients with endometrial cancer prior to hysterectomy. Gang Feng, Xiangming Wang, Xiaozhi Cao, Lijuan Shen, and Jiansheng Zhu Copyright © 2014 Gang Feng et al. All rights reserved. Haptoglobin Duplicon, Hemoglobin, and Vitamin C: Analyses in the British Women’s Heart and Health Study and Caerphilly Prospective Study Sun, 30 Nov 2014 00:10:24 +0000 http://www.hindawi.com/journals/dm/2014/529456/ Background. Haptoglobin acts as an antioxidant by limiting peroxidative tissue damage by free hemoglobin. The haptoglobin gene allele Hp2 comprises a 1.7 kb partial duplication. Relative to allele Hp1, Hp2 carriers form protein multimers, suboptimal for hemoglobin scavenging. Objective. To examine the association of haptoglobin genotype with a range of phenotypes, with emphasis on vitamin C and hemoglobin levels. Methods. We applied a quantitative PCR assay for the duplication junction to two population cohorts including 2747 British women and 1198 British men. We examined the association of haptoglobin duplicon copy number with hemoglobin and vitamin C and used the copy number to complete a phenome scan. Results. Hemoglobin concentrations were greater in those with Hp2,2 genotype, in women only (Hp1,1 13.45 g/dL, Hp1,2 13.49 g/dL, Hp2,2 13.61 g/dL; ), though statistically there was no evidence of a difference between the sexes ( value = 1.2, ). Haptoglobin genotype was not associated with vitamin C or any other phenotype in either cohort. Conclusions. Our results do not support association of haptoglobin genotype with vitamin C or with other phenotypes measured in two population cohorts. The apparent association between haptoglobin genotype and hemoglobin in the women’s cohort merits further investigation. Philip A. I. Guthrie, Mohammad R. Abdollahi, Tom Gaunt, Debbie A. Lawlor, Yoav Ben-Shlomo, John Gallacher, George Davey Smith, Ian N. M. Day, and Santiago Rodriguez Copyright © 2014 Philip A. I. Guthrie et al. All rights reserved. High SHIP2 Expression Indicates Poor Survival in Colorectal Cancer Mon, 24 Nov 2014 10:11:22 +0000 http://www.hindawi.com/journals/dm/2014/218968/ SH2-containing inositol 5′-phosphatase 2 (SHIP2), which generally regulates insulin signaling, cytoskeleton remodeling, and receptor endocytosis, has been suggested to play a significant role in tumor development and progression. However, the associations between SHIP2 expression and the clinical features to evaluate its clinicopathologic significance in colorectal cancer (CRC) have not been determined yet. In the present study, one-step quantitative real-time polymerase chain reaction (qPCR) test and immunohistochemistry (IHC) analysis with CRC tissue microarrays (TMA) were employed to evaluate the mRNA and protein expression of SHIP2 in CRC. The results showed that SHIP2 expression in the mRNA and protein levels was significantly higher in CRC tissues than that in corresponding noncancerous tissues (both ). The expression of SHIP2 protein in CRC was related to lymph node metastasis , distant metastasis , and overall survival . Kaplan-Meier method and Cox multifactor analysis suggested that high SHIP2 protein level and positive distant metastasis were critically associated with the unfavorable survival of CRC patients. The findings suggested that SHIP2 may be identified as a useful prognostic marker in CRC and targeting CRC may provide novel strategy for CRC treatment. Ju Yang, Maoying Fu, Yaoguang Ding, Yajing Weng, Weifei Fan, Xiaolin Pu, Zhijun Ge, Feng Zhan, Huihui Ni, Wei Zhang, Feng Jin, Ning Xu, Jiang Li, Liang Qiu, Jun Wang, and Xuefeng Gu Copyright © 2014 Ju Yang et al. All rights reserved. The Use of Humoral Responses as a Marker of CMV Burden in HIV Patients on ART Requires Consideration of T-Cell Recovery and Persistent B-Cell Activation Sun, 23 Nov 2014 11:38:11 +0000 http://www.hindawi.com/journals/dm/2014/947432/ Objectives. Elevated humoral responses to cytomegalovirus (CMV) associate with increased risk of cardiovascular disease (CVD) in HIV patients on antiretroviral therapy (ART). To better understand the persistence of CMV humoral responses in relation to CVD, we determined trends in CMV antibody levels over the first 10 years on ART. Design. We describe longitudinal analyses of plasma from 13 HIV patients commencing ART with <210 CD4 T-cells/µL and 27 controls. Antibodies reactive with CMV (fibroblast lysate, gB and IE-1 antigens), EBV-VCA, and HIVgp41 were quantitated. B-cell activation was assessed via total IgG and sBAFF. Inflammation was assessed via sTNF-RI and sCD14. Results. Amongst CMV seropositive HIV patients, levels of antibody reactive with CMV and EBV-VCA peaked after 1 year on ART. Levels of total IgG, sCD14, and sTNF-RI declined to approximate those in controls after 10 years, but sBAFF , EBV-VCA , and CMV antibodies remained elevated. A strong correlation between sBAFF and CMVgB antibody was seen at 10 years and verified in a second cohort. Conclusions. CMV antibody titres peak on ART and remain high. A correlation between CMV antibody and sBAFF suggests a role for HIV-induced B-cell pathology that may affect its use as a marker of CMV burden. Samantha J. Brunt, Silvia Lee, Lloyd D’Orsogna, Christine Bundell, Sally Burrows, and Patricia Price Copyright © 2014 Samantha J. Brunt et al. All rights reserved. Pleural Fluid Mesothelin as an Adjunct to the Diagnosis of Pleural Malignant Mesothelioma Sun, 23 Nov 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/413946/ Rationale. The diagnosis of pleural malignant mesothelioma (MM) by effusion cytology may be difficult and is currently controversial. Effusion mesothelin levels are increased in patients with MM but the clinical role of this test is uncertain. Objectives. To determine the clinical value of measuring mesothelin levels in pleural effusion supernatant to aid diagnosis of MM. Methods and Measurements. Pleural effusion samples were collected prospectively from 1331 consecutive patients. Mesothelin levels were determined by commercial ELISA in effusions and their relationship to concurrent pathology reporting and final clinical diagnosis was determined. Results. 2156 pleural effusion samples from 1331 individuals were analysed. The final clinical diagnosis was 183 MM, 436 non-MM malignancy, and 712 nonmalignant effusions. Effusion mesothelin had a sensitivity of 67% for MM at 95% specificity. Mesothelin was elevated in over 47% of MM cases in effusions obtained before definitive diagnosis of MM was established. In the setting of inconclusive effusion cytology, effusion mesothelin had a positive predictive value of 79% for MM and 94% for malignancy. Conclusions. A mesothelin-positive pleural effusion, irrespective of the identification of malignant cells, indicates the likely presence of malignancy and adds weight to the clinical rationale for further investigation to establish a malignant diagnosis. Jenette Creaney, Amanda Segal, Nola Olsen, Ian M. Dick, A. W(Bill) Musk, Steven J. Skates, and Bruce W. Robinson Copyright © 2014 Jenette Creaney et al. All rights reserved. Residual Salivary Secretion Ability May Be a Useful Marker for Differential Diagnosis in Autoimmune Diseases Thu, 20 Nov 2014 07:19:21 +0000 http://www.hindawi.com/journals/dm/2014/534261/ Background. We have elucidated decreased resting salivary flow in approximately 60% of patients with autoimmune diseases not complicated by Sjögren syndrome (SjS). In this study, salivary stimulation tests using capsaicin were performed to examine residual salivary secretion ability in patients with autoimmune diseases. Materials and Methods. Fifty-eight patients were divided into three groups: patients with primary or secondary SjS (SjS group), patients with systemic sclerosis not complicated by SjS (SSc group), and patients with other autoimmune diseases (non-SjS/non-SSc group). Simple filter paper and filter paper containing capsaicin were used to evaluate salivary flow rates. Results. Resting salivary flow rates were significantly lower in the SjS and SSc groups than in the non-SjS/non-SSc group but did not differ significantly between the SjS and SSc groups. Capsaicin-stimulated salivary flow rates were significantly lower in the SjS and SSc groups than in the non-SjS/non-SSc group, but not significantly different between the SjS and SSc groups. In the non-SjS/non-SSc group, salivary flow rates increased after capsaicin stimulation to the threshold level for determination of salivary gland dysfunction, whereas no improvement was observed in the SjS and SSc groups. Conclusion. Residual salivary secretion ability may be a useful marker for differential diagnosis in autoimmune diseases. Etsuko Maeshima, Hiroya Koshiba, Kanako Furukawa, Shinichiro Maeshima, and Wataru Sakamoto Copyright © 2014 Etsuko Maeshima et al. All rights reserved. MicroRNA Expression Profiling in PBMCs: A Potential Diagnostic Biomarker of Chronic Hepatitis C Tue, 18 Nov 2014 12:39:42 +0000 http://www.hindawi.com/journals/dm/2014/367157/ The expression levels of miR-16, miR-193b, miR-199a, miR-222, and miR-324 in PBMCs were significantly higher in CHC patients compared with healthy controls and significantly different between CHC patients with HCV genotype 1 (GT-1) and non-genotype-1 (non-GT-1). Multivariate logistic regression analysis also showed that patients with high expression levels of the six target miRNAs had an approximately 7.202-fold risk of CHC compared with those with low expression levels of the target miRNAs. We concluded that the expression levels of miR-16, miR-193b, miR-199a, miR-222, and miR-324 target miRNAs in PBMCs of CHC may act as significant risk biomarkers for the development of CHC. Chiu-Chun Chang, Chun-Che Lin, Wan-Ling Hsieh, Hsin-Wu Lai, Chia-Hsun Tsai, and Ya-Wen Cheng Copyright © 2014 Chiu-Chun Chang et al. All rights reserved. Neutrophil-to-Lymphocyte Ratio as a Predictor of Response to Peginterferon plus Ribavirin Therapy for Chronic Hepatitis C Tue, 18 Nov 2014 11:22:58 +0000 http://www.hindawi.com/journals/dm/2014/462958/ We aimed to determine whether neutrophil-to-lymphocyte ratio (NLR) could be a predictor of antiviral response in chronic hepatitis C patients. A total of 602 consecutive patients (genotype 1, ; genotype 2, ; others/unknown, ) receiving response-guided therapy with peginterferon plus ribavirin were recruited. NLR was related to clinical and virological features and to treatment outcome. Rapid virological response (RVR) and sustained virological response (SVR) were achieved in 436 (73%) and 458 (76%) of the patients, respectively. Higher NLR (≥1.42) was found to be associated with higher prevalence of DM () and higher hepatitis C viral load () and white cell count (). NLR was significantly lower in patients with RVR and SVR compared to those without ( and 0.034, resp.). However, NLR was not an independent factor by multivariate analysis. In the subgroup analysis, higher NLR (≥1.42) (odds ratio, 0.494, ) was an independent poor predictor of SVR in genotype 2 patients but was not in genotype 1 patients. In conclusion, NLR is a simple and easily accessible marker to predict response to peginterferon plus ribavirin therapy for chronic hepatitis C genotype 2. Ming-Te Kuo, Tsung-Hui Hu, Sheng-Nan Lu, Chao Hung Hung, Jing-Houng Wang, Chien-Hung Chen, Yi-Chun Chiu, and Chuan-Mo Lee Copyright © 2014 Ming-Te Kuo et al. All rights reserved. Influence of Adiposity-Related Genetic Markers in a Population of Saudi Arabians Where Other Variables Influencing Obesity May Be Reduced Mon, 17 Nov 2014 13:20:23 +0000 http://www.hindawi.com/journals/dm/2014/758232/ Large scale studies in Europeans have clearly identified common polymorphism affecting BMI and obesity. We undertook a genotype study to examine the impact of variants, known to influence obesity, in a sample from the Saudi Arabian population, notable for its profound combination of low mean physical activity indices and high energy intake. Anthropometry measures and genotypes were obtained for 367 Saudis, taken from King Saud University and Biomarker Screening Project in Riyadh (Riyadh Cohort). We observed large effect sizes with obesity for rs10767664 (BDNF) (OR = 1.923, ) and rs3751812 (FTO) (OR = 1.523, ) in our sample and, using weighted genetic risk scores, we found strong evidence of a cumulative effect using 11 SNPs taken predominantly from loci principally affecting appetite (OR = 2.57, ). We used conditional analyses to discern which of our three highly correlated FTO SNPs were responsible for the observed signal, although we were unable to determine with confidence which best marked the causal site. Our analysis indicates that markers located in loci known to influence fat mass through increased appetite affect obesity in Saudi Arabians to an extent possibly greater than in Europeans. Larger scale studies will be necessary to obtain a precise comparison. Khalid K. Alharbi, Tom G. Richardson, Imran Ali Khan, Rabbani Syed, Abdul Khader Mohammed, Christopher R. Boustred, Tom R. Gaunt, Waleed Tamimi, Nasser M. Al-Daghri, and Ian N. M. Day Copyright © 2014 Khalid K. Alharbi et al. All rights reserved. Systemic Oxidative Stress Biomarkers in Chronic Periodontitis: A Meta-Analysis Sun, 16 Nov 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/931083/ Oxidative stress biomarkers have been observed in peripheral blood of chronic periodontitis patients; however, their associations with periodontitis were not consistent. This meta-analysis was performed to clarify the associations between chronic periodontitis and oxidative biomarkers in systemic circulation. Electronic searches of PubMed and Embase databases were performed until October 2014 and articles were selected to meet inclusion criteria. Data of oxidative biomarkers levels in peripheral blood of periodontitis patients and periodontal healthy controls were extracted to calculate standardized mean differences (SMDs) and 95% confidence intervals (CIs) by using random-effects model. Of 31 eligible articles, 16 articles with available data were included in meta-analysis. Our results showed that periodontitis patients had significantly lower levels of total antioxidant capacity (SMD = −2.02; 95% CI: −3.08, −0.96; ) and higher levels of malondialdehyde (SMD = 0.99; 95% CI: 0.12, 1.86; ) and nitric oxide (SMD = 4.98; 95% CI: 2.33, 7.63; ) than periodontal healthy control. Superoxide dismutase levels between two groups were not significantly different (SMD = −1.72; 95% CI: −3.50, 0.07; ). In conclusion, our meta-analysis showed that chronic periodontitis is significantly associated with circulating levels of three oxidative stress biomarkers, indicating a role of chronic periodontitis in systemic diseases. Zhiqiang Liu, Yan Liu, Yiqing Song, Xi Zhang, Songlin Wang, and Zuomin Wang Copyright © 2014 Zhiqiang Liu et al. All rights reserved. Preoperative Serum Levels of Mesothelin in Patients with Colon Cancer Thu, 13 Nov 2014 08:33:06 +0000 http://www.hindawi.com/journals/dm/2014/161954/ Background. Screening for biochemical markers is important for diagnosing colon cancer. In this study, the reliability of serum mesothelin levels as a potential diagnostic and screening instrument was evaluated concerning colon cancer. Methods. Ninety-five patients who had undergone colonoscopic examination and who were diagnosed with colon cancer were included in the study. The serum mesothelin levels were measured with the ELISA kits and were evaluated in terms of significant difference when compared between colon cancer and control group. Results. Patients with colon cancer had significantly higher mesothelin serum levels than the control groups. We found significant associations between serum levels and tumor grade, perineural invasion, and vascular invasion (resp., ). Conclusion. Evaluating the serum levels of mesothelin has a potential to detect and screen the colon cancer in affected patients. Our data suggest that mesothelin exhibits effects towards colon cancer and serves as a biomarker for this deadly disease. Özgür Bostancı, Özgür Kemik, Ahu Kemik, Muharrem Battal, Uygar Demir, Sevim Purisa, Alpaslan Yavuz, and Mehmet Mihmanlı Copyright © 2014 Özgür Bostancı et al. All rights reserved. Prognostic and Biological Significance of MicroRNA-127 Expression in Human Breast Cancer Wed, 12 Nov 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/401986/ The purpose of this study was to determine the expression of miR-127 and analyze its prognostic and biological significance in breast cancer (BC). A quantitative reverse transcription PCR assay was performed to detect the expression of miR-127 in 15 pairs of BC and corresponding noncancerous tissues. The expression of miR-127 was detected in another 110 BC tissues and its correlations with clinicopathological factors of patients were examined. Univariate and multivariate analyses were performed to analyze the prognostic significance of miR-127 expression. The effects of miR-127 expression on malignant phenotypes of BC cells and its possible molecular mechanisms were further determined. miR-127 was significantly downregulated in BC tissues, and low miR-127 expression was significantly correlated with lymph node metastasis and advanced clinical stage. Patients with low miR-127 showed poorer overall survival than those with high miR-127. Multivariate analyses indicated that status of miR-127 was an independent prognostic factor for patients. Functional analyses showed that upregulation of miR-127 significantly inhibited growth, enhanced apoptosis, and reduced migration and invasion in BC cells by targeting the protooncogene BCL-6. Therefore, miR-127 may be a potential biomarker for predicting the survival of BC patients and might be a molecular target for treatment of human BCs. Shaohua Wang, Hanjun Li, Jingjie Wang, Dan Wang, Anlong Yao, and Qiurong Li Copyright © 2014 Shaohua Wang et al. All rights reserved. The CCR5Δ32 Polymorphism in Brazilian Patients with Sickle Cell Disease Tue, 11 Nov 2014 11:54:50 +0000 http://www.hindawi.com/journals/dm/2014/678246/ Background. Previous studies on the role of inflammation in the pathophysiology of sickle cell disease (SCD) suggested that the CCR5Δ32 allele, which is responsible for the production of truncated C-C chemokine receptor type 5 (CCR5), could confer a selective advantage on patients with SCD because it leads to a less efficient Th1 response. We determined the frequency of the CCR5Δ32 polymorphism in 795 Afro-Brazilian SCD patients followed up at the Pernambuco Hematology and Hemotherapy Center, in Northeastern Brazil, divided into a pediatric group (3 months–17 years, ) and an adult group (18–70 years, ). The adult patients were also compared to a healthy control group (blood donors, 18–61 years, ). Methods. The CCR5/CCR5Δ32 polymorphism was determined by allele-specific PCR. Results. No homozygous patient for the CCR5Δ32 allele was detected. The frequency of heterozygotes in the study population (patients and controls) was 5.8%, in the total SCD patients 5.1%, in the children 5.4%, in the adults with SCD 4.8%, and in the adult controls 8.1%. These differences did not reach statistical significance. Conclusions. Our findings failed to demonstrate an important role of the CCR5Δ32 allele in the population sample studied here. Mariana Pezzute Lopes, Magnun Nueldo Nunes Santos, Eliel Wagner Faber, Marcos André Cavalcanti Bezerra, Betânia Lucena Domingues Hatzlhofer, Dulcinéia Martins Albuquerque, Tânia Regina Zaccariotto, Daniela Maria Ribeiro, Aderson da Silva Araújo, Fernando Ferreira Costa, and Maria de Fátima Sonati Copyright © 2014 Mariana Pezzute Lopes et al. All rights reserved. The Clinicopathologic Importance of Serum Lactic Dehydrogenase in Patients with Gastric Cancer Tue, 04 Nov 2014 08:24:55 +0000 http://www.hindawi.com/journals/dm/2014/140913/ Background. To explore possible correlation between serum lactate dehydrogenase (SLDH) levels and gastric cancer. Materials and Methods. We retrospectively reviewed 365 patients with gastric cancer. The correlation of SLDH levels with clinicopathologic features and survival rate was studied. Results. SLDH levels were closely associated with the pathological (p) T stage (), metastasis (), pTNM stage (), and recurrence (). Moreover, we found a significant SLDH level difference among Borrmann type (), pT stage (), lymph node metastasis (), metastasis (), pTNM stage (), and recurrence (). In addition, we detected a significant SLDH level difference between alive and dead subgroups (). In addition, both univariate analysis and multivariate analysis showed that high SLDH levels were independent prognostic factor. For the subgroup with normal LDH (median point of 157.0 U/L), we detected that the subset with SLDH levels ≥157 U/L (158–245 U/L) showed poorer OS () and DFS () than that of ≤157 subgroup. Conclusions. Our results suggest that high SLDH level could be an independent poor prognostic biomarker. Gastric cancer patients with relative high SLDH level (158–245 U/L) were prone to develop a shorter OS and DFS. Zhi Zhao, Fanghai Han, Shibin Yang, Lixin Hua, Jianhai Wu, and Wenhua Zhan Copyright © 2014 Zhi Zhao et al. All rights reserved. A Disease Modification Effect of APOE E4 on the Association between Urinary Albumin Excretion and Cognition in Korean Adults Thu, 30 Oct 2014 08:49:41 +0000 http://www.hindawi.com/journals/dm/2014/724281/ Background. No previous study examined a disease modifying effect of APOE E4 status on the association between the urinary albumin-to-creatinine ratio (UACR) and cognition. This study aimed to investigate whether APOE E4 modified the association in Korean adults. Methods. We performed a cross-sectional study in adults aged 45 to 74 who were living in Namwon City, Republic of Korea. Cognitive function was measured with the Korean version of modified Mini-Mental State Examination (K-mMMSE) and cognitive impairment was defined as scores falling below the 25th percentile of the K-mMMSE according to age, sex, and educational attainments. Results. A total of 10,190 participants (4006 men and 6184 women) were analyzed in the present study. Of these, 1698 subjects (16.7%) were APOE E4 carriers. The UACR values were negatively associated with the K-mMMSE scores, even after adjusting for potential confounders including age, sex, education, and vascular risk factors. APOE E4 modified the association significantly, resulting in a steeper decline of cognitive function with the increase in UACR in E4 carriers (P for interaction = 0.021). Conclusion. Higher UACR values were significantly associated with cognitive dysfunction in the general Korean population, with cognition in APOE E4 carriers being more severely affected by increased UACR. Min-Ho Shin, Sun-Seog Kweon, Jin-Su Choi, Young-Hoon Lee, Hae-Sung Nam, Kyeong-Soo Park, Hee Nam Kim, Sun-Young Oh, and Seul-Ki Jeong Copyright © 2014 Min-Ho Shin et al. All rights reserved. Functional Polymorphisms of Matrix Metalloproteinases 1 and 9 Genes in Women with Spontaneous Preterm Birth Tue, 28 Oct 2014 06:33:26 +0000 http://www.hindawi.com/journals/dm/2014/171036/ Objective. The aim of this study was to investigate the association of functional MMP-1-1607 1G/2G and MMP-9-1562 C/T gene polymorphisms with spontaneous preterm birth (SPTB; preterm birth with intact membranes) in European Caucasian women, as well as the contribution of these polymorphisms to different clinical features of women with SPTB. Methods and Patients. A case-control study was conducted in 113 women with SPTB and 119 women with term delivery (control group). Genotyping of MMP-1-1607 1G/2G and MMP-9-1562 C/T gene polymorphisms was performed using the combination of polymerase chain reaction and restriction fragment length polymorphism methods. Results. There were no statistically significant differences in the distribution of neither individual nor combinations of genotype and allele frequencies of MMP-1-1607 1G/2G and MMP-9-1562 C/T polymorphisms between women with SPTB and control women. Additionally, these polymorphisms do not contribute to any of the clinical characteristics of women with SPTB, including positive and negative family history of SPTB, gestational age at delivery, and maternal age at delivery, nor fetal birth weight. Conclusion. We did not find the evidence to support the association of MMP-1-1607 1G/2G and MMP-9-1562 C/T gene polymorphisms with SPTB in European Caucasian women. Nina Pereza, Ivana Pleša, Ana Peterlin, Žiga Jan, Nataša Tul, Miljenko Kapović, Saša Ostojić, and Borut Peterlin Copyright © 2014 Nina Pereza et al. All rights reserved. Prognostic Significance of MicroRNA-375 Downregulation in Solid Tumors: A Meta-Analysis Thu, 23 Oct 2014 07:56:36 +0000 http://www.hindawi.com/journals/dm/2014/626185/ Objective. Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may play an important role as prognostic biomarker of cancers. We performed a meta-analysis to evaluate the impact of miR-375 expression in solid tumors on patients’ overall survival (OS). Methods. Studies were identified by searching PubMed, Embace, and Cochrane Library (last search update was in May 2014) and were assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and stratified analyses were calculated to investigate the association between miR-375 expression and cancer patients OS. Results. Our analysis results indicated that downregulation of miR-375 predicted poor OS (HR = 1.91, 95% CI 1.48–2.45, ). Subgroup analyses showed that lower expression of miR-375 was significantly related with poor OS in patients with esophageal carcinoma (HR = 2.24, 95% CI 1.69–2.96, ) and non-small-cell lung cancer (NSCLC) (HR = 1.71, 95% CI 1.31–2.24, ). Conclusions. The findings from this meta-analysis suggest that miR-375 expression is associated with OS of patients with malignant tumors and could be a useful clinical prognostic biomarker. Yingjie Shao, Yiting Geng, Wendong Gu, Jin Huang, Zhonghua Ning, and Honglei Pei Copyright © 2014 Yingjie Shao et al. All rights reserved. MicroRNA-21 Promotes Cell Growth and Migration by Targeting Programmed Cell Death 4 Gene in Kazakh’s Esophageal Squamous Cell Carcinoma Tue, 21 Oct 2014 12:02:18 +0000 http://www.hindawi.com/journals/dm/2014/232837/ Esophageal cancer (EC) is the eighth most common cancer worldwide and the sixth most common cause of cancer death. There are two main types of EC—squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). Although some advances in the exploration of its possible etiological mechanism were made recently including behaviors and environmental risk factors as well as gene alterations, the molecular mechanism underlying ESCC carcinogenesis and progression remains poorly understood. It has been reported that miR-21 was upregulated in most malignant cancers, the proposed mechanism of which was through suppressing expression of programmed cell death 4 (PDCD4). In present study, it is firstly reported that miR-21 was upregulated in Kazakh’s ESCC and that miR-21 played a negative role in regulating PDCD4 using in situ hybridization (ISH) and luciferase reporter approach. Morever, in model of ESCC xenografted nude mice, miR-21 maybe used as an effective target in the treatment. The present results demonstrated that miR-21 may be a potential therapeutic target in management of ESCC. Tao Liu, Qing Liu, Shutao Zheng, Xiangpeng Gao, Mang Lu, Chenchen Yang, Fang Dai, Ilyar Sheyhidin, and Xiaomei Lu Copyright © 2014 Tao Liu et al. All rights reserved. The Association between Bile Salt Export Pump Single-Nucleotide Polymorphisms and Primary Biliary Cirrhosis Susceptibility and Ursodeoxycholic Acid Response Sun, 19 Oct 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/350690/ Background. Primary biliary cirrhosis (PBC) is a chronic and progressive cholestasis liver disease. Bile salt export pump (BSEP) is the predominant bile salt efflux system of hepatocytes. BSEP gene has been attached great importance in the susceptibility of PBC and the response rate of ursodeoxycholic acid (UDCA) treatment of PBC patients. Methods. In this study, TaqMan assay was used to genotype four variants of BSEP, and the Barcelona criteria were used for evaluating the response rate of UDCA treatment. Results. Variant A allele of BSEP rs473351 (dominant model, OR = 2.063; 95% CI, 1.254–3.393; ) was highly associated with PBC susceptibility. On the contrary, variant A allele of BSEP rs2287618 (dominant model, OR = 0.617; 95% CI, 0.411–0.928; ) provided a protective role and Barcelona evaluation criterion indicated that the frequency of variant allele at BSEP rs2287618 was significantly decreased in UDCA-responsive PBC patients (). Conclusion. These results suggested that BSEP rs473351 was closely associated with the susceptibility of PBC and if people with BSEP rs2287618 were diagnosed as PBC, the UDCA treatment was not satisfactory. Larger studies with mixed ethnicity subjects and stratified by clinical and subclinical characteristics are needed to validate our findings. Rui-rui Chen, Yuan-jun Li, Xin-min Zhou, Lu Wang, Juan Xing, Shuang Han, Li-na Cui, Lin-hua Zheng, Kai-chun Wu, Yong-quan Shi, Zhe-yi Han, Ying Han, and Dai-ming Fan Copyright © 2014 Rui-rui Chen et al. All rights reserved. Prediabetes Is Associated with HNF-4α P2 Promoter Polymorphism rs1884613: A Case-Control Study in Han Chinese Population and an Updated Meta-Analysis Wed, 15 Oct 2014 11:28:55 +0000 http://www.hindawi.com/journals/dm/2014/231736/ Background. Controversy remains for the association between hepatocyte nuclear factor 4α (HNF-4α) P2 promoter polymorphism rs1884613 and type 2 diabetes (T2D). There was no association test of this polymorphism with prediabetes and T2D in the Chinese population. Moreover, an updated meta-analysis in various ethnic groups is needed to establish the contribution of rs1884613 to T2D risk. Methods. Using the Sequenom MassARRAY platform approach, we genotyped rs1884613 of HNF-4α in the P2 promoter region among 490 T2D patients, 471 individuals with prediabetes, and 575 healthy controls. All the individuals were recruited from 16 community health service centers in Nanshan district in Shenzhen province. Using STATA 11.0 software, meta-analysis was performed to summarize the overall contribution of rs1884613 to T2D risk. Results. Polymorphism rs1884613 was associated with genetic susceptibility to prediabetes in the whole samples (OR = 1.40, 95% CI = 1.16–1.68, ) and the female subgrouped samples (OR = 1.48, 95% CI = 1.14–1.92, ) after adjusting for age and body mass index (BMI). In contrast, there was no association of rs1884613 with T2D in the whole samples and male in our case-control study and meta-analysis. Conclusions. Our results suggest that rs1884613 contributes to susceptibility to prediabetes, whereas this polymorphism may not play an important role in the development of T2D. Changyi Wang, Sihan Chen, Tao Zhang, Zhongwei Chen, Shengyuan Liu, Xiaolin Peng, Jianping Ma, Xiaohong Zhong, Yanqiong Yan, Linlin Tang, Yifeng Mai, Liyuan Han, and Shiwei Duan Copyright © 2014 Changyi Wang et al. All rights reserved.