Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . 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. Hepatocyte Growth Factor Levels in the Saliva and Gingival Crevicular Fluid in Smokers with Periodontitis Wed, 15 Oct 2014 08:25:48 +0000 http://www.hindawi.com/journals/dm/2014/146974/ Hepatocyte growth factor (HGF) production by oral fibroblasts is enhanced by various molecules that are induced during inflammatory conditions including periodontitis. HGF plays an important role in the progression of periodontitis, by stimulating intense growth of epithelial cells and preventing regeneration of connective tissue attachments. Smokers have a greater risk factor in the pathogenesis and progression of periodontal disease. The objective of the study was to estimate the level of HGF in saliva and gingival crevicular fluid (GCF) in smokers with periodontitis and to compare these levels with that of nonsmokers with periodontitis and healthy controls. The HGF levels were found to be significantly high in the saliva and GCF of smokers with periodontitis compared to both never-smokers with periodontitis and the healthy control group. The elevated levels of HGF in the saliva and GCF in the study population could explain the intrinsic mechanism triggering the severity of the periodontitis in smokers. Further studies are necessary to validate the current observations and to establish a sensitive marker to predict periodontal disease activity. Sukumaran Anil, Sajith Vellappally, R. S. Preethanath, Sameer A. Mokeem, Hani S. AlMoharib, Shankargouda Patil, Elna P. Chalisserry, and Abdulaziz A. Al Kheraif Copyright © 2014 Sukumaran Anil et al. All rights reserved. Can Serum Glypican-3 Be a Biomarker for Effective Diagnosis of Hepatocellular Carcinoma? A Meta-Analysis of the Literature Tue, 14 Oct 2014 12:43:01 +0000 http://www.hindawi.com/journals/dm/2014/127831/ Objective. This review is to evaluate the diagnostic value of serum GPC3 for hepatocellular carcinoma (HCC) due to conflicting results reported. Methods. NCBI PubMed and Embase were comprehensively searched for studies that have used serum GPC3 level as a diagnostic index for HCC. The quality of the included studies was assessed. Subgroup analyses were conducted to evaluate the sensitivity and specificity of GPC3 as a HCC marker. Statistical analysis was performed with the software STATA version 12.0. Results. A total of 22 studies were included. The qualities of included studies were relatively poor. Among them, 18 studies have shown that serum GPC3 is a specific biomarker for HCC, and the pooled sensitivity and specificity of these studies were 69 and 93%, respectively. The other 4 studies have reported conflicting results, which were not caused by races, infection status of HBV and HCV, or assay reagents but due to one common experimental design of enrolling liver cirrhosis patients as control subjects. Conclusions. This meta-analysis indicates that serum GPC3 is elevated in HCC patients compared with healthy individuals, but more studies are needed to evaluate its effectiveness to differentially diagnose HCC and liver cirrhosis. Sheng-Li Yang, Xiefan Fang, Zao-Zao Huang, Xiang-Jie Liu, Zhi-Fan Xiong, Ping Liu, Hong-Yi Yao, and Chang-Hai Li Copyright © 2014 Sheng-Li Yang et al. All rights reserved. Prognostic Value of Rab27B Nuclear Expression in Gastrointestinal Stromal Tumors Tue, 14 Oct 2014 07:10:08 +0000 http://www.hindawi.com/journals/dm/2014/942181/ Rab proteins of the endocytosis and exocytosis pathways both play critical roles in cancer progression, and Rab27B has a significant relationship with several types of human cancer. However, the association between Rab27B expression and clinical features to determine its clinicopathological significance in gastrointestinal tumor (GIST) has not been investigated. To examine the expression of Rab27B in GIST and investigate the association between its expression and patient prognosis, immunohistochemistry analysis with tissue microarray was used to evaluate expression of Rab27B in 162 patients with GIST. The relationship between Rab27B expression and patient prognosis was analyzed. High nuclear staining of Rab27B was detected in 88 of 162 (54.32%) GIST tissues. Positive staining of Rab27B was significantly associated with tumor size (), mitotic index (), Armed Forces Institute of Pathology Miettinen risk classification (), and tumor grade (). Kaplan-Meier survival curves showed that GIST patients with low Rab27B nuclear expression () and mitotic index <5 per 50 high-power fields () had a more favorable prognosis. These findings indicate that Rab27B nuclear expression is correlated with several clinicopathological features of GIST patients, and it may serve as an unfavorable prognostic marker. Wei Wang, Qichao Ni, Hua Wang, Shu Zhang, and Huijun Zhu Copyright © 2014 Wei Wang et al. All rights reserved. Individually Tailored Screening of Susceptibility to Sarcopenia Using p53 Codon 72 Polymorphism, Phenotypes, and Conventional Risk Factors Mon, 13 Oct 2014 13:20:26 +0000 http://www.hindawi.com/journals/dm/2014/743634/ Background and Aim. p53 activity plays a role in muscle homeostasis and skeletal muscle differentiation; all pathways that lead to sarcopenia are related to p53 activities. We investigate the allelic frequency of the TP53 codon 72 in exon 4 polymorphism in the Italian female population and the association with appendicular skeletal muscle mass index in normal weight (NW), normal weight obese (NWO), and preobese-obese (Preob-Ob) subjects. Methods. We evaluated anthropometry, body composition, and p53 polymorphism in 140 women distinguished in NW, NWO, and Preob-Ob. Results. (RR = 0,31, 95% CI = 0,15–0,66, P = 0,0079). We developed a model able to predict sarcopenia risk based on age, body fat, and p53 polymorphism. Conclusion. Our study evidences that genotyping TP53 polymorphism could be a useful new genetic approach, in association with body composition evaluations, to assess sarcopenia risk. Laura Di Renzo, Santo Gratteri, Francesca Sarlo, Andrea Cabibbo, Carmen Colica, and Antonino De Lorenzo Copyright © 2014 Laura Di Renzo et al. All rights reserved. Importance of Follow-Up Cerebrospinal Fluid Analysis in Cryptococcal Meningoencephalitis Mon, 13 Oct 2014 12:07:39 +0000 http://www.hindawi.com/journals/dm/2014/162576/ Cryptococcal meningoencephalitis represents a serious infection of the central nervous system, where reliable prognostic factors during the disease course are needed. Twenty-one patients diagnosed with cryptococcal meningoencephalitis in a German university hospital from 1999 to 2013 were analysed retrospectively. CSF parameters were analysed prior to therapy and during antifungal treatment and were compared between patients who survived or deceased. Fifteen patients clinically improved after antifungal therapy, while six patients died. No differences were observed between the outcome groups for the CSF parameters cell count, lactate, total protein, and CSF-serum albumin quotients (QAlb). Follow-up examinations of serum cryptococcal antigen titer and CSF cell count have shown that these parameters cannot be used to monitor the efficacy of antifungal therapy as well. In contrast, the course of QAlb during therapy was indicative for the outcome as a possible prognostic marker. In patients with clinical improvement QAlb values were falling under therapy, while rising QAlb values were found in patients with fatal outcome indicating a continuing dysfunction of the blood-CSF barrier. In conclusion, our results indicate that, among the various CSF parameters, the course of QAlb presents a promising marker that might be used to monitor the efficacy of antifungal therapy. Thomas Skripuletz, Philipp Schwenkenbecher, Kaweh Pars, Matthias Stoll, Josef Conzen, Seza Bolat, Refik Pul, Ralf-Peter Vonberg, Ludwig Sedlacek, Ulrich Wurster, Martin Stangel, and Corinna Trebst Copyright © 2014 Thomas Skripuletz et al. All rights reserved. Elevated Plasma Stromal-Cell-Derived Factor-1 Protein Levels Correlate with Severity in Patients with Community-Acquired Pneumonia Mon, 13 Oct 2014 09:21:48 +0000 http://www.hindawi.com/journals/dm/2014/829706/ Background. The aim of this study was to investigate differential changes in plasma levels of stromal-cell-derived factor-1 (SDF-1) before and after antibiotic treatment in patients with community-acquired pneumonia (CAP) and observe the association between the severity of CAP and the plasma SDF-1 level. Methods. We gathered blood specimens from 61 adult CAP patients before and after antibiotic treatment and from 60 healthy controls to measure the plasma concentrations of SDF-1 by using an enzyme-linked immunosorbent assay. Results. The plasma SDF-1 concentration was elevated significantly in patients with CAP before receiving treatment compared with the controls and decreased significantly after the patients received treatment. Leukocyte (WBC) and neutrophil counts and C-reactive protein (CRP) levels decreased significantly after antibiotic treatment. Moreover, differences in the plasma concentration of SDF-1 were significantly correlated with PSI, CURB-65, and APACHE II scores (, , and ; , , and ; and , , and , resp.). Conclusions. An elevated plasma SDF-1 concentration can be used as a biological marker for the early diagnosis of CAP and for the early detection of its severity. Ping-Kun Tsai, Ming-Ju Hsieh, Hsiang-Ling Wang, Ming-Chih Chou, Shun-Fa Yang, and Chao-Bin Yeh Copyright © 2014 Ping-Kun Tsai et al. All rights reserved. System Accuracy Evaluation of the GlucoRx Nexus Voice TD-4280 Blood Glucose Monitoring System Mon, 13 Oct 2014 07:30:26 +0000 http://www.hindawi.com/journals/dm/2014/602586/ Use of blood glucose (BG) meters in the self-monitoring of blood glucose (SMBG) significantly lowers the risk of diabetic complications. With several BG meters now commercially available, the International Organization for Standardization (ISO) ensures that each BG meter conforms to a set degree of accuracy. Although adherence to ISO guidelines is a prerequisite for commercialization in Europe, several BG meters claim to meet the ISO guidelines yet fail to do so on internal validation. We conducted a study to determine whether the accuracy of the GlucoRx Nexus TD-4280 meter, utilized by our department for its cost-effectiveness, complied with ISO guidelines. 105 patients requiring laboratory blood glucose analysis were randomly selected and reference measurements were determined by the UniCel DxC 800 clinical system. Overall the BG meter failed to adhere to the ≥95% accuracy criterion required by both the 15197:2003 (overall accuracy 92.4%) and 15197:2013 protocol (overall accuracy 86.7%). Inaccurate meters have an inherent risk of over- and/or underestimating the true BG concentration, thereby risking patients to incorrect therapeutic interventions. Our study demonstrates the importance of internally validating the accuracy of BG meters to ensure that its accuracy is accepted by standardized guidelines. Muhammad Khan, Keith Broadbent, Mike Morris, David Ewins, and Franklin Joseph Copyright © 2014 Muhammad Khan et al. All rights reserved. A Comparison of KL-6 and Clara Cell Protein as Markers for Predicting Bronchopulmonary Dysplasia in Preterm Infants Wed, 27 Aug 2014 11:53:19 +0000 http://www.hindawi.com/journals/dm/2014/736536/ Objectives. To evaluate the predictive characteristics of KL-6 and CC16 for bronchopulmonary dysplasia (BPD) in preterm infants, either independently or in combination. Study Design. This prospective cohort study was performed from 2011 to 2013 with preterm neonates of gestational age ≤32 weeks and birth weight ≤1500 g. Serum KL-6 and CC16 levels were determined 7 and 14 days after birth. Results. Seventy-three preterm infants were studied. BPD was identified in 24 of these infants. After adjusting for potential confounders, serum KL-6 concentrations were found to be elevated in BPD infants at both time points relative to non-BPD infants, while serum CC16 concentrations were lower at 14 days. At both 7 d and 14 d of life the predictive power of KL-6 levels exceeded that of CC16 (area under receiver operating characteristic curve: at 7 d, 0.91 cf. 0.73, ; at 14 d, 0.95 cf. 0.85, ). The combination of these markers enhanced the sensitivity further. Conclusions. Serum KL-6 levels higher than 79.26 ng/mL at 14 days postpartum in preterm infants predict the occurrence of BPD. CC16 was less predictive than KL-6 at this time point, but KL-6 and CC16 together enhanced the prediction. Keyi Wang, Xianmei Huang, Hui Lu, and Zhiqun Zhang Copyright © 2014 Keyi Wang et al. All rights reserved. Two Polymorphisms in the Fractalkine Receptor CX3CR1 Gene Influence the Development of Atherosclerosis: A Meta-Analysis Tue, 26 Aug 2014 06:08:28 +0000 http://www.hindawi.com/journals/dm/2014/913678/ Background. The associations between the Fractalkine receptor (CX3CR1) gene T280M (rs3732378) and V249I (rs3732379) polymorphisms and atherosclerosis (AS) risk are conflicting. The aim of this meta-analysis was undertaken to assess their associations. Methods. PubMed, Embase, Web of Science, Medline, Cochrane database, and CNKI were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0. Results. Twenty-five articles involving 49 studies were included in the final meta-analysis. The analysis showed that the 280M allele carriers of the CX3CR1 T280M polymorphism decreased the risk of AS and coronary artery disease (CAD) in the heterozygous state but increased the risk of ischemic cerebrovascular disease (ICVD) in the homozygote state. The 249I allele carriers of the CX3CR1 V249I polymorphism decreased the risk of AS and CAD in the heterozygous state. The V249I-T280M combined genotype VITM and IITM also decreased the risk of AS. Conclusions. The present meta-analysis suggests that the CX3CR1 T280M and V249I polymorphisms are associated with the susceptibility to AS. However, the results should be interpreted with caution because of the high heterogeneity in the meta-analysis. Jian Wu, Rui-Xing Yin, Quan-Zhen Lin, Tao Guo, Guang-Yuan Shi, Jia-Qi Sun, Shao-Wen Shen, and Qing Li Copyright © 2014 Jian Wu et al. All rights reserved. Lead Exposure: A Summary of Global Studies and the Need for New Studies from Saudi Arabia Tue, 19 Aug 2014 06:09:49 +0000 http://www.hindawi.com/journals/dm/2014/415160/ Lead poisoning (plumbism) can cause irreversible genetic and reproductive toxicity, hematological effects, neurological damage, and cardiovascular effects. Despite many efforts to minimize lead poisoning, it continues to be a major health concern in many developing and developed countries. Despite efforts to control lead exposure and toxicity, serious cases of lead poisoning increasingly occur as a result of higher vehicular traffic and industrialization. The biomarkers for identification of genetic susceptibility to a particular disease are useful to identify individuals who are at risk for lead poisoning. Although many such studies have been taken up elsewhere, very few studies were performed in Saudi Arabia to assess susceptibility to lead poisoning. This indicates an urgent need for testing of susceptible individuals. The present paper was planned to understand the genetic susceptibility to lead toxicity in the various population studies conducted worldwide and also to correlate it with the current scenario in Saudi Arabia. Such studies are necessary for appropriate precautions in terms of diet and avoiding exposure to be used in order to prevent adverse health effects. A. P. Shaik, S. A. Sultana, and A. H. Alsaeed Copyright © 2014 A. P. Shaik et al. All rights reserved. Association of the Three Common SNPs of Cyclooxygenase-2 Gene (rs20417, rs689466, and rs5275) with the Susceptibility of Breast Cancer: An Updated Meta-Analysis Involving 34,590 Subjects Mon, 18 Aug 2014 06:29:16 +0000 http://www.hindawi.com/journals/dm/2014/484729/ Several single nucleotide polymorphisms have been identified in cyclooxygenase-2 (COX-2) genes (e.g., −765 G>C (rs20417), −1195G>A (rs689466), and 8473 C>T (rs5275)). The association of these SNPs with the risk of different cancer types is still controversial. This study aims to evaluate the correlation between these SNPs and breast cancer risk in different ethnic groups. We have searched PubMed, Web of Knowledge, and Embase for relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the associations. A total of 13 studies (15,330 cases and 19,260 controls) were eligible for meta-analysis. This meta-analysis showed that COX-2 rs20417 polymorphism was correlated with an increased risk of breast cancer in Caucasians, while rs689466 was associated with a decreased risk of breast cancer in Caucasians. The rs5275 polymorphism had no association with breast cancer risk. Zhi-Jun Dai, Yong-Ping Shao, Xiao-Bin Ma, Dan Xu, Wei Tang, Hua-Feng Kang, Shuai Lin, Meng Wang, Hong-Tao Ren, and Xi-Jing Wang Copyright © 2014 Zhi-Jun Dai et al. All rights reserved. The Serum Glycome to Discriminate between Early-Stage Epithelial Ovarian Cancer and Benign Ovarian Diseases Tue, 12 Aug 2014 09:37:11 +0000 http://www.hindawi.com/journals/dm/2014/238197/ Epithelial ovarian cancer (EOC) is the sixth most common cause of cancer deaths in women because the diagnosis occurs mostly when the disease is in its late-stage. Current diagnostic methods of EOC show only a moderate sensitivity, especially at an early-stage of the disease; hence, novel biomarkers are needed to improve the diagnosis. We recently reported that serum glycome modifications observed in late-stage EOC patients by MALDI-TOF-MS could be combined as a glycan score named GLYCOV that was calculated from the relative areas of the 11 N-glycan structures that were significantly modulated. Here, we evaluated the ability of GLYCOV to recognize early-stage EOC in a cohort of 73 individuals comprised of 20 early-stage primary serous EOC, 20 benign ovarian diseases (BOD), and 33 age-matched healthy controls. GLYCOV was able to recognize stage I EOC whereas CA125 values were statistically significant only for stage II EOC patients. In addition, GLYCOV was more sensitive and specific compared to CA125 in distinguishing early-stage EOC from BOD patients, which is of high relevance to clinicians as it is difficult for them to diagnose malignancy prior to operation. Karina Biskup, Elena Iona Braicu, Jalid Sehouli, Rudolf Tauber, and Véronique Blanchard Copyright © 2014 Karina Biskup et al. All rights reserved.