Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Diagnostic and Prognostic Markers in Bladder Cancer Thu, 29 Sep 2016 14:07:15 +0000 http://www.hindawi.com/journals/dm/2016/2425091/ Ja Hyeon Ku, Wun-Jae Kim, Seth P. Lerner, Felix Chun, and Luis Alex Kluth Copyright © 2016 Ja Hyeon Ku et al. All rights reserved. miR-1 Inhibits Cell Growth, Migration, and Invasion by Targeting VEGFA in Osteosarcoma Cells Thu, 29 Sep 2016 06:12:56 +0000 http://www.hindawi.com/journals/dm/2016/7068986/ microRNAs (miRNAs) are small noncoding RNAs and have been shown to play a crucial role in the osteosarcoma (OS) tumorigenesis and progression. VEGFA is a key regulator of angiogenesis and plays an important role in regulation of tumor metastasis. The objective of this study was to determine whether VEGFA was involved in miR-1-mediated suppression of proliferation, migration, and invasion of OS cells. The expression levels of miR-1 were significantly lower in OS tumor tissues than those in adjacent normal tissues and in SAOS-2 and U2OS cell lines compared to a normal osteoblast (NHOst) cell line. VEGFA was upregulated in OS tumor tissues and SAOS-2 and U2OS cell lines. The results of CCK-8 assay and transwell assay showed that miR-1 acted as a tumor suppressor by inhibiting cell proliferation, migration, and invasion in U2OS cells. Dual luciferase reporter assay demonstrated that VEGFA was a direct and functional target gene of miR-1. miR-1 directly inhibits the protein expression of VEGFA via its 3′-UTR. Knockdown of VEGFA by siRNA inhibited proliferation, migration, and invasion of U2OS cells. Our study suggested the potential inhibitory function of miR-1 in OS cell proliferation, migration, and invasion via inhibiting VEGFA. Junjie Niu, Yibao Sun, Qiaoge Guo, Dongju Niu, and Bo Liu Copyright © 2016 Junjie Niu et al. All rights reserved. Is GERD a Factor in Osteonecrosis of the Jaw? Evidence of Pathology Linked to G6PD Deficiency and Sulfomucins Wed, 28 Sep 2016 13:39:35 +0000 http://www.hindawi.com/journals/dm/2016/8376979/ Osteonecrosis of the jaw (ONJ), a rare side effect of bisphosphonate therapy, is a debilitating disorder with a poorly understood etiology. FDA’s Adverse Event Reporting System (FAERS) provides the opportunity to investigate this disease. Our goals were to analyze FAERS data to discover possible relationships between ONJ and specific conditions and drugs and then to consult the scientific literature to deduce biological explanations. Our methodology revealed a very strong association between gastroesophageal reflux and bisphosphonate-induced ONJ, suggesting acidosis as a key factor. Overgrowth of acidophilic species, particularly Streptococcus mutans, in the oral microbiome in the context of insufficient acid buffering due to impaired salivary glands maintains the low pH that sustains damage to the mucosa. Significant associations between ONJ and adrenal insufficiency, vitamin C deficiency, and Sjögren’s syndrome were found. Glucose 6 phosphate dehydrogenase (G6PD) deficiency can explain much of the pathology. An inability to maintain vitamin C and other antioxidants in the reduced form leads to vascular oxidative damage and impaired adrenal function. Thus, pathogen-induced acidosis, hypoxia, and insufficient antioxidant defenses together induce ONJ. G6PD deficiency and adrenal insufficiency are underlying factors. Impaired supply of adrenal-derived sulfated sterols such as DHEA sulfate may drive the disease process. Stephanie Seneff, Nancy L. Swanson, Gerald Koenig, and Chen Li Copyright © 2016 Stephanie Seneff et al. All rights reserved. KIF2A Overexpression and Its Association with Clinicopathologic Characteristics and Poor Prognoses in Patients with Gastric Cancer Wed, 28 Sep 2016 09:41:24 +0000 http://www.hindawi.com/journals/dm/2016/7484516/ Kinesin family protein 2A (KIF2A), an M-type nonmotile microtubule depolymerase, has attracted attention for its role in carcinogenesis and poor prognoses in various human cancers. In this study, we aimed to evaluate the expression of KIF2A and its robustness and potential to predict clinical outcomes in gastric cancer (GC) patients. The messenger RNA (mRNA) expression of KIF2A was determined in 24 pairs of cancerous and adjacent nontumor tissues by real-time polymerase chain reaction. Immunohistochemistry of KIF2A was performed on a tissue microarray composed of 461 GC and 65 matched adjacent nontumor tissues removed during surgeries and 18 chronic gastritis, 15 intestinal metaplasia, and 37 low-grade and 62 high-grade intraepithelial neoplasias acquired through gastric endoscopic biopsies. Univariate and multivariate Cox regression models were used to perform survival analyses. The high KIF2A expression was significantly correlated to histological type, TNM stage, and lymph node metastasis. A negative correlation was found between KIF2A expression and the 5-year survival rate of GC patients. In addition, multivariate analysis indicated that KIF2A is an independent prognostic factor in GC. This study demonstrated the high KIF2A expression might serve as an independent marker for poor prognoses in GC patients. Shu Zhang, Fang Huang, Yan Wang, Qinjie Song, Xiaobing Yang, and Han Wu Copyright © 2016 Shu Zhang et al. All rights reserved. Dynamics of SOX2 and CDX2 Expression in Barrett’s Mucosa Tue, 27 Sep 2016 12:13:28 +0000 http://www.hindawi.com/journals/dm/2016/1532791/ Barrett’s esophagus (BE) is the replacement of the normal esophageal squamous epithelium by a columnar lining epithelium. It is a premalignant condition for the development of adenocarcinoma of the esophagus and esophagogastric junction. BE is associated with gastroesophageal reflux which might change the expression profile of key transcription factors involved in the establishment of tissue differentiation, namely, SOX2 (associated with esophageal and gastric differentiation) and CDX2 (associated with intestinal differentiation). Here, we sought to characterize the expression profile of SOX2 and CDX2 in the sequential alterations of the esophageal mucosa towards adenocarcinoma and compare it with the well-established gastric and intestinal mucin profiles (MUC5AC, MUC6, and MUC2). We observed that SOX2 and CDX2 expression correlates with gastric and intestinal differentiation in BE, defined by morphological parameters and mucin expression. We show the presence of a complete intestinal profile in BE, without gastric mucins and without SOX2, and we observed an evolutionary modulation of the metaplastic phenotype by SOX2 and CDX2. We observed that adenocarcinomas harbor more frequently a mixed gastric and intestinal phenotype. In conclusion, our study establishes a role for transcription factors SOX2 and CDX2 in the progression from gastric to gastrointestinal differentiation in Barrett’s metaplasia. Rita Barros, Daniela Pereira, Catarina Callé, Vânia Camilo, Ana Isabel Cunha, Leonor David, Raquel Almeida, António Dias-Pereira, and Paula Chaves Copyright © 2016 Rita Barros et al. All rights reserved. Quantitative and Qualitative Analysis of Circulating Cell-Free DNA Can Be Used as an Adjuvant Tool for Prostate Cancer Screening: A Meta-Analysis Tue, 27 Sep 2016 11:50:16 +0000 http://www.hindawi.com/journals/dm/2016/3825819/ As part of “liquid biopsy,” lots of literature indicated the potential diagnostic value of circulating cell-free DNA (cfDNA) in the management of prostate cancer (PCa). However, the literature on the accuracy of cfDNA detection in PCa has been inconsistent. Hence, we performed this meta-analysis to assess the diagnostic value of cfDNA in PCa. A total of 19 articles were included in this analysis according to the inclusion and exclusion criteria. We then investigated two main subgroups in this meta-analysis, including qualitative analysis of abnormal level of cfDNA and qualitative analysis of single-gene methylation alterations. Overall, the results of quantitative analysis showed sensitivity of 0.73 (95% CI, 0.62–0.82) and specificity of 0.80 (95% CI, 0.70–0.87), with an area under the curve (AUC) of 0.83 (95% CI, 0.80–0.86). For qualitative assessment, the values were 0.34 (95% CI, 0.22–0.48), 0.99 (95% CI, 0.97–1.00), and 0.91 (95% CI, 0.88–0.93), respectively. Our results suggest the pooled specificity of each subgroup is much higher than the specificity of prostate-specific antigen (PSA). However, they are not recommended for PCa screening alone, because their sensitivities are not higher than the conventional serum biomarkers PSA. We conclude that analysis of cfDNA can be used as an adjuvant tool for PCa screening. Changqing Yin, Changliang Luo, Wei Hu, Xu Ding, Chunhui Yuan, and Fubing Wang Copyright © 2016 Changqing Yin et al. All rights reserved. Cytokine Profile in Chronic Periodontitis Patients with and without Obesity: A Systematic Review and Meta-Analysis Mon, 26 Sep 2016 09:27:08 +0000 http://www.hindawi.com/journals/dm/2016/4801418/ To investigate the cytokine profile as biomarkers in the gingival crevicular fluid (GCF) of chronic periodontitis (CP) patients with and without obesity, MEDLINE/PubMed, EMBASE, ScienceDirect, and SCOPUS databases were combined with handsearching of articles published from 1977 up to May 2016 using relevant MeSH terms. Meta-analyses were conducted separately for each of the cytokines: resistin, adiponectin, TNF-α, leptin, IL-6, IL-8, and IL-1β. Forest plots were produced reporting standardized mean difference of outcomes and 95% confidence intervals. Eleven studies were included. Three studies showed comparable levels of leptin among obese and nonobese patients with CP. Four studies reported comparable levels of interleukin- (IL-) 6 and resistin whereas five studies reported comparable levels of adiponectin. Two studies reported similar levels of CRP in patients with periodontitis with and without obesity. One study showed higher levels of tumor necrosis factor-alpha in obese patients with CP. One study showed higher levels of IL-1β and IL-8 in obese patients with CP. The level of localized periodontal inflammation may have a greater influence on the GCF proinflammatory biomarker levels as compared to systemic obesity. Whether patients having chronic periodontitis with obesity have elevated proinflammatory GCF biomarkers levels compared to nonobese individuals remains debatable. Zohaib Akram, Tariq Abduljabbar, Mohamed Ibrahim Abu Hassan, Fawad Javed, and Fahim Vohra Copyright © 2016 Zohaib Akram et al. All rights reserved. Pathway Analysis Based on Attractor and Cross Talk in Colon Cancer Sun, 25 Sep 2016 13:04:09 +0000 http://www.hindawi.com/journals/dm/2016/2619828/ Colon cancer is the third and second most common cancer form in men and women worldwide. It is generally accepted that colon cancer mainly results from diet. The aim of this study was to identify core pathways which elucidated the molecular mechanisms in colon cancer. The microarray data of E-GEOD-44861 was downloaded from ArrayExpress database. All human pathways were obtained from Kyoto Encyclopedia of Genes and Genomes database. In total, 135 differential expressed genes (DEG) were identified using Linear Models for Microarray Data package. Differential pathways were identified with the method of attractor after overlapping with DEG. Pathway cross talk network (PCN) was constructed by combining protein-protein interactions and differential pathways. Cross talks of all pathways were obtained in PCN. There were 65 pathways with RankProd (RP) values < 0.05 and 16 pathways with Impact Factors (IF) values > 100. Five pathways were satisfied with value < 0.05, RP values < 0.05, and IF values > 100, which were considered to be the most important pathways in colon cancer. In conclusion, the five pathways were identified in the center status of colon cancer, which may contribute to understanding the mechanism and development of colon cancer. Yanxia Liu, Lin Wang, Bingping Wang, Meng Yue, and Yufeng Cheng Copyright © 2016 Yanxia Liu et al. All rights reserved. The Effect of Poly(ADP-ribose) Polymerase-1 Gene 3′Untranslated Region Polymorphism in Colorectal Cancer Risk among Saudi Cohort Sun, 25 Sep 2016 12:13:58 +0000 http://www.hindawi.com/journals/dm/2016/8289293/ Background. DNA repair systems are essential for each cell to repair and maintain the genome integrity. Base excision repair pathway is one of the crucial pathways to maintain genome integrity and PARP-1 plays a key role in BER pathway. The purpose of this study is to evaluate the association between polymorphisms in PARP-1 3′untranslated region (3′UTR) SNP rs8679 and its expression in colorectal cancer. Methods. Genotyping and gene expression were performed using TaqMan assays. The effects of age, gender, and tumor location were evaluated in cases and controls regarding the genotyping results. Resulting data was analyzed using SPSS software. Results and Conclusions. Genotyping analysis for SNP rs8679 showed decreased susceptibility to colorectal cancer at heterozygous TC allele and at minor allele C. Further this protective association was also observed in younger age patients (≤57), in female patients, and also in patients with tumors located at colon and rectum. PARP-1 expression levels are significantly different in colorectal cancer compared to matched normal tissue. Our findings proved that the upregulation of PARP-1 is associated with tumor progression and poor prognosis in Saudi patients with colorectal cancer, suggesting that PARP-1 can be novel and valuable signatures for predicting the clinical outcome of patients with colorectal cancer. Abdullah M. Alhadheq, Jilani Purusottapatnam Shaik, Abdullah Alamri, Abdulrahman M. Aljebreen, Othman Alharbi, Majid A. Almadi, Faten Alhadeq, Nahla A. Azzam, Abdelhabib Semlali, Mohammad Alanazi, Mohammad D. Bazzi, and Narasimha Reddy Parine Copyright © 2016 Abdullah M. Alhadheq et al. All rights reserved. Concentration and Methylation of Cell-Free DNA from Blood Plasma as Diagnostic Markers of Renal Cancer Tue, 20 Sep 2016 10:29:46 +0000 http://www.hindawi.com/journals/dm/2016/3693096/ The critical point for successful treatment of cancer is diagnosis at early stages of tumor development. Cancer cell-specific methylated DNA has been found in the blood of cancer patients, indicating that cell-free DNA (cfDNA) circulating in the blood is a convenient tumor-associated DNA marker. Therefore methylated cfDNA can be used as a minimally invasive diagnostic marker. We analysed the concentration of plasma cfDNA and methylation of six tumor suppressor genes in samples of 27 patients with renal cancer and 15 healthy donors as controls. The cfDNA concentrations in samples from cancer patients and healthy donors was measured using two different methods, the SYBR Green I fluorescence test and quantitative real-time PCR. Both methods revealed a statistically significant increase of cfDNA concentrations in cancer patients. Hypermethylation on cfDNA was detected for the LRRC3B (74.1%), APC (51.9%), FHIT (55.6%), and RASSF1 (62.9%) genes in patients with renal cancer. Promoter methylation of VHL and ITGA9 genes was not found on cfDNA. Our results confirmed that the cfDNA level and methylation of CpG islands of RASSF1A, FHIT, and APC genes in blood plasma can be used as noninvasive diagnostic markers of cancer. Inessa Skrypkina, Liudmyla Tsyba, Kateryna Onyshchenko, Dmytro Morderer, Olena Kashparova, Oleksii Nikolaienko, Grigory Panasenko, Sergii Vozianov, Alina Romanenko, and Alla Rynditch Copyright © 2016 Inessa Skrypkina et al. All rights reserved. Identification of Differentially Expressed Kinase and Screening Potential Anticancer Drugs in Papillary Thyroid Carcinoma Thu, 15 Sep 2016 07:56:35 +0000 http://www.hindawi.com/journals/dm/2016/2832980/ Aim. We aim to identify protein kinases involved in the pathophysiology of papillary thyroid carcinoma (PTC) in order to provide potential therapeutic targets for kinase inhibitors and unfold possible molecular mechanisms. Materials and Methods. The gene expression profile of GSE27155 was analyzed to identify differentially expressed genes and mapped onto human protein kinases database. Correlation of kinases with PTC was addressed by systematic literature search, GO and KEGG pathway analysis. Results. The functional enrichment analysis indicated that “mitogen-activated protein kinases pathway” expression was extremely enriched, followed by “neurotrophin signaling pathway,” “focal adhesion,” and “GnRH signaling pathway.” MAPK, SRC, PDGFRa, ErbB, and EGFR were significantly regulated to correct these pathways. Kinases investigated by the literature on carcinoma were considered to be potential novel molecular therapeutic target in PTC and application of corresponding kinase inhibitors could be possible therapeutic tool. Conclusion. SRC, MAPK, and EGFR were the most important differentially expressed kinases in PTC. Combined inhibitors may have high efficacy in PTC treatment by targeting these kinases. Huairong Zhang, Bo Gao, and Bingyin Shi Copyright © 2016 Huairong Zhang et al. All rights reserved. TBL1XR1 Is Highly Expressed in Gastric Cancer and Predicts Poor Prognosis Thu, 08 Sep 2016 07:02:13 +0000 http://www.hindawi.com/journals/dm/2016/2436518/ Objective. To investigate the expression of transducin- (β-) like 1 X-linked receptor 1 (TBL1XR1) in human gastric cancer (GC) and its correlation with prognostic and biologic significance. Methods. TBL1XR1 mRNA expression was analyzed in gastric cancer using a microarray dataset (GSE2701) from the Gene Expression Omnibus (GEO). Immunohistochemistry (IHC) analysis of TBL1XR1 was performed on GC tissue microarray (TMA) to assess its prognostic and biological significance in 334 patients of GC. Results. Analysis of GSE2701 showed that the mRNA levels of TBL1XR1 were significantly elevated in primary gastric tumor and lymph node tissues than normal gastric tissues (). The same results of TBL1XR1 protein level were observed by IHC staining in 334 GC tissues. 204 of 334 (60.1%) primary gastric cancer tissues showed high expression of TBL1XR1 protein. TBL1XR1 overexpression was significantly correlated with lymph node metastasis () and advanced TNM stage (). Moreover, high levels of TBL1XR1 predicted worse overall survival (). Multivariate Cox regression analysis indicated that high expression of TBL1XR1 was an independent prognostic factor for poor overall survival (HR, 0.525; 95% confidence interval, 0.367–0.752; ). Conclusion. This present study demonstrates that TBL1XR1 is overexpressed in gastric cancer and may be a potential predictor and therapeutic target for GC patients. Fang Liu, Yuan He, Qinghua Cao, Ni Liu, and Wenhui Zhang Copyright © 2016 Fang Liu et al. All rights reserved. Increased Serum Level of MicroRNA-663 Is Correlated with Poor Prognosis of Patients with Nasopharyngeal Carcinoma Wed, 07 Sep 2016 16:48:35 +0000 http://www.hindawi.com/journals/dm/2016/7648215/ MicroRNAs (miRs) play crucial roles in the carcinogenesis and malignant progression of human cancers including nasopharyngeal carcinoma (NPC). In this study, we aimed to investigate the association of serum miR-663 levels with the clinical factors and prognosis of NPC patients. Real-time PCR was performed to examine the amount of miR-663 in serum in NPC patients and healthy controls. Our data showed that the amount of miR-663 in serum was significantly higher in NPC patients than in healthy controls. Moreover, the serum levels of miR-663 were significantly correlated with the grade, lymph node metastasis, and clinical stage of NPC. Furthermore, higher serum miR-663 levels were closely associated with worse 5-year overall survival (OS) and relapse-free survival (RFS) of patients with NPC, and the serum level of miR-663 was found to be an independent predicator for the prognosis of NPC. In addition, after receiving chemoradiotherapy, the serum levels of miR-663 were significantly reduced in NPC patients. In summary, miR-663 was upregulated in the serum of NPC patients, which was downregulated after chemoradiotherapy, and its increased levels were closely associated with malignant progression and poor prognosis in NPC patients. Therefore, the amount of miR-663 in serum may become a potential predicator for the clinical outcome of NPC patients. Shaoqiang Liang, Ning Zhang, Yanming Deng, Lusi Chen, Yang Zhang, Zhenhe Zheng, Weijun Luo, Zhiqian Lv, Shaoen Li, and Tao Xun Copyright © 2016 Shaoqiang Liang et al. All rights reserved. Proteomic Biomarkers Panel: New Insights in Chronic Kidney Disease Wed, 07 Sep 2016 09:09:41 +0000 http://www.hindawi.com/journals/dm/2016/3185232/ Chronic kidney disease, despite being a “silent epidemic” disease, represents one of the main causes of mortality in general population, along with cardiovascular disease, which is the leading cause of poor prognosis for these patients. The specific objective of our study was to characterize the relationship between the inflammatory status, the bone disorders markers, and kidney failure in chronic kidney disease patient stages 2–4, in order to design a novel biomarker panel that improves early disease diagnosis and therapeutic response, thus being further integrated into clinical applications. A panel of proteomic biomarkers, assessed by xMAP array, which includes mediators of inflammation (IL-6, TNF-α) and mineral and bone disorder biomarkers (OPG, OPN, OCN, FGF-23, and Fetuin-A), was found to be more relevant than a single biomarker to detect early CKD stages. The association between inflammatory cytokines and bone disorders markers, IL-6, TNF-α, OPN, OPG, and FGF-23, reflects the severity of vascular changes in CKD and predicts disease progression. Proteomic xMAP analyses shed light on a new approach to clinical evaluation for CKD staging and prognosis. Simona Mihai, Elena Codrici, Ionela Daniela Popescu, Ana-Maria Enciu, Elena Rusu, Diana Zilisteanu, Radu Albulescu, Gabriela Anton, and Cristiana Tanase Copyright © 2016 Simona Mihai et al. All rights reserved. TaqI, FokI, and ApaI Polymorphisms in the Vitamin D Receptor in Behçet’s Disease in Turkish Population Thu, 01 Sep 2016 09:29:11 +0000 http://www.hindawi.com/journals/dm/2016/7475080/ Objectives. In our study we aimed to determine VDR gene polymorphisms in patients with Behçet’s disease (BD) and neuro-Behçet’s disease (NBD) in Turkish population. Methods. PBL obtained from 37 patients with BD, 21 patients with NB, and 30 healthy controls were investigated. Genomic DNA was extracted from whole blood using the QIAamp Blood Kit. VDR ApaI (rs7975232), VDR FokI (rs2228570), and VDR TaqI (rs731236) genotyping was performed by real-time polymerase chain reaction with SimpleProbe melting-curve analysis. Results. The allelic and genotype distributions of FokI and TaqI polymorphisms were not different among Behçet’s disease, neuro-Behçet’s disease, and control subjects in Turkish population (). Only the frequency of ApaI A allele in control is higher than that in BD (60% versus 38.5%), and the value is 0.014, but the power is not enough to conclude that ApaI A allele is protective in BD in our study. Taken together, we found no significant differences between the BD, NBD, and control groups regarding the distribution of ApaI, TaqI, and FokI genotype and alleles frequencies. Conclusions. Future studies with larger patients’ numbers may show differences between VDR polymorphisms and Behçet’s disease. Gaye Erten, Muhammed Kalkan, Sema Bilgiç Gazioğlu, Nilgun Akdeniz, Elif Ozkok, and Burcak Vural Copyright © 2016 Gaye Erten et al. All rights reserved. Multiplatform Biomarker Discovery for Bladder Cancer Recurrence Diagnosis Wed, 31 Aug 2016 08:30:23 +0000 http://www.hindawi.com/journals/dm/2016/4591910/ Purpose. Nonmuscle invasive bladder cancer (BCa) has a high recurrence rate requiring lifelong surveillance. Urinary biomarkers are promising as simple alternatives to cystoscopy for the diagnosis of recurrent bladder cancer. However, no single marker can achieve the required accuracy. The purpose of this study was to select a multiparameter panel, comprising urinary biomarkers and clinical parameters, for BCa recurrence diagnosis. Experimental Design. Candidate biomarkers were measured in urine samples of BCa patients with recurrence and BCa patients without recurrence. A multiplatform strategy was used for marker quantification comprising a multiplexed microarray and an automated platform for ELISA analysis. A multivariate statistical analysis combined the results from both platforms with the collected clinical data. Results. The best performing combination of biomarkers and clinical parameters achieved an AUC value of 0.91, showing better performance than individual parameters. This panel comprises six biomarkers (cadherin-1, IL-8, ErbB2, IL-6, EN2, and VEGF-A) and three clinical parameters (number of past recurrences, number of BCG therapies, and stage at time of diagnosis). Conclusions. The multiparameter panel could be a useful noninvasive tool for BCa surveillance and potentially impact the clinical management of this disease. Validation of results in an independent cohort is warranted. Marine De Paoli, Selma Gogalic, Ursula Sauer, Claudia Preininger, Hardev Pandha, Guy Simpson, Andras Horvath, and Christophe Marquette Copyright © 2016 Marine De Paoli et al. All rights reserved. Galactose-Deficient IgA1 as a Candidate Urinary Polypeptide Marker of IgA Nephropathy? Sun, 28 Aug 2016 14:48:24 +0000 http://www.hindawi.com/journals/dm/2016/7806438/ In patients with IgA nephropathy (IgAN), circulatory IgA1 and IgA1 in mesangial deposits contain elevated amounts of galactose-deficient IgA1 (Gd-IgA1). We hypothesized that a fraction of Gd-IgA1 from the glomerular deposits and/or circulation may be excreted into the urine and thus represent a disease-specific biomarker. Levels of urinary IgA and Gd-IgA1 were determined in 207 patients with IgAN, 205 patients with other renal diseases, and 57 healthy controls, recruited in USA, Japan, and Italy. Urinary IgA was similarly elevated in patients with IgAN and renal-disease controls compared with healthy controls. However, urinary Gd-IgA1 levels were higher in patients with IgAN (IgAN, ; disease controls, units/mg urinary creatinine; ). Lectin western blotting data confirmed these results. In IgAN patients, levels of urinary Gd-IgA1 correlated with proteinuria (). When we purified IgA from serum and urine of an IgAN patient, the relative proportion of Gd-IgA1 to total IgA1 was higher in the urine compared with serum, suggesting selective excretion of Gd-IgA1 in IgAN. In summary, urinary excretion of Gd-IgA1 was elevated in patients with IgAN and the urinary Gd-IgA1 levels correlated with proteinuria. Urinary Gd-IgA1 may thus represent a disease-specific biomarker of IgAN. Hitoshi Suzuki, Landino Allegri, Yusuke Suzuki, Stacy Hall, Zina Moldoveanu, Robert J. Wyatt, Jan Novak, and Bruce A. Julian Copyright © 2016 Hitoshi Suzuki et al. All rights reserved. Correlation of Serum β-Endorphin and the Quality of Life in Allergic Rhinitis Thu, 25 Aug 2016 16:13:48 +0000 http://www.hindawi.com/journals/dm/2016/2025418/ Background. Allergic rhinitis (AR) significantly impairs the quality of life of the patients; however, a questionnaire alone is an insufficient and subjective measure of this condition. Obtaining an objective clinical assessment of the level of impairment will be valuable for its treatment. β-Endorphin is one of the most important mediators of both mental state and specific immunity. Thus, we investigated the possibility of using β-endorphin as a biomarker for evaluating the impairment level in AR. Methods. This study included 48 patients with AR and 32 healthy volunteers. The serum β-endorphin level was determined by enzyme immunoassay, and the serum-specific IgE and total IgE levels were determined by immunoblot assay. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was used to assess the impairment level in the symptom duration. Results. The β-endorphin concentration was significantly decreased in AR patients compared to the healthy controls (, ). There was significant negative correlation between the impairment level and serum β-endorphin level (correlation coefficient: 0.468; ; ), but there was no association between the serum β-endorphin and total IgE levels (, ). Conclusion. -Endorphin is a systemic biomarker that has the potential to assess the impairment level in AR and may therefore be a novel therapeutic target for the treatment of AR. Jichao Sha, Cuida Meng, Lin Li, Na Cui, Qian Xiu, and Dongdong Zhu Copyright © 2016 Jichao Sha et al. All rights reserved. CEACAM1: Expression and Role in Melanocyte Transformation Wed, 24 Aug 2016 18:00:21 +0000 http://www.hindawi.com/journals/dm/2016/9406319/ Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination. Gabriela Turcu, Roxana Ioana Nedelcu, Daniela Adriana Ion, Alice Brînzea, Mirela Daniela Cioplea, Lucia Beatrice Jilaveanu, and Sabina Andrada Zurac Copyright © 2016 Gabriela Turcu et al. All rights reserved. The Role of Fecal Calprotectin in Evaluating Intestinal Involvement of Behçet’s Disease Wed, 24 Aug 2016 06:11:23 +0000 http://www.hindawi.com/journals/dm/2016/5423043/ One of the regions of involvement of Behçet’s disease (BD), a systematic inflammatory vasculitis with unknown etiology, is the gastrointestinal (GI) tract. Upper GI endoscopy, colonoscopy, and capsule endoscopy are frequently used methods to diagnose the intestinal involvement of BD. The aim of this study was to investigate the role of fecal calprotectin (FC) in the evaluation of intestinal involvement in BD. Material and Method. A total of 30 patients who were diagnosed with BD and had no GI symptoms and 25 individuals in the control group were included in this study. Results. Levels of FC were statistically significantly higher in patients with BD compared to the control group (). The correlation analysis performed including FC and markers of disease activity revealed a positive and statistically significant correlation between FC level and CRP and erythrocyte sedimentation rate (: 0.255, , and : 0.404, , resp.). FC levels in patients who were detected to have ulcers in the terminal ileum and colon in the colonoscopic examination were statistically significantly higher compared to the patients with BD without intestinal involvement (). Conclusion. The measurement of FC levels, in patients with BD who are asymptomatic for GI involvement, may be helpful to detect the possible underlying intestinal involvement. Burak Özşeker, Cem Şahin, Havva Solak Özşeker, S. Cumali Efe, Taylan Kav, and Yusuf Bayraktar Copyright © 2016 Burak Özşeker et al. All rights reserved. From Normal Skin to Squamous Cell Carcinoma: A Quest for Novel Biomarkers Tue, 23 Aug 2016 14:21:41 +0000 http://www.hindawi.com/journals/dm/2016/4517492/ Squamous cells carcinoma (SCC) is the second most frequent of the keratinocyte-derived malignancies after basal cell carcinoma and is associated with a significant psychosocial and economic burden for both the patient himself and society. Reported risk factors for the malignant transformation of keratinocytes and development of SCC include ultraviolet light exposure, followed by chronic scarring and inflammation, exposure to chemical compounds (arsenic, insecticides, and pesticides), and immune-suppression. Despite various available treatment methods and recent advances in noninvasive or minimal invasive diagnostic techniques, the risk recurrence and metastasis are far from being negligible, even in patients with negative histological margins and lymph nodes. Analyzing normal, dysplastic, and malignant keratinocyte proteome holds special promise for novel biomarker discovery in SCC that could be used in the future for early detection, risk assessment, tumor monitoring, and development of targeted therapeutic strategies. Vlad Voiculescu, Bogdan Calenic, Mihaela Ghita, Mihai Lupu, Ana Caruntu, Liliana Moraru, Suzana Voiculescu, Alexandra Ion, Maria Greabu, Nikolay Ishkitiev, and Constantin Caruntu Copyright © 2016 Vlad Voiculescu et al. All rights reserved. miR-155 Inhibits Nucleus Pulposus Cells’ Degeneration through Targeting ERK 1/2 Thu, 18 Aug 2016 08:30:47 +0000 http://www.hindawi.com/journals/dm/2016/6984270/ We first investigated the difference in microRNA expression between normal NP cells and degenerative NP cells using gene chip. We have found that the expression of ERK1/2 was decreased with overexpression of miR-155 in normal nucleus pulposus cell. Expression of ERK1/2 was increased with inhibition of miR-155. Overexpression or inhibition of miR-155 had no effects on the expression level of mRNA ERK1/2 in nucleus pulposus cell, which showed that miR-155 affected the expression of pERK1/2 after transcription of ERK1/2 mRNA indicating that ERK1/2 was a new target protein regulated by miR-155. In the degeneration of intervertebral disc, inhibited miR-155 decreased the expressions of extracellular main matrix collagen II and glycosaminoglycan and increased expression of ERK1/2. Taken together, our data suggested that miR-155 was the identified miRNA which regulated NP cells degenerated through directly targeting ERK1/2. Dongping Ye, Libing Dai, Yicun Yao, Shengnan Qin, Han Xie, Wen Wang, and Weiguo Liang Copyright © 2016 Dongping Ye et al. All rights reserved. Detection of Soluble ED-A+ Fibronectin and Evaluation as Novel Serum Biomarker for Cardiac Tissue Remodeling Thu, 18 Aug 2016 07:44:00 +0000 http://www.hindawi.com/journals/dm/2016/3695454/ Background and Aims. Fibronectin containing the extra domain A (ED-A+ Fn) was proven to serve as a valuable biomarker for cardiac remodeling. The study was aimed at establishing an ELISA to determine ED-A+ Fn in serum of heart failure patients. Methods. ED-A+ Fn was quantified in serum samples from 114 heart failure patients due to ischemic (ICM, ) and dilated (DCM, ) cardiomyopathy as well as hypertensive heart disease (HHD, ) compared to healthy controls (). Results. In comparison to healthy volunteers, heart failure patients showed significantly increased levels of ED-A+ Fn (). In particular in ICM patients there were significant associations between ED-A+ Fn serum levels and clinical parameters, for example, increased levels with rising NYHA class (), a negative correlation with left ventricular ejection fraction (, : −0.353), a positive correlation with left atrial diameter (, : 0.431), and a strong positive correlation with systolic pulmonary artery pressure (, : 0.485). In multivariate analysis, ED-A+ Fn was identified as an independent predictor of an ischemic heart failure etiology. Conclusions. The current study could clearly show that ED-A+ Fn is a promising biomarker in cardiovascular diseases, especially in heart failure patients due to an ICM. We presented a valid ELISA method, which could be applied for further studies investigating the value of ED-A+ Fn. Barbara Ziffels, Johanna Ospel, Katja Grün, Dario Neri, Alexander Pfeil, Michael Fritzenwanger, Hans R. Figulla, Christian Jung, Alexander Berndt, and Marcus Franz Copyright © 2016 Barbara Ziffels et al. All rights reserved. Expression of Cancer Testis Antigens in Colorectal Cancer: New Prognostic and Therapeutic Implications Thu, 18 Aug 2016 06:44:05 +0000 http://www.hindawi.com/journals/dm/2016/1987505/ Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study. We selected a panel of 18 CTAs that were previously detected in CRC as well as some new gene candidates, and their expression was detected at the mRNA level by employing RQ-PCR. Additionally, we evaluated CTA expression in three colon cancer cell lines (CL-188, HTB-39, and HTB-37) after exposure to the DNA methylation-modifying drug 5-azacytidine. Results. We report that 6 out of 18 (33%) CTAs tested (MAGEA3, OIP5, TTK, PLU1, DKKL1, and FBXO39) were significantly () overexpressed in tumor tissue compared with healthy colon samples isolated from the same patients. Conclusions. Moreover, we found that MAGEA3, PLU-1, and DKKL expression positively correlated with disease progression, evaluated according to the Dukes staging system. Finally, 5-azacytidine exposure significantly upregulated expression of CTAs on CRC cells, which indicates that this demethylation agent could be employed therapeutically to enhance the immune response against tumor cells. Maciej Tarnowski, Michał Czerewaty, Anna Deskur, Krzysztof Safranow, Wojciech Marlicz, Elżbieta Urasińska, Mariusz Z. Ratajczak, and Teresa Starzyńska Copyright © 2016 Maciej Tarnowski et al. All rights reserved. Osteopontin in relation to Prognosis following Coronary Artery Bypass Graft Surgery Sun, 14 Aug 2016 11:53:35 +0000 http://www.hindawi.com/journals/dm/2016/1868739/ Cardiovascular events may occur even after complete revascularization in patients with coronary artery disease. We measured preoperative osteopontin (OPN) levels in 131 consecutive patients ( years old, 117 men and 14 women) with left ventricular ejection fraction of and low logistic EuroScore () undergoing elective Coronary Artery Bypass Grafting (CABG) surgery. Patients were prospectively followed up for a median of 12 months (range 11–24). The primary study endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, need for repeat revascularization, and hospitalization for cardiovascular events. Pre-op OPN plasma levels were 77.9 (49.5, 150.9). Patients with prior acute myocardial infarction (AMI) had significantly higher OPN levels compared to those without [131.5 (52.2, 219) versus 73.3 (45.1, 125), ]. OPN levels were positively related to EuroScore (, ). Pre-op OPN levels did not differ between patients who had a major adverse event during follow-up compared to those with no event () and had no effect on the hazard of future adverse cardiac events [HR (95% CI): 1.48 (0.43–4.99), ]. The history of AMI was associated with increased risk of subsequent cardiovascular events at follow-up (). OPN is associated with preoperative risk assessment prior to low-risk CABG but did not independently predict outcome. Eftihia Sbarouni, Panagiota Georgiadou, Sofia Chatzikyriakou, Antonis Analitis, Antigoni Chaidaroglou, Demitris Degiannis, and Vassilis Voudris Copyright © 2016 Eftihia Sbarouni et al. All rights reserved. Plasma Brain-Derived Neurotrophic Factor as a Biomarker for the Main Types of Mild Neurocognitive Disorders and Treatment Efficacy: A Preliminary Study Thu, 11 Aug 2016 13:15:49 +0000 http://www.hindawi.com/journals/dm/2016/4095723/ Decreased levels of brain-derived neurotrophic factor (BDNF) are assumed to play a crucial role in the pathophysiology of mild neurocognitive disorders (MNCDs). In this study, we compared plasma BDNF levels (at baseline and after two months of treatment with escitalopram) in patients with the main types of MNCDs and normal controls. 21 patients met the DSM-5 diagnostic criteria for possible MNCD due to Alzheimer’s disease (MNCD-AD); 22 patients fulfilled the diagnostic criteria for subcortical vascular MNCD (ScVMNCD) according to Frisoni et al. (2002) and neuroimaging-supported probable diagnosis of vascular MNCD according to DSM-5; 16 subjects entered control group. At baseline, we detected lower BDNF levels in both MNCD groups, which was significant only in subjects with MNCD-AD. Moreover, plasma BDNF level of 21160 pg/mL showed high sensitivity (94%) to discriminate patients with MNCD-AD. Decreased plasma BDNF highly correlated with the severity of memory impairment and total MMSE score in MNCD-AD group. Escitalopram treatment in patients with MNCD-AD or ScVMNCD led to an increase of plasma BDNF concentrations and as a result to a decrease of cognitive, depressive, and anxiety symptom severity. In conclusion, plasma BDNF might be a reliable biomarker for the validation of MNCD-AD diagnosis and treatment efficacy. Oleg A. Levada, Nataliya V. Cherednichenko, Andriy V. Trailin, and Alexandra S. Troyan Copyright © 2016 Oleg A. Levada et al. All rights reserved. GSTP1 Methylation and Protein Expression in Prostate Cancer: Diagnostic Implications Wed, 10 Aug 2016 13:23:49 +0000 http://www.hindawi.com/journals/dm/2016/4358292/ GSTP1 belongs to the GSTs family, a group of enzymes involved in detoxification of exogenous substances and it also plays an important role in cell cycle regulation. Its dysregulation correlates with a large variety of tumors, in particular with prostate cancer. We investigated GSTP1 methylation status with methylation specific PCR (MS-PCR) in prostate cancer (PCa) and in benign tissue of 56 prostatectomies. We also performed immunohistochemistry (IHC) so as to correlate gene methylation with gene silencing. GSTP1 appears methylated in PCa and not in healthy tissue; IHC confirmed that methylation leads to protein underexpression (). GSTP1 is highly expressed in basal cell layer and luminal cells in benign glands while in prostatic intraepithelial neoplasia (PIN) it stains only basal cell layer, whereas PCa glands are completely negative. We demonstrated that methylation leads to underexpression of GSTP1. The progressive loss of GSTP1 expression from healthy glands to PIN and to PCa glands underlines its involvement in early carcinogenesis. Filippo Martignano, Giorgia Gurioli, Samanta Salvi, Daniele Calistri, Matteo Costantini, Roberta Gunelli, Ugo De Giorgi, Flavia Foca, and Valentina Casadio Copyright © 2016 Filippo Martignano et al. All rights reserved. Oxidative Stress-Related Biomarkers in Postmenopausal Osteoporosis: A Systematic Review and Meta-Analyses Wed, 10 Aug 2016 11:45:51 +0000 http://www.hindawi.com/journals/dm/2016/7067984/ Numerous studies suggested that oxidative stress (OS) played a central role in the onset and development of postmenopausal osteoporosis (PO); however, conflicting results were obtained as to the association of OS-related biomarkers and PO. This meta-analysis aimed to identify the association between these markers and PO, and explore factors that may explain the inconsistencies in these results. A systematic literature search was conducted in relevant database. Search terms and selection criteria were priorly determined to identify and include all studies that detected markers of OS in PO patients. We pooled data with a random effects meta-analysis with standardized mean differences and 95% confidence interval. Total 17 studies including 12 OS markers were adopted. The results showed that superoxide dismutase (SOD) in erythrocytes, catalase (CAT), total antioxidant status (TAS), hydroperoxides (HY), advanced oxidation protein products (AOPP), malondialdehyde (MDA), and vitamin B12 (VB12) in plasma/serum were not statistically different between the PO and control group, whereas significantly increased level of homocysteine (Hcy) and nitric oxide (NO), along with decreased SOD, glutathione peroxidase (GPx), folate, and total antioxidant power (TAP) in plasma/serum were obtained in the PO group. In summary, OS might serve as potential biomarkers in the etiopathophysiology and clinical course of PO. Qiaozhen Zhou, Li Zhu, Dafeng Zhang, Ning Li, Qiao Li, Panpan Dai, Yixin Mao, Xumin Li, Jianfeng Ma, and Shengbin Huang Copyright © 2016 Qiaozhen Zhou et al. All rights reserved. New Progress of Epigenetic Biomarkers in Urological Cancer Tue, 09 Aug 2016 12:58:58 +0000 http://www.hindawi.com/journals/dm/2016/9864047/ Urological cancers consist of bladder, kidney, prostate, and testis cancers and they are generally silenced at their early stage, which leads to the loss of the best opportunity for early diagnosis and treatment. Desired biomarkers are scarce for urological cancers and current biomarkers are lack of specificity and sensitivity. Epigenetic alterations are characteristic of nearly all kinds of human malignances including DNA methylation, histone modification, and miRNA regulation. Besides, the detection of these epigenetic conditions is easily accessible especially for urine, best target for monitoring the diseases of urinary system. Here, we summarize some new progress about epigenetic biomarkers in urological cancers, hoping to provide new thoughts for the diagnosis, treatment, and prognosis of urological cancers. Peng Wu, Ziyi Cao, and Song Wu Copyright © 2016 Peng Wu et al. All rights reserved. Urinary Lysosomal Enzyme Activities and Albuminuria in Ghanaian Patients with Type 2 Diabetes Mellitus Tue, 09 Aug 2016 08:23:46 +0000 http://www.hindawi.com/journals/dm/2016/2810639/ Renal tubular lysosomal enzyme activities like alanine aminopeptidase (AAP) and N-acetyl--D-glucosaminidase (NAG) have been shown to increase in patients developing diabetic nephropathy and nephrosclerosis. This study aimed to determine the activities of N-acetyl--D-glucosaminidase and alanine aminopeptidase and albumin concentration in urine samples of patients with type 2 diabetes. One hundred and thirty (65 type 2 diabetic and 65 nondiabetic) subjects participated in this study. Blood samples were drawn for measurements of fasting blood glucose, albumin (Alb), lipids, and creatinine (Cr). Early morning spot urine samples were also collected for activities of alanine aminopeptidase (AAP), N-acetyl--D-glucosaminidase (NAG), and concentration of albumin (U-Alb) and creatinine (U-Cr). Both NAG/Cr and AAP/Cr were significantly increased in diabetic subjects compared to controls (). There was positive correlation between NAG/Cr and Alb/Cr (, ) and between NAG/Cr and serum creatinine (, ). A negative correlation was found between NAG/Cr and eGFR (, ). 9.3% and 12% of diabetics with normoalbuminuria had elevated levels of AAP/Cr and NAG/Cr, respectively. We conclude that measuring the urinary enzymes activities (NAG/Cr and AAP/Cr) could be useful as a biomarker of early renal involvement in diabetic complications. Henry Asare-Anane, Felix Twum, Emmanuel Kwaku Ofori, Erving L. Torgbor, Seth D. Amanquah, and Charlotte Osafo Copyright © 2016 Henry Asare-Anane et al. All rights reserved.