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The aim of this case-control study was to assess whether PPARG and IGF2BP2 polymorphisms confer susceptibility to esophageal squamous-cell carcinoma (ESCC). A total of 507 patients pathologically confirmed for ESCC and 1,496 age-, sex-, and residence-matched healthy individuals were enrolled. The PPARG rs1801282 C>G and rs3856806 C>T and IGF2BP2 rs1470579 A>C and rs4402960 G>T polymorphisms were selected and genotyped by SNPscan genotyping assays. Multivariable logistic analysis suggested that the PPARG rs3856806 C>T polymorphism might increase the risk of ESCC. In different stratified analyses, there were significant associations between PPARG rs3856806 C>T and risk of ESCC in female, never-smoking, drinking, and never-drinking subgroups. In addition, we also found that PPARG rs1801282 C>G increased ESCC risk in the never-smoking subgroup. There was significant difference in Crs1470579Grs4402960Crs1801282Crs3856806-haplotype distribution among ESCC cases and control subjects. In conclusion, our findings highlight that PPARG rs1801282 C>G and rs3856806 C>T polymorphisms are candidates for susceptibility to ESCC in the eastern Chinese Han population. The Crs1470579Grs4402960Crs1801282Crs3856806 haplotype is associated with susceptibility to ESCC.

// Yan Chen 1 , Zhenzhou Xiao 1 , Minhua Hu 1 , Xiaoli Luo 1 and Zhaolei Cui 1 1 Laboratory of Biochemistry and Molecular Biology Research, Fujian Provincial Key Laboratory of Tumor Biotherapy, Department of Clinical Laboratory, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China Correspondence to: Zhaolei Cui, email: cuileidizi@fjmu.edu.cn Keywords: MALAT-1, cancer, diagnosis, meta-analysis Received: June 19, 2017 Accepted: August 26, 2017 Published: September 18, 2017 ABSTRACT Metastasis-associated lung adenocarcinoma transcript 1 ( MALAT-1 ) is one kind of long non-coding RNAs (lncRNAs) that has been recognized as a hallmark of the onset and development of several carcinomas. This study seek to meta-analyze the overall diagnostic efficacy of elevated MALAT-1 expression profile for human cancers. Studies on the diagnostic performance of MALAT-1 in cancers were retrieved by searching the online databases. The combined effect sizes were summarized using a bivariate meta-analysis model. Impacts of publication bias on the pooled effect sizes were assessed using “Duval and Tweedie nonparametric trim and fill method”. Sensitivity analysis and meta-regression test were applied to deeply trace the heterogeneity sources among eligible studies. A total of 14 studies with 1342 cancer cases were included. The combined effect sizes showed that MALAT-1 expression profiling conferred an estimated sensitivity of 0.69 (95% CI: 0.62–0.75) ( I 2 = 84.01%, P < 0.001), specificity of 0.85 (95% CI: 0.79–0.90) ( I 2 = 87.95%, P < 0.001) and AUC (area under curve) of 0.83 in distinguishing cancer patients from noncancerous contrasts. Moreover, stratified analysis depending on cancer type manifested that elevated MALAT-1 harbored a promising efficacy in the diagnosis of pulmonary tumors (AUC = 0.90), digestive system tumors (AUC = 0.84), gynecologic cancers (AUC = 0.84) and nasopharyngeal carcinoma (AUC = 0.84), particularly in confirming the subtype of squamous carcinoma (AUC = 0.91) and non-small cell lung carcinoma (AUC = 0.88) in lung cancer. Other analyses based on test matrix and ethnicity also presented robust results. Collectively, elevated MALAT-1 could be developed as an auxiliary molecular marker to aid in cancer diagnosis.

Inflammation is one of the major risk factors for cancer. Here, we show that calcium/calmodulin-dependent protein kinase II gamma (CAMK2γ) in intestinal epithelial cells (IECs) modulates inflammatory signals and promotes colitis-associated cancer (CAC) in mice. We have identified CAMK2γ as a downstream target of colitis-induced WNT5A signaling. Furthermore, we have shown that CAMK2γ protects against intestine tissue injury by increasing IEC survival and proliferation. Calcium/calmodulin-dependent protein kinase II gamma knockout mice displayed reduced CAC. Furthermore, we used bone marrow transplantation to reveal that CAMK2γ in IECs, but not immune cells, was crucial for its effect on CAC. Consistently, transgenic over-expression of CAMK2γ in IECs accelerated CAC development. Mechanistically, CAMK2γ in IECs enhanced epithelial signal transducer and activator of transcription 3 (STAT3) activation to promote survival and proliferation of colonic epithelial cells during CAC development. These results thus identify a new molecular mechanism mediated by CAMK2γ in IECs during CAC development, thereby providing a potential new therapeutic target for CAC.

// Zhaolei Cui 1 , Yan Chen 1 , Zhenzhou Xiao 1 , Minhua Hu 1 , Yingying Lin 1 , Yansong Chen 1 , Yuhong Zheng 1 1 Department of Clinical Laboratory, Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Provincial Cancer Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian, China Correspondence to: Yan Chen, e-mail: yanc2015@163.com Keywords: lncRNA, gastric cancer, biomarker, diagnostic accuracy, meta-analysis Received: November 09, 2015 Accepted: March 10, 2016 Published: March 22, 2016 ABSTRACT Background: Long non-coding RNAs (lncRNAs) are highlighted as novel cancer biomarkers with great promise. Herein, we focused on summarizing the overall diagnostic performance of lncRNAs for gastric cancer (GC). Methods: Publications fulfilling the search criteria were selected from the online databases. Study quality was assessed according to the Quality Assessment for Studies of Diagnostic Accuracy (QUADAS) checklist. The summary receiver operator characteristic (SROC) curve was plotted using a bivariate meta-analysis model. Statistical analysis was performed based on the platforms of STATA 12.0 and Meta-Disc 1.4 software. Results: Fifteen studies with 1252 patients and 1283 matched controls were included. The pooled sensitivity and specificity for lncRNA expression profile in differentiating GC patients from cancer-free individuals were 0.68 (95%CI: 0.61-0.74) and 0.79 (95%CI: 0.72-0.84), respectively, corresponding to an area under curve (AUC) of 0.80. Moreover, the stratified analyses demonstrated that plasma-based lncRNA profiling harbored higher accuracy than that tissue-based assay (specificity: 0.80 versus 0.75; AUC: 0.84 versus 0.77). Conclusions: LncRNA profiling hallmarks a moderate diagnostic value in the management of GC and that lncRNA expression patterns may potentially be utilized as auxiliary biomarkers in confirming GC.

The aim of this case–control study was to assess whether PPARG and IGF2BP2 polymorphisms confer susceptibility to esophageal squamous-cell carcinoma (ESCC). A total of 507 patients pathologically confirmed for ESCC and 1,496 age-, sex-, and residence-matched healthy individuals were enrolled. The PPARG rs1801282 C>G and rs3856806 C>T and IGF2BP2 rs1470579 A>C and rs4402960 G>T polymorphisms were selected and genotyped by SNPscan genotyping assays. Multivariable logistic analysis suggested that the PPARG rs3856806 C>T polymorphism might increase the risk of ESCC. In different stratified analyses, there were significant associations between PPARG rs3856806 C>T and risk of ESCC in female, never-smoking, drinking, and never-drinking subgroups. In addition, we also found that PPARG rs1801282 C>G increased ESCC risk in the never-smoking subgroup. There was significant difference in Crs1470579Grs4402960Crs1801282Crs3856806-haplotype distribution among ESCC cases and control subjects. In conclusion, our findings highlight that PPARG rs1801282 C>G and rs3856806 C>T polymorphisms are candidates for susceptibility to ESCC in the eastern Chinese Han population. The Crs1470579Grs4402960Crs1801282Crs3856806 haplotype is associated with susceptibility to ESCC.

Aberrant expression of microRNA (miRNA) has been highlighted as a helpful indicator to aid in nasopharyngeal carcinoma (NPC) diagnosis. The present meta-analysis aimed to validate the efficacy of miRNA as potential biomarkers for NPC detection. Publication searches were conducted on the online PubMed and EMBASE databases from inception to June 2016. A bivariate meta-analysis was performed to generate the diagnostic parameters based on Meta-Disc 1.4 and Stata 12.0 programs. Sensitivity analysis and meta-regression tests were applied to trace heterogeneity sources among eligible studies. A total of six studies comprising 528 patients with NPC and 252 matched controls were enrolled. Results from the present meta-analysis demonstrated that miRNA testing achieved a pooled sensitivity of 0.78 [95% confidence interval (CI), 0.70-0.84] and specificity of 0.79 (95% CI, 0.73-0.84) in confirming NPC, corresponding to an area under the curve (AUC) value of 0.85. Additionally, the pooled diagnostic odds ratio was estimated to be 9.01 (95% CI, 5.62-14.44), along with a positive likelihood ratio of 2.81 (95% CI, 2.19-3.61) and negative likelihood ratio of 0.35 (95% CI, 0.28-0.44). Additionally, the stratified analyses revealed that paralleled testing of miRNA sustained a pooled accuracy superior compared with that of single miRNA testing (sensitivity, 0.88 vs. 0.70; specificity, 0.85 vs. 0.69; AUC, 0.95 vs. 0.75). Testing of miRNA harbors a moderate diagnostic efficacy and is acceptable as an auxiliary biomarker for NPC diagnosis.

Vertical sleeve gastrectomy (VSG) is one of the most commonly performed clinical bariatric surgeries used for the remission of obesity and diabetes. However, the precise molecular mechanism by which VSG exerts its beneficial effects remains elusive. We report that the membrane-bound G protein-coupled bile acid receptor, GPBAR-1 (also known as TGR5), is required to mediate the effects of anti-obesity, anti-hyperglycemia, and improvements of fatty liver of VSG in mice. In the absence of TGR5, the beneficial metabolic effects of VSG in mice are lost. Moreover, we found that the expression of TGR5 increased significantly after VSG, and VSG alters both BA levels and composition in mice, resulting in enhancement of TGR5 signaling in the ileum and brown adipose tissues, concomitant with improved glucose control and increased energy expenditure. Conclusion: Our study elucidates a novel underlying mechanism by which VSG achieves its postoperative therapeutic effects through enhanced TGR5 signaling. (Hepatology 2016;64:760-773)

Background: Epigenetic alterations of gene or DNA methylation have been highlighted as promising biomarkers for early cervical cancer screening. Herein, we evaluated the diagnostic performance of paired boxed gene 1 (PAX1) and sex determining region Y-box 1 (SOX1) methylation for cervical cancer detection. Methods: Eligible studies were retrieved by searching the electronic databases. Study quality was assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. The bivariate meta-analysis model was employed to plot the summary receiver operator characteristic (SROC) curve using Stata 12.0 software. Results: The pooled sensitivity of PAX1 methylation was estimated to be 0.73 [95% confidence interval (CI): 0.70–0.75] in differentiating patients with HSIL (high-grade squamous intraepithelial lesion) or CIN3+ (cervical intraepithelial neoplasia type III/worse) or cervical cancer from normal individuals, corresponding to a specificity of 0.87 (95% CI: 0.85–0.89) and area under the curve (AUC) of 0.91. The SOX1 methylation test yielded an AUC of 0.82, under which, the pooled sensitivity was 0.71 (95% CI: 0.67–0.74) and specificity was 0.64 (95% CI: 0.61–0.67). Notably, the stratified analysis suggested that combing parallel testing of PAX1 methylation and human papillomavirus (HPV) DNA (AUC, sensitivity, and specificity of 0.89, 0.75, and 0.81, respectively) achieved higher accuracy than single HPV DNA testing (AUC, sensitivity, and specificity of 0.77, 0.81, and 0.70, respectively). Conclusions: PAX1 or SOX1 methylation has a prospect to be an auxiliary biomarker for cervical cancer screening, and parallel testing of PAX1 methylation and HPV DNA in cervical swabs confers an improved diagnostic accuracy than single HPV DNA testing.