This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity.We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters.Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016).E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD.
Abstract. Programmed death ligand-1 (PD-L1) is a potentially important tumor immunotherapy target. However, whether PD-L1 expression is associated with survival in nasopharyngeal carcinoma (NPC) remains controversial. The aim of the present study was to investigate the association between PD-L1 expression and prognosis in NPC. The expression of PD-L1 was assessed in tumor specimens from 120 patients with NPC using immunohistochemistry. Staining was evaluated using the H-score method. The associations between PD-L1 expression and clinical characteristics and prognosis were analyzed. Overall, 78% of the patients had stage I-III and 22% had stage IV disease. The estimated 5-year overall survival (OS) and disease-free survival (DFS) rates for the entire cohort were 87.5 and 70.1%, respectively. PD-L1 expression was detected in 85 (71%) patients and was localized to the tumor cells. High tumor expression of PD-L1 (median H-score ≥5) was associated with significantly poorer OS (P=0.023) and DFS (P=0.002). Univariate analysis indicated that low PD-L1 expression was associated with better DFS compared with high PD-L1 expression (HR=0.163, 95% CI: 0.044-0.600, P=0.006 for DFS). Multivariate analysis revealed that T stage (HR=8.190, P=0.023) and PD-L1 expression level (HR=0.124, 95% CI: 0.031-0.509; P=0.001) served as independent prognostic factors for DFS. In conclusion, tumor PD-L1 expression was found to be a significant prognostic factor in NPC, and high PD-L1 expression may be of prognostic value for recurrence and metastasis following conventional treatments.
Recent evidences show that genetic polymorphisms falling in miRNA binding sites can alter the strength of miRNA binding and disturb miRNA-mediated posttranscriptional regulation. Our study aimed to investigate the role of single-nucleotide polymorphisms (SNPs) in putative miRNA binding sites in gastric cancer (GC). Based on microarray and quantitative reverse transcription PCR analyses, we found that miR-181a was significantly upregulated in GC tissues. Bioinformatics survey was used to explore SNPs within miR-181a binding sites. Three SNPs were genotyped in a case-control study (500 cases and 502 controls). The T allele genotypes (rs12537CT and TT) of MTMR3 were found associated with significantly increased GC risk [adjusted odds ratio 1.72, 95% confidence interval (CI) 1.36-2.16, P = 3.99×10(-5)] and poor overall survival [hazard ratio (HR) 1.38, 95% CI 1.03-1.83, P = 0.029], although they were not an independent prognostic factor in multivariate Cox regression analysis (HR 1.28, 95% CI 0.95-1.72, P = 0.11). We further demonstrated that the rs12537CT genotype carriers had lower MTMR3 mRNA expression levels than CC genotype carriers in GC tissues (P = 0.013), whereas no significant difference in miR-181a expression levels was found (P = 0.135). Luciferase assay revealed that miR-181a directly targeted MTMR3, and its suppressive effect was enhanced when the rs12537C allele was substituted by T variant, although the difference was not significant (P = 0.055). Our study suggested that rs12537 is associated with susceptibility and prognosis of GC in southern Han Chinese, and miR-181a and its target gene MTMR3 play important roles in GC.
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