Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management

The prognostic value of GLUT1 in cancers: a systematic review and meta-analysis The prognostic value of GLUT1 in cancers: a systematic review and meta-analysis

Gut microbiota dysbiosis is closely associated with primary hepatocellular carcinoma (HCC). Recent studies have evaluated the early diagnosis of primary HCC through analysis of gut microbiota dysbiosis. However, the relationship between the degree of dysbiosis and the prognosis of primary HCC remains unclear. Because primary HCC is accompanied by dysbiosis and dysbiosis usually increases the circulatory concentrations of endotoxin and other harmful bacterial substances, which further increases liver damage, we hypothesized that level of dysbiosis associated with primary HCC increases with the stage of cancer progression. To test this hypothesis, we introduced a more integrated index referred to as the degree of dysbiosis (D_dys); and we investigated D_dys of the gut microbiota with the development of primary HCC through high-throughput sequencing of 16S rRNA gene amplicons. Our results showed that compared with healthy individuals, patients with primary HCC showed increased pro-inflammatory bacteria in their fecal microbiota. The D_dys increased significantly in patients with primary HCC compared with that in healthy controls. Moreover, there was a tendency for the D_dys to increase with the development of primary HCC, although no significant difference was detected between different stages of primary HCC. Our findings provide important insights into the use of gut microbiota analysis during the treatment of primary HCC.

Objective: Tumor-associated macrophages (TAMs) deserve more focus because of its pivotal role in the development of solid tumors and they are related to poor outcomes of several tumors. However, the prognostic value of tumor-infiltrating TAMs in pancreatic cancer is still controversial. Experimental design: We conduct a meta-analysis of 1699 patients in 13 studies by reviewing the studies in which the authors evaluated the prognostic value of TAMs density in pancreatic cancer. These studies were searched from inception to November 2018. Hazard ratios (HR) with their corresponding 95% confidence intervals (95% CIs) were assessed to explore the prognostic significance of TAMs in pancreatic cancer. Besides, we also conducted a subgroup analysis and sensitivity analysis. Two reviewers independently abstracted data. Results: A total of 13 studies with 1699 patients were pooled in the analysis to evaluate prognostic value of TAMs in pancreatic cancer. The pooled HRs demonstrated CD68+ TAMs correlated with worse overall survival (OS) in pancreatic cancer patients (HR =1.41, 95% CI =1.05–1.90, random effects model, I^2,=82.5%, P=0.021). And high generalized M2-TAMs density was significantly associated with poor OS (HR =1.95, 95% CI =1.63–2.33, random effects model, I^2,=59.2%, P=0.000) and disease-free survival (HR =1.83, 95% CI =1.43–2.36, fixed effects model, I^2,=0.00%, P=0.000). Pooled analysis showed no significant correlation between elevated TAMs infiltration and lymph node metastasis, tumor stage, histological grade, sex, or tumor location. Conclusion: The density of TAMs has an impact on the overall survival of pancreatic cancer patients. M2-TAMs can be recognized as a prognostic indicator in pancreatic cancer, which may serve as a potential therapeutic target in the treatment of pancreatic cancer.

Background: N6-methyladenosine (m6A) is the most prevalent modification of mammalian RNA. Emerging evidence suggest that m6A has critical roles in multiple biological activities, but little is known about its roles in cancer pathogenesis. Herein, we report the expression profiles and prognostic relevance of twelve m6A-related genes in hepatocellular carcinoma (HCC) by analyzing four independent datasets. Materials and methods: RNA levels of twelve m6A-related genes were detected in samples of 162 HCC patients who underwent curative resection (the Guangdong General Hospital dataset). We additionally analyzed the expression profiles of m6A-related genes in The Cancer Genome Atlas liver HCC dataset and two Gene Expression Omnibus datasets (GSE14520, GSE63898). Prognostic value of genes was evaluated by Kaplan–Meier curves of overall survival (OS) with the log-rank test and multivariate Cox regression analysis. Gene set enrichment analysis (GSEA) was conducted to identify associated KEGG pathways. Results: Five genes (METTL3, YTHDF1, YTHDF2, YTHDF3, and EIF3) showed consistent upregulation in all four datasets. Abnormal expressions of either METTL3 or YTHDF1 but not the other ten genes were associated with OS. Protein expression of METTL3 and YTHDF1 were confirmed in HCC tissues by immunohistochemical staining. Multivariate Cox regression analysis confirmed the independent predictive value of both METTL3 and YTHDF1 on OS. We further divided patients into three groups based on the median expression values of METTL3 and YTHDF1. In all datasets, the low METTL3/low YTHDF1 group showed a consistent better prognosis than other groups. GSEA revealed that both METTL3 and YTHDF1 regulate HCC cell cycle, RNA splicing, DNA replication, base excision repair, and RNA degradation. Conclusion: Both METTL3 and YTHDF1 were upregulated in HCC, and they were independent poor prognostic factors. Combination of METTL3 and YTHDF1 can be regarded as the biological marker that reflect malignant degree and evaluate prognosis in HCC.