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.

Increased glycolysis is one of the hallmarks of cancer. The abnormal expression of glucose transporter 1 (GLUT1) was reported to be associated with resistance to current therapy and poor prognosis. Numerous studies have investigated the correlation between GLUT1 expression and prognosis in cancers, but the conclusions are still controversial. Here, we conducted a meta-analysis to explore the association between GLUT1 and survival in human cancers. PubMed, Springer, Medline, and Cochrane Library were searched carefully to identify eligible studies evaluating prognostic value of GLUT1 in cancers. Twenty-seven studies with 4079 patients were included in the present study. Our pooled results identified that increased expression of GLUT1 was associated with unfavorable overall survival (HR = 1.780, 95% CI = 1.574–.013, p < 0.001)) and poorer disease-free survival (HR = 1.95, 95% CI = 1.229–3.095, p = 0.003). Furthermore, overexpression of GLUT1 linked with poor differentiated tumors (RR = 1.380, 95% CI = 1.086–1.755, p = 0.009; I2 = 72.0%, p < 0.001), positive lymph node metastasis (RR = 1.395, 95% CI = 1.082–1.799, p = 0.010; I2 = 70.8%, p = 0.002) and larger tumor size (RR = 1.405, 95% CI = 1.231–1.603, p < 0.001; I2 = 37.3%, p = 0.093). This systematic review and meta-analysis indicated that the GLUT1 may serve as an ideal prognostic biomarker in various cancers.

Background Orderly G2/M transition in the cell cycle is controlled by the cyclin-dependent kinase 1/cyclin B (CDK1/CCNB) complex. We aimed to comprehensively investigate the roles of CDK1, CCNB1, and CCNB2 via multi-omics analysis and their relationships with immune infiltration in hepatocellular carcinoma (HCC). Material/Methods The transcriptional data and the epigenetic and genetic alterations of CDK1 , CCNB1 , and CCNB2 , as well as their impacts on prognosis in HCC patients, were identified using multiple databases. The correlations between expression of these genes and immune infiltration in HCC were then explored using the TIMER database. Results Overall, mRNA expression of CDK1 , CCNB1 , and CCNB2 was up-regulated in various tumor tissues including HCC. Higher expression of these genes was associated with poorer prognosis in HCC patients. Lower promoter methylation of these genes might cause higher expression levels in tumor tissues of HCC. Genetic alterations and several methylated-CpG sites in these genes were significantly associated with survival. Notably, expression levels of CDK1 , CCNB1 , and CCNB2 were positively correlated with infiltrating levels of CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells in HCC. In addition, significant correlations between the expression of these genes and various immune markers in HCC, such as PD-1, PDL-1, and CTLA-4, were also observed. Conclusions CDK1 , CCNB1 , and CCNB2 are potential prognostic biomarkers and associated with immune cell infiltration in HCC. The genes may be utilized to predict the reaction of immunotherapy. Combining inhibitors of these genes with immunotherapy may improve the survival time of HCC patients.