Aim: The search for prognostic biomarkers and the construction of a prognostic risk model for hepatocellular carcinoma (HCC) based on N7-methyladenosine (m7G) methylation regulators.Methods: HCC transcriptomic data and clinical data were obtained from The Cancer Genome Atlas database and Shanghai Ninth People’s Hospital, respectively. m7G methylation regulators were extracted, differential expression analysis was performed using the R software “limma” package, and one-way Cox regression analysis was used to screen for prognostic associations of m7G regulators. Using multi-factor Cox regression analysis, a prognostic risk model for HCC was constructed. Each patient’s risk score was calculated using the model, and patients were divided into high- and low-risk groups according to the median risk score. Cox regression analysis was used to verify the validity of the model in the prognostic assessment of HCC in conjunction with clinicopathological characteristics.Results: The prognostic model was built using the seven genes, namely, CYFIP1, EIF4E2, EIF4G3, GEMIN5, NCBP2, NUDT10, and WDR4. The Kaplan–Meier survival analysis showed poorer 5-years overall survival in the high-risk group compared with the low-risk group, and the receiver-operating characteristic (ROC) curve suggested good model prediction (area under the curve AUC = 0.775, 0.820, and 0.839 at 1, 3, and 5 years). The Cox regression analysis included model risk scores and clinicopathological characteristics, and the results showed that a high-risk score was the only independent risk factor for the prognosis of patients with HCC.Conclusions: The developed bioinformatics-based prognostic risk model for HCC was found to have good predictive power.

BackgroundNecroptosis, a form of programmed cell death, is increasingly being investigated for its controversial role in tumorigenesis and progression. Necroptosis suppresses tumor formation and tumor development by killing tumor cells; however, the necrotic cells also promote tumor formation and tumor development via the immunosuppressive effect of necroptosis and inflammatory response caused by cytokine release. Thus, the exact mechanism of necroptosis in pan-cancer remains unknown.MethodsThe data of 11,057 cancer samples were downloaded from the TCGA database, along with clinical information, tumor mutation burden, and microsatellite instability information of the corresponding patients. We used the TCGA data in a pan-cancer analysis to identify differences in mRNA level as well as single nucleotide variants, copy number variants, methylation profiles, and genomic signatures of miRNA-mRNA interactions. Two drug datasets (from GDSC, CTRP) were used to evaluate drug sensitivity and resistance against necroptosis genes.ResultsNecroptosis genes were aberrantly expressed in various cancers. The frequency of necroptosis gene mutations was highest in lung squamous cell carcinoma. Furthermore, the correlation between necroptosis gene expression in the tumor microenvironment and immune cell infiltration varied for different cancers. High necroptosis gene expression was found to correlate with NK, Tfh, Th1, CD8_T, and DC cells. These can therefore be used as biomarkers to predict prognosis. By matching gene targets with drugs, we identified potential candidate drugs.ConclusionOur study showed the genomic alterations and clinical features of necroptosis genes in 33 cancers. This may help clarify the link between necroptosis and tumorigenesis. Our findings may also provide new approaches for the clinical treatment of cancer.