Comprehensive Analysis of m7G-Related Genes and Chronic Hepatitis B: Diagnostic Markers, Immune Microenvironment Regulation, Disease Progression.

Chronic hepatitis B (CHB) is a major public health problem in the world. It is the main cause of liver cirrhosis and liver cancer. Although many important roles of RNA modification in stem cells or tumor diseases have been identified, the role of N7-methylguanosine (m7G) modification in the process of chronic HBV infection has not been clearly defined. Therefore, we conducted a systematic analysis on the process of chronic HBV infection. We found that a total of 18 m7G-related genes were altered in chronic HBV infection, and then we screened out CHB potential diagnostic biomarkers using machine learning and random forest methods. RT-qPCR was performed on the samples of healthy people and CHB, which further verified the possibility of being a diagnostic marker. Then, we typed CHB patients based on these 18 genes. We found that the immune microenvironment of different subtypes was different. Among them, patients with subtype-Ⅰ had severe immune response, that is, relatively serious immune cell infiltration, rich immune pathways, relatively many HLA genes, and immune checkpoints. Finally, we conducted an in-depth discussion on our m7G-related genes, and found that m7G gene related to immune cell infiltration may be involved in the disease progression of CHB patients, which was also confirmed in the GSE84044 dataset. In conclusion, m7G-related genes can not only serve as diagnostic markers of CHB, but also participate in the regulation of immune microenvironment and play an important role in the progression of CHB.

Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer.

Necroptosis is a novel type of regulated cell death that is intimately associated with a variety of tumors. However, how necroptosis affects the identification of gastric cancer (GC) remains unclear. Here we seek to find new potential necroptosis-related biomarkers to predict GC prognosis and immunotherapy effect. We used Cox analysis to obtain shared prognostic markers related to necroptosis from five datasets (TCGA and four GEO datasets). Then, a necroptosis-related gene prognostic score (NRGPS) system was constructed using LASSO Cox regression, NRGPS consisting of three necroptosis-related mRNAs (AXL, RAI14, and NOX4) was identified, 31 pairs of GC and adjacent normal tissues from the Second Hospital of Harbin Medical University were collected and Real-Time Quantitative PCR (RT-qPCR) was used to detect the relative expression levels of the three necroptosis-related mRNAs, and external validation was performed on four GEO datasets (GSE84437, GSE26901, GSE62254 and GSE15459). In this study, Overall survival (OS) in the high-NRGPS group was significantly lower than in the low-NRGPS group. Cox regression analyses showed that NRGPS was an independent prognostic variable. Tumor-mutation-burden (TMB), tumor microenvironment (TME), microsatellite instability (MSI), and Tumor Immune Dysfunction and Exclusion (TIDE) scoring were used as predictors of the immunotherapy response. A cancer-friendly immune microenvironment, a high TIDE score, a low TMB, and a low MSI were all characteristics of the high-NRGPS group, and they all consistently showed that the issues seen there are related to immune escape in GC. The combination of three candidate genes may be an effective method for diagnostic assessment of GC prognosis and immunotherapy efficacy.