Construction and Validation of a m7G-Related Gene-Based Prognostic Model for Gastric Cancer

Abstract

BackgroundGastric cancer (GC) is one of the most common malignant tumors of the digestive system. Chinese cases of GC account for about 40% of the global rate, with approximately 1.66 million people succumbing to the disease each year. Despite the progress made in the treatment of GC, most patients are diagnosed at an advanced stage due to the lack of obvious clinical symptoms in the early stages of GC, and their prognosis is still very poor. The m7G modification is one of the most common forms of base modification in post-transcriptional regulation, and it is widely distributed in the 5′ cap region of tRNA, rRNA, and eukaryotic mRNA.MethodsRNA sequencing data of GC were downloaded from The Cancer Genome Atlas. The differentially expressed m7G-related genes in normal and tumour tissues were determined, and the expression and prognostic value of m7G-related genes were systematically analysed. We then built models using the selected m7G-related genes with the help of machine learning methods.The model was then validated for prognostic value by combining the receiver operating characteristic curve (ROC) and forest plots. The model was then validated on an external dataset. Finally, quantitative real-time PCR (qPCR) was performed to detect gene expression levels in clinical gastric cancer and paraneoplastic tissue.ResultsThe model is able to determine the prognosis of GC samples quantitatively and accurately. The ROC analysis of model has an AUC of 0.761 and 0.714 for the 3-year overall survival (OS) in the training and validation sets, respectively. We determined a correlation between risk scores and immune cell infiltration and concluded that immune cell infiltration affects the prognosis of GC patients. NUDT10, METTL1, NUDT4, GEMIN5, EIF4E1B, and DCPS were identified as prognostic hub genes and potential therapeutic agents were identified based on these genes.ConclusionThe m7G-related gene-based prognostic model showed good prognostic discrimination. Understanding how m7G modification affect the infiltration of the tumor microenvironment (TME) cells will enable us to better understand the TME’s anti-tumor immune response, and hopefully guide more effective immunotherapy methods.

Phosphorylation of T897 in the dimerization domain of Gemin5 modulates protein interactions and translation regulation

“…The interaction between Gemin5 and the cap-binding protein eIF4E [46] as well as the direct recognition of the cap structure of snRNAs by Gemin5 [15] prompted us to seek the involvement of Gemin5 in RNA cap-binding complexes. Recent studies identified Gemin5 as one of the m 7 G methylation-related genes, also including CYFIP1, EIF4E2, EIF4E1B, EIF4G3, NCBP2, NUDT10, NUDT4, WDR4, METTL1, and DCP s. These genes are biomarkers for predicting overall survival outcomes in hepatocellular carcinoma and gastric cancer [48] , [49] . Noteworthy, Gemin5 knockout has been shown to be detrimental in animal models, including mouse and drosophila [17] , [24] .…”

Identification of N7-methylguanosine related subtypes and construction of prognostic model in gastric cancer

“…Li et al. ( 33 ) have also done related work, but our analysis is more in-depth and comprehensive than their study. First of all, compared with that literature, this study analyzed the somatic mutations of m7GRGs in GC patients, including SNV and CNV.…”

M7G-related molecular subtypes can predict the prognosis and correlate with immunotherapy and chemotherapy responses in bladder cancer patients

“…As a part of a scaffold component of eukaryotic translation initiation factor 4F, eukaryotic translation initiation factor 4G 1 (EIF4G1) is closely associated with various tumors, especially in solid tumors [ 27 ]. Nudix hydrolase 10 (NUDT10), located in Xp11.22, increases promoter methylation and is associated with OS in prostate cancer and gastric cancer [ 28 , 29 ]. NUDT10 and Nudix hydrolase 11 (NUDT11) can promote prostate carcinogenesis and increase prostate cancer susceptibility by being involved in a variety of biological processes and mediating cellular stress responses [ 30 ].…”