Constructing and validating of m7G-related genes prognostic signature for hepatocellular carcinoma and immune infiltration: potential biomarkers for predicting the overall survival

Abstract

Background: To investigate the prognostic significance of N7-methylguanosine (m7G) regulators and immune infiltration in liver hepatocellular carcinoma (LIHC).Methods: The research measured predictive m7G genes in LIHC samples from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Data on the stemness index based on mRNA expression (mRNAsi), gene mutations, and corresponding clinical characteristics were obtained from TCGA and ICGC. Lasso regression was used to construct the prediction model to assess the m7G prognostic signals in LIHC. Based on these genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify key biological functions and pathways. The correlation between m7G RNA methylation regulators and the prognosis and immune infiltration of LIHC was evaluated.Results: There were 21 m7G-related differentially expressed genes (DEGs) in LIHC and healthy tissues, and LIHC patients could be divided into two categories by consensus clustering of these DEGs. A fivegene predictive approach was employed using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Patients in the low-risk group showed a significantly higher survival rate compared with those in the high-risk group (P=0.001). Validations using the ICGC database. Also, univariate and multivariate Cox regression analyses suggested that the risk score produced by the predictive model is an independent predictor for LIHC [hazard ratio (HR): 1.848, 95% confidence interval (CI): 1.286-2.656; HR: 2.597, 95% CI: 1.358-4.965]. The ROC curves of the ICGC cohort revealed that the five-gene prediction model performed well [area under the curve (AUC) =0.642 at 1 year, AUC =0.686 at 2 years, and AUC =0.667 at 3 years]. Immuno-oncology scoring revealed that in the high-risk group, among 16 immune cells, the expressions of neutrophils and natural killer (NK) cells were low and that of regulatory T-cells (Tregs) was high.Conclusions: LIHC occurrence and progression are linked to m7G-related genes.

REST Promotes Autophagy in Gastric Cancer by Transcriptionally Activating FABP6 to Inhibit the Akt/mTOR Signaling Pathway

“…It's also noteworthy that CST6 and DKK1 have been previously implicated in GC. For instance, CST6 is upregulated in the necroptosis-related genes prognostic index-high subgroup of STAD patients and is related to poor prognosis [28]. Similarly, DKK1 has been shown to correlate with poorer sur- vival rates in GC patients, through mechanisms that involve the creation of an immunosuppressive tumor microenvironment [29].…”

Sensitivity Analysis for Survival Prognostic Prediction with Gene Selection: A Copula Method for Dependent Censoring

“…The median was chosen to ensure a desirable statistical power to detect the difference of the two groups and to achieve robust groupings by eliminating the instability due to unevenly allocated sample sizes. Additionally, this rule has been commonly employed in the analysis of survival prognostic prediction with a multi-gene predictor [ 6 , 20 , 25 , 26 ].…”

“…Usually, a multi-gene predictor is more accurate than a single-gene predictor as the prognostic ability of a single gene is limited. A predictor optimally constructed from the selected genes becomes a useful biomarker for predicting survival in breast cancer [ 10 , 11 , 12 , 13 , 14 , 15 ], lung cancer [ 6 , 7 , 8 , 9 , 16 , 17 ], gastric cancer [ 18 , 19 ], ovarian cancer [ 20 , 21 , 22 , 23 , 24 ], skin cancer [ 25 ], liver cancer [ 26 , 27 ], bladder cancer [ 28 ], head and neck cancer [ 29 , 30 ], glioma [ 31 ], myeloproliferative neoplasms [ 32 ], kidney cancer [ 33 ], and cancers of mixed types [ 34 , 35 ]. These analyses were performed mostly based on univariate Cox regression with the significance scaling of p -values, such as 0.05, 0.01, and 0.001, followed by cross-validation and/or external validation.…”

Construction and validation of a prognostic signature for mucinous colonic adenocarcinoma based on N7-methylguanosine-related long non-coding RNAs

“…A variety of studies have shown that m7G METTL1 or WDR4 is involved in regulating the occurrence and development of various cancers, such as liver cancer ( 15 ), head and neck squamous cell carcinoma ( 16 ), bladder cancer ( 17 ), colon cancer ( 18 ) and so on. In addition, m7G-related genes have been used to construct a prognostic model of the liver ( 19 ).…”