The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

Abstract

Long noncoding RNAs (lncRNAs) are closely associated with a variety of tumors, including stomach adenocarcinoma (STAD). However, the role of 5-methylcytosine- (m5C-) related lncRNAs in STAD is still uncertain. This study investigated the value of m5C-related lncRNAs in prognostic evaluation and immunotherapy of STAD. STAD transcriptome sequencing data were downloaded from The Cancer Genome Atlas (TCGA) database, and m5C-related lncRNAs were screened by Pearson correlation analysis. A prognostic m5C-related lncRNA signature (m5CRLSig) associated with STAD was established using univariate and multivariate Cox regression analysis. We constructed a prognostic risk model for STAD with six m5C-related lncRNAs. The receiver operating characteristic (ROC) curve was used to examine the predictive efficacy. Univariate and multifactorial Cox regression analysis and principal component analysis (PCA) validated m5CRLSig as an independent factor of STAD prognosis. The clinicopathological characteristics of the model showed higher risk scores for stages II-IV, grade 3, N1-3, and death status. The calibration curve of a nomogram revealed that the nomogram had an excellent predictive function for survival risk. Furthermore, the expression of six m5C-related lncRNAs in STAD and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR), which verified the feasibility of the m5CRLSig as a prognostic marker for STAD. m5C-related lncRNAs were linked to multiple immune-associated pathways, according to gene set enrichment analysis (GSEA). CIBERSORT analysis indicated that m5CRLSig was involved in immune cell infiltration. Risk score was associated with immune checkpoint gene expression, immune function scores, and chemotherapeutic drug sensitivity. Therefore, m5CRLSig can efficiently assess the prognosis of STAD patients and can be used as a biological marker for immunotherapy.

The lncRNA epigenetics: The significance of m6A and m5C lncRNA modifications in cancer

“…Overall, the relevant emerging information is that the m5C-related lncRNA signature predicts the patients’ OS. Future directions and clinical studies will unveil whether these lncRNAs could be used as biomarkers and therapeutic targets ( 83 – 91 ). Moreover, the signature is supported by a previous 2020’s pan-cancer study showing that lncRNAs could work as biomarkers including breast, pancreatic, lung and hepatocellular carcinoma ( 92 ).…”

Vital roles of m5C RNA modification in cancer and immune cell biology

“…The role of m 5 C RNA modification in GC is generally oncogenic, with high levels of m 5 C indicating poor prognosis and a low overall survival (OS) rate ( 126 ). Modifications of both mRNA ( 30 , 34 , 51 ) and lncRNA ( 126 , 139 ) have been observed during GC progression, and risk models based on m 5 C levels were developed for prognosis prediction ( 139 ). NSUN2 is the main oncogenic m 5 C-methyltransferase in GC, targeting the mRNAs of PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) ( 34 ), PCYT1A (phosphate cytidylyltransferase 1 choline-alpha) ( 34 ), FOXC2 (Forkhead box protein C2) ( 51 ) and p57 Kip2 (a type of cyclin-dependent kinase (CDK) inhibitor) ( 30 ).…”

Identification of a novel m5C/m6A-related gene signature for predicting prognosis and immunotherapy efficacy in lung adenocarcinoma

“…We collected m5C/m6A-related genes from previous studies on RNA modifications (Zhang et al, 2021;He et al, 2022). These 23 m6A-related and 13 m5C-related genes are listed in Table 1.…”