The m6A/m5C/m1A Regulated Gene Signature Predicts the Prognosis and Correlates With the Immune Status of Hepatocellular Carcinoma

Abstract

RNA modification of m6A/m5C/m1A contributes to the occurrence and development of cancer. Consequently, this study aimed to investigate the functions of m6A/m5C/m1A regulated genes in the prognosis and immune microenvironment of hepatocellular carcinoma (HCC). The expression levels of 45 m6A/m5C/m1A regulated genes in HCC tissues were determined. The functional mechanisms and protein–protein interaction network of m6A/m5C/m1A regulated genes were investigated. The Cancer Genome Atlas (TCGA) HCC gene set was categorized based on 45 m6A/m5C/m1A regulated genes, and survival analysis was used to determine the relationship between the overall survival of HCC patients in subgroups. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct the risk model and nomogram for m6A/m5C/m1A regulated genes. The relationships between m6A/m5C/m1A regulated gene subsets and risk model and immune cell infiltration were analyzed using CIBERSORT. m6A/m5C/m1A regulated genes were involved in mRNA and RNA modifications, mRNA and RNA methylation, mRNA and RNA stability, and other processes. There was a statistically significant difference between cluster1 and cluster2 groups of genes regulated by m6A/m5C/m1A. The prognosis of cluster1 patients was significantly better than that of cluster2 patients. There were statistically significant differences between the two cluster groups in terms of fustat status, grade, clinical stage, and T stage of HCC patients. The risk model comprised the overexpression of YBX1, ZC3H13, YTHDF1, TRMT10C, YTHDF2, RRP8, TRMT6, LRPPRC, and IGF2BP3, which contributed to the poor prognosis of HCC patients. The high-risk score was associated with prognosis, fustat status, grade, clinical stage, T stage, and M stage and was an independent risk factor for poor prognosis in HCC patients. High-risk score mechanisms included spliceosome, RNA degradation, and DNA replication, among others, and high-risk was closely related to stromal score, CD4 memory resting T cells, M0 macrophages, M1 macrophages, resting mast cells, CD4 memory activated T cells, and follicular helper T cells. In conclusion, the cluster subgroup and risk model of m6A/m5C/m1A regulated genes were associated with the poor prognosis and immune microenvironment in HCC and are expected to be the new tools for assessing the prognosis of HCC patients.

RNA m5C regulator-mediated modification patterns and the cross-talk between tumor microenvironment infiltration in gastric cancer

“…As for the readers, ALYREF and YBX1 were remarkably overexpressed in GC patients. Research on bladder cancer, breast cancer, HCC, and oral squamous cell carcinoma revealed that ALYREF and YBX1 were upregulated as well ( 22 , 42 – 44 ). Intriguingly, high expression of ALYREF and YBX1 are also significantly correlated with the favorable prognosis of GC patients.…”

“…An increasing number of studies validate that the dynamic modification of m 5 C and its regulators is involved in a series of physiological and pathological processes, including RNA stability, gene expression, and protein synthesis. As for tumor malignant biological behaviors, it has been reported that m 5 C and its regulators play essential roles in the pathogenesis of leukemia ( 21 ), hepatocellular carcinoma (HCC) ( 22 ), glioblastoma multiforme (GBM) ( 12 ), and bladder cancer ( 20 ), indicating the promising prospect of m 5 C modification in cancer treatment.…”

m6A/ m1A /m5C/m7G-related methylation modification patterns and immune characterization in prostate cancer

“…In vitro and in vivo tumor growth, invasion, migration, and the epithelial-mesenchymal transition of cancer cells are all influenced by dynamic RNA methylation and modification events, such as m 6 A, m 1 A, m 5 C and m 7 G (X. Y. Li et al, 2022 ; Traube et al, 2017 ). In addition to playing essential roles in various cancers and anticancer effects, modification events can also be used as prognostic indicators ( Mahmoud and Ali, 2019 ).…”

“…Variations in mRNA transcriptomes between different methylation subtypes were strongly linked with biological pathways involved in MRG and the immune system ( Gu et al, 2021 ; X. Y. Li et al, 2022 ). We determined two gene subtypes relied on the DEGs between the two methylation subtypes.…”

“…PCa patients’ prognoses are poor. There were significant differences between patient subgroups in terms of TME, immunological checkpoints, CSC index, prognosis, mutation, and therapy susceptibility after standard therapy because of high levels of checkpoints, lymphocytes that infiltrate tumors, and tumor neoantigens (D. Li et al, 2022 ). Despite recent developments in immunotherapy, patients with PCa still experience heterogeneity in their results, underlining the important role of TME in the growth and development of PCa tumors ( Yu et al, 2022 ).…”