Prognostic signature and immune efficacy of m¹A‐, m⁵C‐ and m⁶A‐related regulators in cutaneous melanoma

Abstract

Cutaneous melanoma (CM) is an aggressive cancer; given that initial and specific signs are lacking, diagnosis is often late and the prognosis is poor. RNA modification has been widely studied in tumour progression. Nevertheless, little progress has been made in the signature of N1‐methyladenosine (m1A), 5‐methylcytosine (m5C), N6‐methyladenosine (m6A)‐related regulators and the tumour microenvironment (TME) cell infiltration in CM. Our study identified the characteristics of m1A‐, m5C‐ and m6A‐related regulators based on 468 CM samples from the public database. Using univariate, multivariate and LASSO Cox regression analysis, a risk model of regulators was established and validated by a nomogram on independent prognostic factors. The gene set variation analysis (GSVA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) clarified the involved functional pathways. A combined single‐sample gene set enrichment analysis (ssGSEA) and CIBERSORT approach revealed TME of regulator‐related prognostic signature. The nine‐gene signature stratified the patients into distinct risk subgroups for personalized prognostic assessment. Additionally, functional enrichment, immune infiltration and immunotherapy response analysis indicated that the high‐risk group was correlated with T‐cell suppression, while the low‐risk group was more sensitive to immunotherapy. The findings presented here contribute to our understanding of the TME molecular heterogeneity in CM. Nine m1A‐, m5C‐ and m6A‐related regulators may also be promising biomarkers for future research.

An integrated model of acinar to ductal metaplasia-related N7-methyladenosine regulators predicts prognosis and immunotherapy in pancreatic carcinoma based on digital spatial profiling

“…It is well known that the degree of immune cell infiltration is closely related to the efficacy of immunotherapy and the prognosis of cancer patients. Studies have found that immune cell infiltration was regulated by a variety of epigenetic factors, including m6a and m5c methylation ( 37 ). But as a newer type of methylation, there are few immune-related studies on m7G methylation.…”

Construction of a Ferroptosis-Related Gene Signature for Predicting Survival and Immune Microenvironment in Melanoma Patients

“…28 Wu et al constructed a prediction model for SKCM, but the sample size of the validation set was too small to represent the accuracy of the model. 29 Two genes (ALOX5, CHAC1) collaborated to create a prognosis model that accurately estimated the prognosis of patients with SKCM, according to our findings. Furthermore, differences in the underlying diseases of SKCM have no impact on the expression features of the two genes, meaning that the prognosis model should be used to ALOX5 is a member of the arachidonic acid-derived family of proinflammatory lipid mediators.…”

A Novel Necroptosis-Related Gene Signature in Skin Cutaneous Melanoma Prognosis and Tumor Microenvironment

“…Before us, most literature concerning the prognostic gene signatures of SKCM was focused on m1A-, m5C-, and m6A-methylation ( Wu et al, 2021 ); autophagy ( Deng et al, 2021 ); ferroptosis ( Xu et al, 2021 ); pyroptosis ( Ju et al, 2021 ); and oxidative stress ( Yang et al, 2021 ). For example, Yang et al built an oxidative stress–associated gene’s prognostic model for melanoma.…”