Significance of N6-Methyladenosine RNA Methylation Regulators in Immune Infiltrates of Ovarian Cancer

Abstract

N6-methyladenosine (m6A) RNA methylation regulators play an important role in the occurrence and development of tumors. Here, we aimed to identify the potential roles of m6A RNA methylation regulators in immune infiltrates of ovarian cancer. We obtained two distinct m6A patterns (m6Acluster.A and m6Acluster.B) based on the expression levels of all 21 m6A RNA methylation regulators from The Cancer Genome Atlas (TCGA) database using a consensus clustering algorithm. Differential analysis of m6Acluster.A and m6Acluster.B identified 196 m6A-related genes. We further validated the m6A regulation mechanism based on the 196 m6A-related genes using another consensus clustering algorithm. Considering individual differences, principal component analysis algorithms were used to calculate an m6A score for each sample in order to quantify the m6A patterns. A low m6A score was associated with immune activation and enhanced response to immune checkpoint inhibitors, whereas a high m6A score was associated with tumor progression. Finally, we successfully verified the correlation between m6A regulators and immune microenvironment in OC using our microarray analysis data. In summary, m6A regulators play non-negligible roles in immune infiltrates of ovarian cancer. Our investigation of m6A patterns may help to guide future immunotherapy strategies for advanced ovarian cancer.

The m6A-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Tumor Immune Infiltration in Ovarian Cancer

“…Furthermore, the expression of PD-L2 was higher in Cluster 2, which suggested that Cluster 1 respond more sensitively to ICIs. How m6A modification influences the tumor microenvironment, especially the TIIC types, has been researched [ 42 , 69 , 70 ]; our study might provide more evidence for further research.…”

The potential regulatory role of RNA methylation in ovarian cancer

“…Using various biological investigations, 21 m6A regulators were divided into two groups: those with low m6A scores and those with high m6A scores. Low m6A scores were associated with immune infiltration and responses to immune detection site inhibitors (ICIs) [ 91 ]. RNA modification patterns in ovarian cancer characterized by high immune infiltration and immune activation showed higher RNW scores, which were able to predict patient response to immunotherapy [ 74 ].…”

Roles of N6-methyladenosine (m6A) modifications in gynecologic cancers: mechanisms and therapeutic targeting

“…Despite the relatively high tumor mutation burden in OC, it is a cold tumor, generally lacking the infiltration of cytotoxic T lymphocytes, and thereby lacking the ability to recognize all the tumor antigens [78]. Numerous studies have demonstrated that the degree of immune cell infiltration and expression levels of various immune gene markers are correlated with the specific m 6 A regulators [54,[79][80][81]. Wang et al reported RBM15B, Zinc finger CCCH domain-containing protein 13 (ZC3H13), YTHDF1, and IGF2BP1 as important immune cell infiltration-regulated m 6 A regulators in the OC [79].…”