Gene signatures, immune infiltration, and drug sensitivity based on a comprehensive analysis of m6a RNA methylation regulators in cervical cancer

Background Cervical cancer is the fourth most common cancer in women. N 6 -dimethyladenosine (m 6 A) mRNA methylation is closely associated with cervical cancer. Methods Using TCGA database, we studied the expression and mutation of m 6 A-related genes in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and obtained genetic characteristics based on an m 6 A risk model and prognostic value of m 6 A. We studied the effects of the m 6 A risk score on immune features and genomic changes of patients with CESC, evaluated the sensitivity of patients with CESC to different small-molecule drugs based on the m 6 A risk score, and established a clinical prediction model. Results Ten m 6 A-related genes were differentially expressed between CESC and normal tissues. High-risk patients had a low overall survival (OS) and significantly low immune scores but showed no significantly altered stromal scores. The tumor mutation burden (TMB) and tumor neoantigen levels significantly differed between the high- and low-risk groups. In the high-risk group, copy number variation (CNV) changes mainly led to gene amplification, while in the low-risk group, CNV changes primarily manifested as gene copy number deletions. ZC3H13 expression was low in CESC tissues. ZC3H13 knockdown promoted CESC cell proliferation, migration, and invasion, reducing the RNA methylation levels. Rapamycin suppressed the CESC cell proliferation, migration, and invasion abilities, increasing the m 6 A levels. Conclusion m 6 A mRNA methylation is closely related to the occurrence, development, immune invasion, drug sensitivity, and prognosis of cervical cancer. The prognostic m 6 A feature model of m 6 A signature genes can accurately predict the OS of patients with CESC. Drugs targeting factors regulating m 6 A mRNA methylation might offer a good prospect for treating cervical cancer.