5-Methylcytosine methylation predicts cervical cancer prognosis, shaping immune cell infiltration

• Published in: Journal of International Medical Research
• Main Authors: Luyang Su, Ren Xu, Yanan Ren, Shixia Zhao, Liyun Song, Cuiqiao Meng, Weilan Liu, Xuan Zhou, Zeqing Du
• Format: Article
• Language: English
• Published: SAGE Publishing 2025-04-01
• Online Access: https://doi.org/10.1177/03000605251328301

Background Epigenetics, encompassing DNA and RNA modifications, has emerged as a prominent area of research in the post-genomic era. Numerous studies have elucidated the impact of epigenetics on tumor regulation. However, the methylation patterns of 5-methylcytosine in cervical cancer as well as its role in the tumor microenvironment and immunotherapy remain poorly understood. Methods Utilizing a comprehensive dataset encompassing samples from 306 patients with cervical cancer from The Cancer Genome Atlas and Gene Expression Omnibus repositories, we conducted an in-depth analysis to evaluate the potential association between the modification patterns of 5-methylcytosine and the infiltration of cells within the tumor microenvironment, taking into account 11 regulators of 5-methylcytosine modification. Subsequently, we employed stepwise regression and Least Absolute Shrinkage and Selection Operator Cox regression to quantify 5-methylcytosine modification patterns in patients with cervical squamous cell carcinoma and endocervical adenocarcinoma, yielding the 5-methylcytosine score. Our study explored the link between the 5-methylcytosine score and clinical characteristics as well as prognostic outcomes in patients with cervical squamous cell carcinoma and endocervical adenocarcinoma. Results A comprehensive analysis of 306 patients with cervical cancer revealed two distinct 5-methylcytosine modification patterns, henceforth labeled as 5-methylcytosine clusters A and B. These clusters exhibited distinct immunological profiles and biological attributes, with 5-methylcytosine cluster A exhibiting a higher degree of immune cell infiltration. Utilizing univariate Cox regression analysis, we identified 367 genes regulated by 5-methylcytosine that were significantly correlated with patient prognosis. This analysis further stratified the samples into three distinct genomic subtypes. Survival analyses indicated that patients belonging to gene cluster C exhibited more favorable survival outcomes than those belonging to gene clusters A and B. Intriguingly, most 5-methylcytosine regulatory factors had higher expression levels in gene cluster B than in gene cluster A. Gene set enrichment analysis of a single sample revealed elevated immune cell infiltration within gene cluster B, indicating a stronger immune response in this cluster. The 5-methylcytosine score feature was utilized to determine the 5-methylcytosine modification pattern in cervical cancer, revealing that patients with low 5-methylcytosine scores exhibited better survival rates, whereas those with high scores had increased mutation frequencies and better treatment responses. Conclusions This research underscores the key role of 5-methylcytosine modification patterns in cervical cancer. Analysis of these patterns will deepen our understanding of the cervical cancer tumor microenvironment, paving the way for the development of more refined and effective immunotherapy strategies.