RNA 5-Methylcytosine Regulators Contribute to Metabolism Heterogeneity and Predict Prognosis in Ovarian Cancer

• Published in: Frontiers in cell and developmental biology Vol. 10; p. 807786
• Main Authors: Xu, Jie, Liu, Xiaoyi, Chen, Yanjie, Wang, Yuya, Liu, Tao, Yi, Ping
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 18.03.2022
• Subjects: 5-methylcytosine; Cell and Developmental Biology; LASSO cox regression; metabolism heterogeneity; ovarian cancer; RNA modification; RNA modification; 5-methylcytosine; ovarian cancer; LASSO cox regression; metabolism heterogeneity
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2022.807786

5-Methylcytosine (m C) is an abundant and highly conserved modification in RNAs. The dysregulation of RNA m C methylation has been reported in cancers, but the regulatory network in ovarian cancer of RNA m C methylation-related genes and its implication in metabolic regulation remain largely unexplored. In this study, RNA-sequencing data and clinical information of 374 ovarian cancer patients were downloaded from The Cancer Genome Atlas database, and a total of 14 RNA m C regulators were included. Through unsupervised consensus clustering, two clusters with different m C modification patterns were identified with distinct survivals. According to enrichment analyses, glycosaminoglycan and collagen metabolism-related pathways were specifically activated in cluster 1, whereas fatty acid metabolism-related pathways were enriched in cluster 2, which had better overall survival (OS). Besides the metabolism heterogeneity, the higher sensitivity to platinum and paclitaxel in cluster 2 can further explain the improved OS. Ultimately, a least absolute shrinkage and selection operator prediction model formed by ALYREF, NOP2, and TET2 toward OS was constructed. In conclusion, distinct m C modification pattern exhibited metabolism heterogeneity, different chemotherapy sensitivity, and consequently survival difference, providing evidence for risk stratification.