Novel DNA Damage-Related Subtypes Characterization Identifies Uterine Corpus Endometrial Carcinoma (UCEC) Based on Machine Learning

Abstract

Objective. Accumulating evidence suggests that DNA damage is associated with numerous gynecological illnesses, particularly advanced uterine corpus endometrial carcinoma (UCEC), illustrating the involvement of the DNA damage pathway in the advancement of UCEC. This research aimed to discover a robust subtype with the potential to contribute to the scientific treatment of UCEC. Methods. In this work, the expression patterns of prognostic DNA damage-related genes were curated, and consensus clustering analyses were undertaken to determine DNA damage subtypes in patients with UCEC in the TCGA cohort. Two DNA damage-related subtypes were identified for further investigation. Differentially expressed genes (DEGs) analysis, gene ontology analysis, mutation analysis, and immune cell infraction analysis were performed to find the molecular mechanism behind it. Finally, the polymerase chain reaction (PCR) was conducted to verify the correlation of the hub genes. Results. In total, 545 patients with UCEC were tested for two distinct DNA damage subtypes. The clinical prognosis was poorer among patients with DNA damage subtype 2 than those in subtype 1. The DEGs analysis and PPI analysis showed that ASMP, BUB1, CENPF, MAD2L1, NCAPG, SGO2, and TOP2A were expressed higher in UCEC tissues than in the normal tissues. Immune cell infraction analysis showed that hub genes were associated with the tumor microenvironment (TME). Conclusion. Altogether, our research identified two distinct DNA damage subtypes that are complicated and heterogeneous. A better knowledge of the characteristics of the TME may be gained by quantitative measurement of DNA damage subtypes in individual patients, which can also lead to the development of more successful treatment regimens.