m6A RNA methylation regulator-based signature for prognostic prediction and its potential immunological role in uterine corpus endometrial carcinoma

Background: Uterine corpus endometrial carcinoma (UCEC) is the most common female pelvic malignancy worldwide. N6-methyladenosine (m(6)A) plays an important role in various cellular responses, especially in cancer progression. However, the correlation between prognostic UCEC and m(6)A RNA methylation regulators remains unclear. Methods: We used The Cancer Genome Atlas (TCGA) to provide a gene signature that could improve the prognostic evaluation of UCEC patients according to the distinct genetic trait of m(6)A RNA methylation regulators from a bioinformatics perspective. After comparing UCEC subgroups with different genetic profiles of m(6)A regulators, we identified 71 differentially expressed genes associated with overall survival (OS) and generated a nine-gene signature through least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Finally, we used in vitro and in vivo tumor cell experiments as well as the immune correlation analysis to verify the function of each gene in the proposed gene signature. Results: Time-dependent receiver operating characteristic (ROC) curves revealed that the proposed gene signature could predict the outcome of UCEC patients accurately. We found that CDKN2A mainly acted from the perspective of tumor cells, while COL4A4, PXDN, TIGIT, CHODL, LMO3, KCNJ12, L1CAM, and EPHB1 might play a role in UCEC from an immunological point of view. Conclusions: From an epigenetics perspective, the m6A RNA methylation regulator-based gene signature can predict the prognosis of UCEC patients and immune therapeutic efficacy.