Data mining analysis of the prognostic impact of N⁶-methyladenosine regulators in patients with endometrial adenocarcinoma

Abstract

We reanalyzed the expression of 16 acknowledged N 6 -methyladenosine (m 6 A) RNA regulators in 406 endometrial adenocarcinoma patients and 19 controls using The Cancer Genome Atlas (TCGA) dataset, and further verified our results using Gene Expression Omnibus (GEO) dataset and real-time quantitative polymerase chain reaction. Thirteen m 6 A RNA methylation regulators were differentially expressed between patients with endometrial adenocarcinoma and controls. FTO, RBM15, and YTHDF1, were identified as independent prognostic markers and closely associated with International Federation of Gynecology and Obstetrics grade in endometrial cancer patients. GEO dataset also verified the differential expression of FTO and RBM15 between patients with endometrial adenocarcinoma and hyperplasia. Functional enrichment and ingenuity pathway analysis network suggested that FTO and RBM15 contributed to the survival of patients with endometrial adenocarcinoma via the regulation of connective tissue development, catabolic process, RNA stability, oxidative demethylation, temperature homeostasis, and energy metabolism through IGF1, IRS1, RBM24, LARP1, and CBFA2T3. The decreased FTO expression and increased RBM15 expression in endometrial adenocarcinoma from our validation cohort was consistent with in silico analysis using TCGA and GEO datasets. In conclusion, m 6 A methylation regulators, especially FTO, RBM15, and YTHDF1, are critical in the progression and prognosis of endometrial adenocarcinoma.

Role of m6A modification in female infertility and reproductive system diseases

“…The expression of KIAA1429 observed in EC was significantly decreased, leading to the reduction of m6A levels [84]. KIAA1429 gene expression is associated with cellular nucleic metabolism.…”

Emerging Roles of m6A RNA Methylation Regulators in Gynecological Cancer

“…FTO, RBM15, and YTHDF1 were identified as independent prognostic markers for endometrial cancer, and FTO and RBM15 were differentially expressed between endometrial adenocarcinoma and hyperplasia. These data suggest that FTO, RBM15, and YTHDF1 are critical in the progression and prognosis of endometrial cancer (82,97). Interestingly, Zhang et al found that CpG sites located at the m 6 A regulatory site may be considered a potential prognostic feature of endometrial cancer patients (98).…”

RNA m6A methylation regulators in endometrial cancer (Review)

“…According to Zhai et al ( 142 ), RBM15/15B, YTHDF1 and IGF2BP1/2 are upregulated in endometrial adenocarcinoma. By contrast, FTO, KIAA1429, METTL14, ZC3H13 and YTHDC1 expression was downregulated.…”