J Cancer 2021; 12(15):4729-4738. doi:10.7150/jca.50868

Research Paper

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

Junyu Zhai1,2#, Shang Li1,2#, Yu Li3, Yanzhi Du1,2✉

1. Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China.
2. Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China.
3. Department of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
#These authors contributed equally to this work.

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Zhai J, Li S, Li Y, Du Y. Data mining analysis of the prognostic impact of N6-methyladenosine regulators in patients with endometrial adenocarcinoma. J Cancer 2021; 12(15):4729-4738. doi:10.7150/jca.50868. Available from https://www.jcancer.org/v12p4729.htm

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We reanalyzed the expression of 16 acknowledged N6-methyladenosine (m6A) 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 m6A 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, m6A methylation regulators, especially FTO, RBM15, and YTHDF1, are critical in the progression and prognosis of endometrial adenocarcinoma.

Keywords: N6-methyladenosine, Endometrial Adenocarcinoma, Energy Metabolism, RNA-Binding Protein