Zhai Junyu, Li Shang, Li Yu, Du Yanzhi
Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China.
J Cancer. 2021 Jun 5;12(15):4729-4738. doi: 10.7150/jca.50868. eCollection 2021.
We reanalyzed the expression of 16 acknowledged N-methyladenosine (mA) 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 mA 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 expression and increased expression in endometrial adenocarcinoma from our validation cohort was consistent with analysis using TCGA and GEO datasets. In conclusion, mA methylation regulators, especially FTO, RBM15, and YTHDF1, are critical in the progression and prognosis of endometrial adenocarcinoma.
我们使用癌症基因组图谱(TCGA)数据集重新分析了406例子宫内膜腺癌患者和19例对照中16种公认的N-甲基腺苷(mA)RNA调节因子的表达,并使用基因表达综合数据库(GEO)数据集和实时定量聚合酶链反应进一步验证了我们的结果。13种mA RNA甲基化调节因子在子宫内膜腺癌患者和对照之间存在差异表达。FTO、RBM15和YTHDF1被确定为独立的预后标志物,且与子宫内膜癌患者的国际妇产科联盟分级密切相关。GEO数据集也验证了子宫内膜腺癌患者与增生患者之间FTO和RBM15的差异表达。功能富集和 Ingenuity 通路分析网络表明,FTO和RBM15通过IGF1、IRS1、RBM24、LARP1和CBFA2T3对结缔组织发育、分解代谢过程、RNA稳定性、氧化去甲基化、体温稳态和能量代谢的调节,促进了子宫内膜腺癌患者的生存。我们验证队列中子宫内膜腺癌中表达的降低和升高与使用TCGA和GEO数据集的分析结果一致。总之,mA甲基化调节因子,尤其是FTO、RBM15和YTHDF1,在子宫内膜腺癌的进展和预后中至关重要。