Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
School of Physical Education, Jinan University, Guangzhou, China.
Clin Exp Pharmacol Physiol. 2021 Feb;48(2):270-278. doi: 10.1111/1440-1681.13412. Epub 2020 Oct 21.
The mortality caused by cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) ranks second among female malignant tumour deaths, but their diagnostic and therapeutic targets are still limited. N6-methyladenosine (m6A) is the most common and extensive modification in mRNA molecules, and its methylation regulators participate in regulating the occurrence and development of many tumours. However, whether m6A RNA methylation regulators can be used as independent prognostic indicators of CESC remains unknown. This study unveiled differential expression of 20 m6A RNA methylation regulators between normal and CESC tumour samples, which RNA sequence data and clinical information were obtained from TCGA database. As a result, five m6A RNA methylation regulators (FTO, HNRNPA2B1, RBM15, IGF2BP1, IGF2BP3) were identified to be significantly linked to CESC tumour status. After Lasso cox regression analysis, six m6A RNA methylation regulators (YTHDC2, YTHDC1, ALKBH5, ZC3H13, RBMX, YTHDF1) were chosen to construct a risk signature. CESC patients were then classified as high-risk and low-risk group based on the median risk score. The overall survival (OS) of the CESC patients in high-risk group was significantly lower than that in low-risk group, and the area under curve (AUC) is 0.718. Moreover, the risk model can be an independent prognosis factors for CESC patients and can predict OS of CESC patients with different clinical factors. In conclusion, m6A RNA methylation regulators are closely correlated with CESC clinical characteristics and the selected six m6A RNA methylation regulators may be useful for CESC patients personalized treatment.
由宫颈鳞状细胞癌和宫颈内膜腺癌（CESC）引起的死亡率在女性恶性肿瘤死亡中排名第二，但它们的诊断和治疗靶点仍然有限。N6-甲基腺苷（m6A）是 mRNA 分子中最常见和广泛的修饰，其甲基化调节剂参与调节许多肿瘤的发生和发展。然而，m6A RNA 甲基化调节剂是否可以作为 CESC 的独立预后指标尚不清楚。本研究在 TCGA 数据库中获得正常和 CESC 肿瘤样本的 RNA 序列数据和临床信息，揭示了 20 种 m6A RNA 甲基化调节剂在正常和 CESC 肿瘤样本中的差异表达。结果表明，5 种 m6A RNA 甲基化调节剂（FTO、HNRNPA2B1、RBM15、IGF2BP1、IGF2BP3）与 CESC 肿瘤状态显著相关。经过 Lasso cox 回归分析，选择了 6 种 m6A RNA 甲基化调节剂（YTHDC2、YTHDC1、ALKBH5、ZC3H13、RBMX、YTHDF1）构建风险特征。然后根据中位风险评分将 CESC 患者分为高危和低危组。高危组 CESC 患者的总生存率（OS）明显低于低危组，曲线下面积（AUC）为 0.718。此外，该风险模型可作为 CESC 患者的独立预后因素，可预测不同临床因素的 CESC 患者的 OS。总之，m6A RNA 甲基化调节剂与 CESC 临床特征密切相关，所选的 6 种 m6A RNA 甲基化调节剂可能对 CESC 患者的个体化治疗有用。
