Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany.
Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany.
J Cancer Res Clin Oncol. 2023 Jun;149(6):2417-2424. doi: 10.1007/s00432-022-04083-1. Epub 2022 Jun 22.
N6-methyladenosine (m6A) is the most frequent type of messenger RNA (mRNA) modification and is implicated in diverse physiological processes. The procedure of m6A RNA modification is regulated by a dynamic interaction of writers (METTL3, METTL4, METTL14, WTAP, KIAA1429), erasers (FTO, ALKBH5), and readers (HNRNPA2B1, HNRNPC, YTHDC1, YTHDC1, YTHDF1-3). In the oncological context, alterations in m6A were identified to be critically involved in tumorigenesis, proliferation, angiogenesis, and drug resistance across diverse cancer entities including endometrial cancer (EC).
In this study, we comprehensively examined the protein expression of m6A writers, readers and erasers by immunohistochemical staining in a cohort of N = 65 EC patients. Protein expression data were analyzed with regard to clinical outcomes.
We identified enhanced protein expression levels of METTL3, METTL14, FTO, HNRNPA2B1, and HNRNPC, respectively to be of prognostic value and linked to a shortened overall survival in EC.
Overall, our study points toward dysregulated m6A modification in EC and its possibility to serve as a promising prognostic biomarker.
N6-甲基腺苷（m6A）是最常见的信使 RNA（mRNA）修饰类型，参与多种生理过程。m6A RNA 修饰的过程受作家（METTL3、METTL4、METTL14、WTAP、KIAA1429）、橡皮擦（FTO、ALKBH5）和读者（HNRNPA2B1、HNRNPC、YTHDC1、YTHDC1、YTHDF1-3）的动态相互作用调节。在肿瘤学背景下，m6A 的改变被确定在肿瘤发生、增殖、血管生成和耐药性中起关键作用，涉及多种癌症实体，包括子宫内膜癌（EC）。
本研究通过免疫组织化学染色，在 N=65 例 EC 患者的队列中全面研究了 m6A 作家、读者和橡皮擦的蛋白表达情况。对蛋白表达数据进行了临床结果分析。
我们发现 METTL3、METTL14、FTO、HNRNPA2B1 和 HNRNPC 的蛋白表达水平分别增强，具有预后价值，并与 EC 的总生存期缩短相关。
总的来说，我们的研究表明 EC 中存在 m6A 修饰失调，并可能作为有前途的预后生物标志物。
