Comprehensive immunohistochemical analysis of N6-methyladenosine (m6A) writers, erasers, and readers in endometrial cancer

Purpose: 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). Methods: : 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. Results: : 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. Conclusion: Overall, our study points towards dysregulated m6A modification in EC and its possibility to serve as a promising prognostic biomarker.