Cancer stem cells (CSCs) represent a small but critical subpopulation of tumor cells that drive therapy resistance, relapse and metastasis. Gastric cancer stem cells (GCSCs) have been identified through surface markers and transcriptional signatures, revealing their central role in tumor progression. Recently, N6-methyladenosine (m6A) RNA modification has emerged as a crucial epitranscriptomic regulator of CSC biology. The m6A machinery, including “writers” (METTL3, METTL14, WTAP, VIRMA), “erasers” (FTO, ALKBH5) and “readers” (YTHDFs/ YTHDCs, IGF2BPs, hnRNPA2B1), orchestrates RNA stability, splicing, translation and decay, thereby influencing self-renewal and oncogenic signaling. In GCSCs, m6A controls pluripotency factors, oncogenic transcripts and non-coding RNAs, collectively reinforcing stemness and malignant potential. Mounting evidence implicates dysregulated m6A effectors as not only key drivers of GCSC biology but also as promising biomarkers for patient stratification and therapeutic targets capable of selectively eliminating CSCs. Harnessing this knowledge could enable earlier diagnosis, more accurate patient stratification and more precise treatments. However, challenges remain regarding the resolution of m6A profiling, therapeutic selectivity to avoid unwanted toxicity and biomarker validation for clinical use. This review summarizes the discovery and features of CSCs, highlights the functional role of m6A in GCSCs, and explores diagnostic and therapeutic opportunities while outlining key difficulties for clinical translation.
癌症干细胞（CSCs）是肿瘤细胞中一个数量虽少但至关重要的亚群，它们驱动着治疗抵抗、复发和转移。通过表面标志物和转录特征，胃癌干细胞（GCSCs）已被识别，揭示了它们在肿瘤进展中的核心作用。近年来，N6-甲基腺苷（m6A）RNA修饰已成为调控癌症干细胞生物学的重要表观转录组调节因子。m6A机制，包括“写入器”（METTL3、METTL14、WTAP、VIRMA）、“擦除器”（FTO、ALKBH5）和“读取器”（YTHDFs/YTHDCs、IGF2BPs、hnRNPA2B1），协调RNA的稳定性、剪接、翻译和降解，从而影响自我更新和致癌信号传导。在GCSCs中，m6A调控多能性因子、致癌转录本和非编码RNA，共同增强干性和恶性潜能。越来越多的证据表明，失调的m6A效应因子不仅是GCSC生物学的关键驱动因素，也是患者分层的有前景的生物标志物，以及能够选择性消除CSCs的治疗靶点。利用这些知识可能实现更早的诊断、更准确的患者分层和更精准的治疗。然而，在m6A分析的分辨率、避免不必要毒性的治疗选择性以及临床应用的生物标志物验证方面，仍存在挑战。本综述总结了CSCs的发现和特征，重点阐述了m6A在GCSCs中的功能作用，并探讨了诊断和治疗机会，同时概述了临床转化的主要困难。
肿瘤(癌症)患者之家