RNA‑binding proteins as epithelial transcriptome orchestrators in gastric cancer: Immune‑metabolic crosstalk and therapeutic vulnerability (Review).

Among malignant tumors, gastric cancer (GC) ranks fifth in terms of global incidence and third in terms of the number of related deaths, and its high molecular heterogeneity, chemoresistance and lack of targeted therapies remain major clinical challenges. RNA‑binding proteins (RBPs), as the core effectors in post‑transcriptional regulation, are widely involved in the determination of malignant phenotypes in GC; they act by dynamically regulating RNA splicing, stability, translation and modification, in addition to mediating the crosstalk between metabolism and immunity, and influencing proliferation, metastasis, drug resistance and other malignant phenotypes. However, the functional controversy of RBPs [such as Insulin‑like growth factor 2 mRNA‑binding protein 1 (IGF2BP1) and YTH N6‑methyladenosine RNA binding protein F2 (YTHDF2)] in different GC subtypes and their clinical translatability remain unclear. Notably, RBPs show GC‑specific features (such as IGF2BP1/3 regulating metabolic coupling, YTHDF1 modulating dendritic cell recruitment) and clinical value [such as poly (rC)‑binding protein predicting peritoneal metastasis, Pumilio 1 guiding anti‑programmed cell death protein 1 therapy therapy]. This review highlights the GC‑specific mechanisms, controversial scientific issues and latest clinical translation progress of RBPs and proposes personalized treatment strategies based on the molecular characteristics of RBPs, aiming to provide a theoretical and practical basis for overcoming GC chemoresistance and molecular heterogeneity.