Abstract
Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are m⁶A readers that stabilize target mRNAs by recognizing the GG(m⁶A)C sequence. While previous studies have explored the biological mechanisms of IGF2BPs in lung cancer, their prognostic value remains unclear. This study investigated the expression, molecular mechanisms, and prognostic significance of IGF2BPs in lung adenocarcinoma (LUAD) using TCGA and GEO datasets. IGF2BP1/2/3 were found to be highly expressed in LUAD, with high mRNA stability scores (RS) associated with shorter overall survival (OS) and linked to hypoxia, EMT, IL2-STAT5 signaling, immune suppression, and decreased gefitinib sensitivity. In cell-based experiments, siRNA knockdown of IGF2BPs in LUAD cell lines reduced TGF-β signaling pathway-related genes and inhibited cell proliferation. Our findings suggest that the IGF2BPs gene signature is a prognostic biomarker in LUAD, contributing to tumor progression, immune escape, and poor prognosis by activating specific pathways.