IGF2BP3 as a Novel Prognostic Biomarker and Therapeutic Target in Lung Adenocarcinoma

RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show...

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Main Authors: Feiming Hu, Chenchen Hu, Yuanli He, Lin Guo, Yuanjie Sun, Chenying Han, Xiyang Zhang, Junyi Ren, Jinduo Han, Jing Wang, Junqi Zhang, Yubo Sun, Sirui Cai, Dongbo Jiang, Kun Yang, Shuya Yang
Format: Article
Language:English
Published: MDPI AG 2025-08-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/15/1222
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Summary:RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show IGF2BP3 was significantly upregulated in LUAD tissues and associated with advanced-stage, larger tumors, lymph node metastasis, and poor prognosis. A prognostic nomogram confirmed its independent predictive value. Functionally, IGF2BP3 knockdown suppressed proliferation, and induced G2/M arrest and apoptosis. GSEA linked high IGF2BP3 to cell cycle activation and low expression to metabolic pathways. Notably, high IGF2BP3 correlated with immune evasion markers (downregulated CD4+ effector T cells, upregulated Th2 cells), while TIDE analysis suggested a better immunotherapy response in low-expressing patients. Drug screening identified BI-2536 as a potential therapy for low-IGF2BP3 cases, supported by strong molecular docking affinity (−7.55 kcal/mol). These findings establish IGF2BP3 as a key driver of LUAD progression and a promising target for immunotherapy and precision medicine.
ISSN:2073-4409