Pan-Cancer Analysis of hnRNPAB: Implications in Tumor Progression, Prognosis, and Immune Microenvironment Modulation

Background: hnRNPAB, a member of the hnRNP protein family, is involved in mRNA cytoplasmic localization, transport, and the regulation of transcription, metabolism, and splicing. It is associated with malignant progression and metastasis in liver cancer and lung adenocarcinoma. However, a systematic pan-cancer analysis exploring its role in diagnosis, prognosis, and immune prediction is lacking. Methods: This study evaluated hnRNPAB expression across 33 cancers and its association with immune infiltration using UCSC Xena, TIMER, GEPIA, BioGPS, and ARCHS4 databases. Methylation levels were analyzed using UALCAN and MethSurv. Survival analysis was performed with GEPIA and MethSurv platforms, and mutation analysis was conducted via cBioPortal. Protein interaction networks were constructed using STRING and Cytoscape, and functional enrichment analyses were performed with KEGG and GSVA. Immune infiltration was assessed using TIMER, CIBERSORT, and quanTIseq, and the relationship between hnRNPAB and cancer-associated fibroblasts (CAFs) was analyzed using TIMER2.0. Results: hnRNPAB was significantly overexpressed in various cancers, with high expression correlating with poor prognosis. Mutation analysis revealed that amplification mutations of hnRNPAB were associated with worse survival rates. Low methylation of hnRNPAB was linked to cancer progression. Additionally, hnRNPAB was involved in cell cycle regulation, mTORC1, and PI3K-AKT signaling pathways. Immune cell infiltration analysis demonstrated a significant association between hnRNPAB and CAF infiltration, affecting immune therapy outcomes. Conclusion: This study highlights the association between hnRNPAB overexpression and poor prognosis across multiple cancers, particularly in kidney and liver cancers. hnRNPAB promotes tumor growth and metastasis by regulating immune cell infiltration and CAF activity. The study also explores its mutations and methylation status, suggesting its potential as a therapeutic target or biomarker in cancer metabolism reprogramming and immune evasion.