Comprehensive pan-cancer analysis reveals SH3GLB1 is a novel prognostic biomarker with immunomodulatory potential

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BACKGROUND: Cancer continues to represent a significant global health challenge, underscoring the urgent need for novel biomarkers to enhance early diagnosis and prognosis prediction. SH3 domain-containing GRB2-like B1 (SH3GLB1), also known as Bax interaction factor 1 (BIF-1), is a key regulator of apoptosis, autophagy, and endocytosis. However, its role across various cancer types remains insufficiently characterized. METHODS: We performed an integrated multi-omics analysi to assess the diagnostic and prognostic potential of SH3GLB1 across 33 cancer types, encompassing expression profiling at both mRNA and protein levels, genomic alterations, interactions with the immune microenvironment, and functional enrichment pathways. The finding was validated in Colorectal Cancer (CRC), both in vitro and in vivo. RESULTS: SH3GLB1 expression was significantly downregulated in the majority of tumor types examined, at both mRNA and protein levels. Low SH3GLB1 expression was associated with poorer overall survival in CRC and several other cancers. Besides, SH3GLB1 was correlated with immune-inflamed tumor microenvironments, characterized by increased infiltration of CD8 + T cells and dendritic cells. Functional analyses revealed that SH3GLB1 loss activated RAS-MAPK and EMT signaling pathways, and experimental models confirmed its role in promoting CRC cell proliferation, migration in vitro, and tumor growth in vivo. CONCLUSION: SH3GLB1 exhibits significant diversity and complexity in its tumor-suppressive functions, highlighting its potential as a promising biomarker and therapeutic target for improving the efficacy of cancer treatments.

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