SH3BGRL3 is a pancancer prognostic and immunological biomarker.

Background

SH3 Domain Binding Glutamate Rich Protein Like 3 (SH3BGRL3) plays a crucial part in regulating tumor necrosis factor (TNF)-induced effects and was involved in the onset and progression of various cancers. However, its role at pan-cancer level remains unclear.

Methods

Firstly, SH3BGRL3 expression and its correlation with patients' survival, and other clinical variables were explored in our clinical cohort of 370 kidney neoplasm patients. Subsequently, differential expression analysis, competing endogenous RNA and protein-protein interaction network analysis, correlation analysis with clinical characteristics, tumor purity, gene alteration, immune landscape and signaling pathways were performed to evaluate the role of SH3BGRL3 in pan-cancer. Drug sensitivity analysis, molecular docking and in vitro experiments were also conducted to explore its possible pharmaceutical significance.

Results

In our clinical cohort of kidney neoplasms, SH3BGRL3 was downregulated in tumor tissues (p < 0.001). Higher tumor SH3BGRL3 was linked to decreased overall survival (p = 0.022), advanced stages and was an independent risk factor for progression-free survival (hazard ratio = 2.11, 95%confidence interval = 1.05-4.2, p = 0.037). Further pan-cancer analysis revealed that SH3BGRL3 expression was upregulated in most tumors, and correlated with unfavorable outcomes and advanced tumor stages of various cancers. It was also associated with tumor purity, tumor genomics, tumor immunity, pathway enrichment, and drug sensitivity at pan-cancer level. Dasatinib was found to effectively suppress SH3BGRL3.

Conclusions

SH3BGRL3 was an independent prognostic factor in our kidney neoplasm cohort. At the pan-cancer level, it served as a promising prognostic and immunological biomarker exhibiting cancer-type-specific variations.