Prognostic and Immunologic Significance of SH2B2 in Colon Adenocarcinoma and its Relationship to Proliferation, Migration, and Invasion.

Abstract

Background: SH2B adaptor protein 2 (SH2B2, also named APS) is an adaptor protein implicated in the modulation of insulin signaling pathways and glucose metabolism. Its role in colon adenocarcinoma (COAD) is unknown.

Methods: Data from The Cancer Genome Atlas and Gene Expression Omnibus database were utilized to assess SH2B2 expression and its clinical significance in COAD. We investigated the associations between SH2B2 expression with genomic instability, tumor mutational burden (TMB), DNA methylation, alternative splicing, immune infiltration, and drug sensitivity. A SH2B2 knockdown model was developed to examine its impact on COAD cellular functions.

Results: Highly expressed SH2B2 is associated with a poorer prognosis in COAD. SH2B2 expression in COAD is associated with copy number variations, microsatellite instability, methylation patterns, and alternative 5' splicing events, but not with TMB. SH2B2 is positively correlated with mostly immune cells and the expression of PD-1 and CTLA4. The IC50 values of ten drugs were significantly correlated with SH2B2 expression. BI-2536_1086 had a strong binding affinity with SH2B2. Furthermore, the knockdown of SH2B2 reduced the proliferation, migration, and invasion of COAD cells.

Conclusion: SH2B2 appears to act as an oncogene in COAD and may serve as a pivotal prognostic and therapeutic target, deserving further exploration.