Set binding factor 1 (SBF1/MTMR5) as a potential novel target in colorectal cancer: an exploratory immunohistochemical and bioinformatics study

Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality worldwide, and dysregulation of phosphoinositides signaling pathways plays a critical role in its pathogenesis. The involvement of Set Binding Factor 1 (SBF1; MTMR5), a pseudophosphatase of the myotubularin family in CRC, remains unexplored. This study compiled experimental and bioinformatics approaches to investigate the expression and potential relevance of SBF1 in CRC. Immunohistochemical analysis was performed on CRC tissue specimens and corresponding normal adjacent tissues (NAT), with estimation of SBF1 staining followed by statistical comparison. In parallel, bioinformatics assessed gene ontology and protein-protein interactions, and open CRC datasets were analyzed to assess SBF1 alterations, expression profiles, and survival associations. The results demonstrated a significant overexpression of SBF1 in CRC tissues compared with NAT. Bioinformatics revealed SBF1 as a partner within a functional network enriched in phosphoinositide metabolism. Bioinformatics identified SBF1 genetic alterations in approximately 5% of cases, and survival analysis indicated that wild-type SBF1 could be an unfavorable prognostic marker, as reflected by hazard assessment. Collectively, these findings provided the first experimental evidence that SBF1 is overexpressed in CRC and suggest that it may represent an unrecognized component of phosphoinositide related pathways involved in colorectal tumorigenesis.