Multi-omic analyses reveal PTPN6's impact on tumor immunity across various cancers

Protein Tyrosine Phosphatase Non-Receptor Type 6 (PTPN6) plays a crucial regulatory role in cellular processes and has been implicated in oncogenesis. This pan-cancer analysis aimed to elucidate PTPN6's involvement across various cancer types, with a particular emphasis on its association with tumor immunity. We analyzed PTPN6 expression data from open access databases using various statistical techniques, including survival analysis, genetic heterogeneity analysis, immune profiling, single-cell analysis, drug sensitivity analysis, and protein interaction analysis. We also conducted in vitro experiments utilizing colorectal cancer cell lines to validate PTPN6's functional role. PTPN6 exhibited distinct expression patterns across cancers, and its prognostic significance was apparent in several cancer types, particularly in glioblastoma, sarcoma, and melanoma. We observed correlations between PTPN6 and immune genes/cell infiltration in these cancers, suggesting a potential role in modulating the tumor immune microenvironment. Single-cell analysis revealed that PTPN6 is predominantly localized in macrophages, B cells, and dendritic cells within the tumor microenvironment, implying its involvement in regulating immune cell function. Enrichment analysis highlighted PTPN6's role in immune-related pathways. Drug sensitivity analysis identified specific drugs, including PAC-1, SNX-2112, BELINOSTAT, VORINOSTAT, TPCA-1, and PHA-893,888, whose efficacy may be influenced by PTPN6 expression. Knocking down PTPN6 expression inhibited the proliferation and migration of colorectal cancer cells in vitro, confirming its oncogenic role in this cancer type. This pan-cancer analysis establishes PTPN6's multifaceted influence on tumor immunity and its potential as a biomarker and therapeutic target.