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

Protein Tyrosine Phosphatase Non-Receptor Type 6 (PTPN6) is a key regulator of cellular signaling and has been implicated in cancer development. This pan-cancer study investigated PTPN6′s role across multiple tumor types, with a focus on its connection to tumor immunity. We analyzed open-access datasets using a range of statistical methods, including survival analysis, genetic heterogeneity profiling, immune infiltration analysis, single-cell transcriptomics, drug sensitivity assessments, and protein interaction mapping. In vitro assays using colorectal cancer cell lines were also performed to validate functional findings.
PTPN6 displayed variable expression across cancer types and was significantly associated with prognosis in glioblastoma, sarcoma, and melanoma. Its expression correlated with immune-related genes and immune cell infiltration, suggesting a role in shaping the tumor immune microenvironment. Single-cell analysis showed that PTPN6 is primarily expressed in macrophages, B cells, and dendritic cells within tumors, supporting its involvement in immune regulation. Pathway enrichment analyses further linked PTPN6 to immune-related signaling.
Drug sensitivity analysis identified compounds—such as PAC-1, SNX-2112, BELINOSTAT, VORINOSTAT, TPCA-1, and PHA-893,888—whose efficacy may depend on PTPN6 expression. Functional experiments demonstrated that PTPN6 knockdown inhibited proliferation and migration of colorectal cancer cells, confirming its oncogenic role in this context.
Overall, this study highlights PTPN6 as a potential biomarker and therapeutic target due to its diverse roles in cancer progression and tumor immunity.