Prognostic value and immune infiltration of a tumor microenvironment-related PTPN6 in metastatic melanoma

Background: Cutaneous melanoma is one of the most invasive and lethal skin malignant tumors. Compared to primary melanoma, metastatic melanoma (MM) presents poorer treatment outcomes and a higher mortality rate. The tumor microenvironment (TME) plays a critical role in MM progression and immunotherapy resistance. This study focuses on the role of the TME-related gene PTPN6 in the prognosis and immunotherapy response of MM.

Methods: This study analyzed the RNA-seq and clinical data of MM patients from public databases, employing the ESTIMATE algorithm and bioinformatics tools to identify differentially expressed genes in the TME. PTPN6 was identified as a prognostic biomarker. Its expression and function were validated using in vitro and in vivo experiments. The role of PTPN6 in immune cell infiltration and its association with the JAK2-STAT3 pathway and immunotherapy response were also evaluated.

Results: PTPN6 expression was significantly lower in MM and associated with poor prognosis. In vitro, Overexpression of PTPN6 inhibited proliferation, migration, and invasion, while knockdown reversed these effects. In vivo, PTPN6 overexpression reduced tumor growth. Mechanistically, PTPN6 suppressed JAK2-STAT3 signaling pathway activation. High PTPN6 expression was positively associated with immune cell infiltration, improved immunotherapy response, and reduced PD-L1 expression.

Conclusion: The gene PTPN6, associated with the tumor microenvironment, may serve as a promising prognostic biomarker and therapeutic target for MM.