Pan-cancer analysis of PDZK1IP1 reveals its role in tumorigenesis and tumor immunity: focused validation in thyroid carcinoma

BACKGROUND: PDZK1IP1 is a membrane protein linked to inflammation and cancer, but its role in the tumor immune microenvironment is poorly understood. This study systematically investigated the oncogenic and immunological functions of PDZK1IP1 via a pan-cancer analysis, with experimental validation in thyroid carcinoma (THCA). METHODS: We conducted a comprehensive bioinformatic analysis of PDZK1IP1 using publicly available platforms (TIMER, GEPIA, c-BioPortal, TISIDB, SangerBox) to examine its expression, diagnostic potential, prognostic relevance, and correlation with key immune features, including immune checkpoint genes, tumor mutational burden, neoantigen load, tumor stemness, and immune cell infiltration. Findings were validated in a THCA cohort using RT-PCR and immunohistochemistry. RESULTS: PDZK1IP1 was overexpressed in multiple cancers, showed significant diagnostic potential, and was a context-dependent prognostic marker, correlating with poor relapse-free survival in THCA. Its expression was strongly associated with tumor mutational burden, neoantigen load, tumor stemness, and the infiltration of various immune cells (particularly neutrophils) across multiple cancers. These findings were corroborated in THCA, in which PDZK1IP1 expression correlated with the infiltration of five distinct immune cell types. Functional enrichment analysis confirmed an association with neutrophil activation pathways. CONCLUSIONS: Our study identified PDZK1IP1 with dual functions, acting as both an oncogene and a modulator of the tumor immune microenvironment. These findings highlight its potential as a prognostic biomarker and therapeutic target for immunotherapy, especially in THCA.