TPX2 plays a crucial role in regulating cancer progression and is a novel biomarker for predicting prognosis and response to immunotherapy

TPX2 is a mitotic spindle protein essential for cell division, with emerging but poorly defined roles in tumor biology. Although preliminary evidence links TPX2 to cancer progression, its pan-cancer function, prognostic significance, and relationship with the tumor immune microenvironment remain systematically uncharacterized. We executed a multi-omics workflow integrating transcriptomic and proteomic data from TCGA, GTEx, and HPA databases. Single-cell expression landscapes were characterized via the TISCH database, while the prognostic utility of TPX2 across 21 malignancies was evaluated through Kaplan-Meier and Cox regression analyses. Furthermore, the ESTIMATE algorithm, TIMER2.0, and TIP platforms were utilized to delineate immune infiltration patterns and anti-cancer immune cycles, alongside molecular docking to screen potential TPX2-targeting drugs. Computational findings were complemented by in vitro functional assays involving shRNA-mediated knockdown in A549, H1703, A498, and MCF-7 cell lines, as well as in vivo xenograft and metastasis models using A549 and A498 cells. TPX2 exhibited marked overexpression across various tumor tissues, with significant enrichment observed in malignant cells and proliferating T-cell populations. Elevated TPX2 expression served as a robust determinant of poor survival outcomes across 21 cancer types. Functional enrichment analyses (GSEA) implicated TPX2 in pathways governing cell cycle progression, invasion, and immune evasion. Strong correlations were identified between TPX2 abundance and immunosuppressive infiltration patterns, specifically high densities of MDSCs and Th2 cells. Clinically, high TPX2 expression was linked to diminished efficacy of anti-PD-1 immunotherapy in melanoma, lung squamous cell carcinoma, and renal cell carcinoma. Experimental validation confirmed that TPX2 depletion significantly attenuated cancer cell proliferation and migration in vitro, and suppressed tumor growth and pulmonary metastasis in lung and renal cancer models in vivo. TPX2 represents a promising pan-cancer biomarker for prognosis and immunotherapy response prediction. Its role in modulating the tumor immune microenvironment and malignant behavior supports its potential as a therapeutic target. Experimental validation confirms TPX2’s functional relevance, underscoring its translational value in cancer treatment.