Multidimensional analysis on the potential of cell cycle-related gene STMN1 as a tumor biomarker

STMN1 is a critical microtubule-destabilizing protein that controls cell division and cytoskeleton dynamics and participates in tumor initiation and progression. Nevertheless, systematic pan-cancer research on its function, clinical significance and therapeutic value is still lacking. Herein, multi-omics data and bioinformatics methods were adopted to comprehensively analyze pan-cancer expression, genomic variation, prognostic significance and potential mechanisms of STMN1, combined with in vitro functional verification in hepatocellular carcinoma (HCC). STMN1 was markedly overexpressed in most malignancies and closely linked to advanced tumor staging; frequent gene mutations and copy number amplification elevated its transcription and predicted unfavorable prognosis in multiple tumors. High STMN1 expression indicated poor survival in eight cancers yet favorable prognosis in thymoma and neuroblastoma. STMN1 was closely associated with cancer stemness and multiple RNA modifications, and its co-expressed genes were enriched in cell cycle and DNA replication pathways. Its correlations with immune infiltration, tumor mutational burden, microsatellite instability and immune checkpoints varied among cancers, which helped distinguish immunotherapy responders. High STMN1 altered sensitivity to multiple targeted drugs. In HCC, STMN1 upregulation was verified in tumor tissues and correlated with advanced clinicopathological features; it independently predicted poor overall survival and was incorporated into a high-precision nomogram. Cell experiments confirmed that STMN1 knockdown restrained HCC proliferation and metastasis by regulating cell cycle and EMT pathways. Collectively, STMN1 acts as a promising pan-cancer diagnostic and prognostic biomarker as well as an immunotherapy predictor, laying a foundation for tumor precise diagnosis and individualized therapy.