PMEPA1 in laryngeal squamous cell carcinoma: Prognostic value, immune associations, and predicted drug sensitivity

Reliable prognostic biomarkers for laryngeal squamous cell carcinoma (LSCC) remain limited. This study evaluated prostate transmembrane protein androgen induced 1 (PMEPA1) expression, prognostic significance, functional effects, and immune and drug sensitivity associations. Transcriptomic and clinical data from The Cancer Genome Atlas and Gene Expression Omnibus were analyzed using Kaplan-Meier analysis, Cox regression, functional enrichment, immune deconvolution, and drug sensitivity prediction. Expression and knockdown effects were assessed using quantitative reverse transcription polymerase chain reaction, western blotting, cell viability assays, and Transwell assays. PMEPA1 was upregulated in tumors and cancer cell lines. Higher expression was associated with poorer overall survival in two cohorts and remained significant after multivariable adjustment in the discovery cohort. Areas under the receiver operating characteristic curve (AUCs) for tumor-normal discrimination ranged from 0.835 to 0.944; nomogram AUCs were 0.766, 0.772, and 0.809 at 1, 3, and 5 years. Enrichment analyses highlighted extracellular matrix organization. PMEPA1 knockdown reduced viability, migration, and invasion in one LSCC cell line. Computational analyses linked higher expression to greater proportions of unpolarized (M0) and alternatively activated (M2) macrophages, lower cluster of differentiation 8-positive (CD8+) T-cell proportions, and higher stromal and immune exclusion scores. Expression correlated positively with predicted half-maximal inhibitory concentrations (IC₅₀) of entinostat and vorinostat and negatively with those of dasatinib and AZD1332. PMEPA1 is a candidate prognostic biomarker with functional relevance in LSCC; its immune and drug sensitivity associations require experimental and clinical validation.