PLK1 overexpression as a dual-role biomarker and therapeutic vulnerability in pulmonary adenocarcinoma.

BACKGROUND: PLK1 is associated with various malignant tumors, but its correlation with lung adenocarcinoma (LUAD) remains unclear. This research seeks to explore the differences in PLK1 expression in LUAD and evaluate the relationship between PLK1 expression and the outcomes for LUAD patients. METHODS: Information on LUAD patients was sourced from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Genotype-Tissue Expression (GTEx). The XianTao Academic Online Platform was employed for systematic analysis of PLK1, including: (1) Wilcoxon rank-sum test to compare PLK1 expression between LUAD and normal tissues; (2) logistic regression analysis evaluating PLK1-clinicopathological feature relationships; (3) Kaplan-Meier and COX regression analyses assessing prognostic significance; (4) nomogram construction for survival prediction. Immunohistochemical (IHC) staining results from the Human Protein Atlas (HPA) validated PLK1 protein expression. Functional characterization using the XianTao platform included: (1) Analysis of PLK1-coexpressed genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways; (2) single-sample gene set enrichment analysis (ssGSEA) to measure immune cell infiltration in tumors with high PLK1 expression. In vitro validation included: (1) cell proliferation assessment (CCK-8 and colony formation assays); (2) apoptosis detection via Annexin V/PI staining; (3) cell cycle analysis by PI staining flow cytometry; (4) cell cycle-related protein expression evaluation using Western blotting (Cyclin B1, CDK1). RESULTS: PLK1 expression was significantly elevated in LUAD tumor tissues compared to adjacent normal samples across multiple cohorts. Elevated PLK1 expression was strongly associated with advanced clinicopathological stages (tumor/node/metastasis (T/N/M)) and poorer overall survival. Functional enrichment analysis revealed that genes co-expressed with PLK1 were predominantly involved in cell cycle regulatory pathways. Furthermore, transcriptomic profiling indicated a significant correlation between high PLK1 expression and an immunosuppressive tumor microenvironment. Experimental validation in A549 cells demonstrated that pharmacological inhibition of PLK1 (via GSK461364) effectively suppressed cell proliferation, induced G2/M phase arrest, promoted apoptosis, and led to the accumulation of Cyclin B1 and CDK1 proteins. CONCLUSION: PLK1 overexpression signifies aggressive disease and poor prognosis in LUAD, mechanistically linked to cell cycle dysregulation and an immunosuppressive microenvironment. Our findings nominate PLK1 as a promising therapeutic target and biomarker, warranting further investigation into PLK1-directed therapies.