PLK1 is a Potential Prognostic Factor Associated With the Tumor Microenvironment During Lung Adenocarcinoma Progression

Abstract Background: Lung adenocarcinoma (LUAD) accounts for more than 40% of lung cancer cases worldwide, and the 5-year survival rate of LUAD patients is less than 10% due to a lack of reliable therapeutics. Here, we sought to identify a new therapeutic target for LUAD via bioinformatics analysis.Methods: Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was conducted for the differentially expressed genes (DEGs) identified in 551 samples from the Cancer Genome Atlas (TCGA) database. Gene set variation analysis (GSVA) and the CIBERSORT method were performed to estimate the expression profile of biological pathways and the population of tumor-infiltrating immune cells (TICs) in the TCGA dataset. DEGs were further analyzed by protein-protein interaction (PPI) network and Cox regression analyses, followed by RT-PCR and western blotting for confirmation. Results: Cell cycle was the only shared pathway identified by the KEGG and GSVA interaction analyses. Cell cycle score was positively associated with clinical characteristics (age, clinical stage, and metastasis) and negatively associated with overall survival in LUAD patients. PPI and Cox analyses identified PLK1 as a prognostic factor, which was positively correlated with clinical stage and negatively correlated with overall survival in LUAD patients. CIBERSORT analysis indicated that PLK1 expression was significantly positively correlated with CD8+ and activated memory CD4+ T cells, and negatively correlated with activated natural killer cells. Additionally, PLK1 overexpression resulted in increased immune cytotoxic metrics, such as cytolytic activity score, IFN-γ score, and IFN-γ level.Conclusions: PLK1 may be useful for survival estimation in LUAD patients due to its strong correlation with features of TICs in the tumor immune microenvironment.