PLK1 is a prognostic marker that inhibits immune infiltration in lung adenocarcinoma through necroptosis

Abstract

Abstract Background Polo-like kinase 1 (PLK1) is essential for cell mitosis division and has been associated with necroptosis. Although PLK1 and necroptosis are implicated in a variety of cancers, their function in lung adenocarcinoma (LUAD) is still not fully understood. METHODS The differential expression of PLK1 in LUAD was investigated utilizing Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, and its prognostic significance was determined using the Kaplan-Meier test. Potential signaling pathways and biological activities were investigated using functional analysis. The overall survival (OS) of LUAD patients at 1, 3, and 5 years was predicted using multivariate Cox regression and validated using independent datasets. PLK1 was studied for its connection to immunological infiltration. Finally, the PLK1 impact on proliferation and apoptosis of LUAD cells was detected by overexpression and silencing PLK1. PLK1 impact on LUAD cell proliferation was verified by Western blot and in a xenograft model. Result PLK1 overexpression in LUAD was associated with TNM pathological staging, and residual tumor/smoking. High PLK1 expression correlated with lower OS, DFS, and DFI. PLK1 was determined as a significant predictor of LUAD by multivariate Cox regression. Functional analyses indicated PLK1 function was related to cell mitosis, neurotransmitter transmission and drug metabolism. Immune infiltration analysis showed that PLK1 was upregulated in cold tumors and inversely correlated to T cells, B cells and CD8+ T cells. Cellular assays demonstrated that PLK1 was significantly overexpressed in A549 and NCI-H1299 cell lines. Silencing PLK1 reduced proliferation and significantly increased LUAD cell apoptosis. Western Blot showed that the expression of necroptosis-related pathway proteins RIPK3, RIPK1, and MLKL was significantly increased after silencing PLK1. Finally, silencing PLK1 decreased LUAD cell proliferation in the xenograft model. Conclusion PLK1 may be a prognostic biomarker and suppresses LUAD immune infiltration by inhibiting necroptosis to promote LUAD cell proliferation.