Development of a novel centrosome-related risk signature to predict prognosis and treatment response in lung adenocarcinoma

Abstract

Abstract Background Abnormalities of centrosomes, the major microtubular organizing centers of animal cells and regulators of cell cycle progression, usually accelerate tumor progression, but their prognostic value in lung adenocarcinoma (LUAD) remains insufficiently explored. Methods We collected centrosome genes from the literature and identified LUAD-specific centrosome-related genes (CRGs) using the single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA). Univariate Cox was performed to screen prognostic CRGs. Consistent clustering was performed to classify LUAD patients into two subgroups, and centrosome-related risk score signatures were constructed by Lasso and multivariate Cox regression to predict overall survival (OS). We further explored the correlation between CRS and patient prognosis, clinical manifestations, mutation status, tumor microenvironment, and response to different treatments. Results We constructed centrosome-associated prognostic features and verified that CRS could effectively predict 1-, 3-, and 5-year survival in LUAD patients. In addition, patients in the high-risk group exhibited elevated tumor mutational loads and reduced levels of immune infiltration, particularly of T and B cells. Patients in the high-risk group were resistant to immunotherapy and sensitive to 5-fluoropyrimidine and gefitinib. The key gene spermine synthase (SRM) is highly expressed at the mRNA and protein levels in LUAD. Discussion Our work develops a novel centrosome-related prognostic signature that accurately predicts OS in LUAD and can assist in clinical diagnosis and treatment.

Keywords

• Lung adenocarcinoma
• Centrosome
• CRS
• Prognostic model
• Tumor microenvironment