Construction and clinical significance of prognostic risk markers based on cancer driver genes in lung adenocarcinoma

Abstract

Background

Cancer driver genes (CDGs) have been reported as key factors influencing the progression of lung adenocarcinoma (LUAD). However, the role of CDGs in LUAD prognosis has not been fully elucidated.

Methods

LUAD transcriptome data and CDG-related data were obtained from public databases and literature. Differentially expressed CDGs (DE-CDGs) greatly associated with LUAD survival (P < 0.05) were identified to establish a prognostic model. In addition, immune analysis of high-risk (HR) and low-risk (LR) groups was conducted by utilizing the CIBERSORT and single sample gene set enrichment analysis (ssGSEA) algorithms to assess immune differences. Subsequently, mutation analysis was conducted using maftools. Finally, candidate drugs were identified using the CellMiner database.

Results

40 DE-CDGs significantly associated with LUAD survival and 11 DE-CDGs associated with prognosis were identified through screening. Regression analysis revealed that risk score can independently predict LUAD prognosis (P < 0.05). Immune landscape analysis revealed that compared to the HR group, the LR group had higher immune scores and high infiltration of various immune cells such as follicular helper B cells and T cells. Mutation landscape analysis demonstrated that missense mutation was the most common mutation type in both risk groups. Drug prediction analysis revealed strong correlations of fulvestrant, S-63845, sapacitabine, lomustine, BLU-667, SR16157, motesanib, AZD-9496, XK-469, dimethylfasudil, P-529, and imatinib with the model genes, suggesting their potential as candidate drugs targeting the model genes.

Conclusion

This study identified 11 effective biomarkers, DE-CDGs, which can predict LUAD prognosis and explored the biological significance of CDGs in LUAD prognosis, immunotherapy, and treatment.