Harnessing natural killer cell-related genes for prognostic and therapeutic advances in lung adenocarcinoma: a predictive model for survival and immunotherapy outcomes.

Background: Lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer (NSCLC), is characterized by high mortality rates and complex immune evasion mechanisms. Natural killer (NK) cells play a crucial role in tumor immune surveillance, with their activity regulated by specific genes. Recently, biomarkers derived from NK cell-related genes have garnered significant attention for their potential in predicting cancer prognosis. This study aimed to evaluate the clinical utility of a prognostic model based on NK cell-related genes in patients with LUAD.

Methods: In this study, gene expression data and clinical information from LUAD patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and differentially expressed genes associated with natural killer cells (DENKCRGs) were identified. A prognostic risk score model was developed using least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis. The model's performance was subsequently validated through Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, enrichment analysis, and immune infiltration analysis. Additionally, its predictive capacity for immune therapy response and drug sensitivity was evaluated.

Results: A total of 493 LUAD patient datasets were retrieved from TCGA, 857 from the GEO database, and 244 NK cell-related genes were identified based on prior studies. The filtered data were then partitioned into training and testing sets. Through LASSO regression and Cox regression analysis, eight genes (PAK1, PLCG2, SHC3, SHC1, TOX, ARRB2, SERPINB4, and NLRC4) were identified as significantly associated with prognosis. A prognostic model based on these genes was developed, categorizing patients into high-risk and low-risk groups. Strong predictive performance was observed in the training set, testing set, and GEO dataset. Immune infiltration analysis revealed notable differences in immune cell distribution and immune response intensity between the high-risk and low-risk groups, with low-risk patients demonstrating greater responsiveness to immunotherapy. Furthermore, drug sensitivity analysis indicated that the high-risk group exhibited increased sensitivity to Axitinib, while the low-risk group showed higher responsiveness to drugs such as cisplatin.

Conclusions: The prognostic model developed in this study, based on NK cell-related genes, demonstrates considerable value in assessing the prognosis of LUAD. It not only serves as a predictor of patient survival but also provides a theoretical foundation for personalized immunotherapy and drug selection. Future research should focus on further validating the clinical applicability of this model and exploring its potential in the context of immunotherapy and targeted therapies.