A novel Lactylation-related gene signature to predict prognosis and treatment response in lung adenocarcinoma

Zhang Hongyi Yihao Liu Xuanguang Li Chen Ding Chunqiu Xia Hua Huang HONGYU LIU Jun Chen ^*

• Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China

Background: Lactylation, a novel post-translational modification, has emerged as a critical regulatory mechanism in various biological processes, including tumor progression. However, its role and associated gene signatures in lung adenocarcinoma (LUAD) remain unclear.Methods: RNA sequencing data of LUAD patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.Unsupervised clustering was used to identify lactylation-related genes. A risk prognostic model was constructed using least absolute shrinkage and selection operator regression analysis and subsequently validated. A nomogram was then employed to optimize the clinical applicability of the risk score. Additionally, various algorithms were used to explore the relationship between the risk score and immune infiltration levels, with model genes analyzed based on single-cell sequencing. The effects of RCCD1 knockdown on LUAD cell proliferation and migration were evaluated through CCK8 and transwell assays.Results: Higher risk scores were associated with poorer overall survival prognosis.Immune analysis revealed that the risk score may play a role in regulating the tumor microenvironment. Additionally, these risk scores were found to be associated with chemotherapy drug sensitivity. A series of experiments further demonstrated that RCCD1 promotes LUAD cell proliferation and migration in vitro.Conclusion: This study highlights the critical role of lactylation-related gene signatures in LUAD and their association with immune cell infiltration, providing insights into potential therapeutic targets and biomarkers for clinical application.