Immune Landscape and Classification in Lung Adenocarcinoma Based on a Novel Cell Cycle Checkpoints Related Signature for Predicting Prognosis and Therapeutic Response

Frontiers in Genetics

Lijuan Tang¹  Zetian Gong²  Shiqin Li⁴  Sheng Ju⁵  Qifan Li⁵  Zhike Chen⁵  Jun Zhao⁵  Cheng Ding⁵  Jian Yang⁵  Hao Ding⁵  Yuan Cui⁵  Yu Li⁵  Li Wan⁶ 

[1] Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China;Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China;Department of Urinary Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China;Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China;Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, China;

关键词: lung adenocarcinoma;    cell cycle checkpoints;    prognostic signature;    tumour immune microenvironment;    therapeutic response;   

DOI  :  10.3389/fgene.2022.908104

来源: DOAJ

【 摘 要 】

Lung adenocarcinoma (LUAD) is one of the most common malignancies with the highest mortality globally, and it has a poor prognosis. Cell cycle checkpoints play a central role in the entire system of monitoring cell cycle processes, by regulating the signalling pathway of the cell cycle. Cell cycle checkpoints related genes (CCCRGs) have potential utility in predicting survival, and response to immunotherapies and chemotherapies. To examine this, based on CCCRGs, we identified two lung adenocarcinoma subtypes, called cluster1 and cluster2, by consensus clustering. Enrichment analysis revealed significant discrepancies between the two subtypes in gene sets associated with cell cycle activation and tumor progression. In addition, based on Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, we have developed and validated a cell cycle checkpoints-related risk signature to predict prognosis, tumour immune microenvironment: (TIME), immunotherapy and chemotherapy responses for lung adenocarcinoma patients. Results from calibration plot, decision curve analysis (DCA), and time-dependent receiver operating characteristic curve (ROC) revealed that combining age, gender, pathological stages, and risk score in lung adenocarcinoma patients allowed for a more accurate and predictive nomogram. The area under curve for lung adenocarcinoma patients with 1-, 3-, 5-, and 10-year overall survival was: 0.74, 0.73, 0.75, and 0.81, respectively. Taken together, our proposed 4-CCCRG signature can serve as a clinically useful indicator to help predict patients outcomes, and could provide important guidance for immunotherapies and chemotherapies decision for lung adenocarcinoma patients.

【 授权许可】

Unknown