Identification of a TGF-β signaling-related gene signature for prediction of immunotherapy and targeted therapy for lung adenocarcinoma

World Journal of Surgical Oncology

Xiao-ping Lv¹  Liang Zhao²  Qing Bu²  Xue-xin Yan²  Ye Li²  Xin-yu Chen²  Qian Yu²  Xiao-hua Hu² 

[1] Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region;Department of Oncology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region;

关键词: TGF-β signaling;    Lung adenocarcinoma;    Risk model;    Prognosis;    Tumor microenvironment;    Immunotherapy;   

DOI  :  10.1186/s12957-022-02595-1

来源: DOAJ

【 摘 要 】

Abstract Background Transforming growth factor (TGF)-β signaling functions importantly in regulating tumor microenvironment (TME). This study developed a prognostic gene signature based on TGF-β signaling-related genes for predicting clinical outcome of patients with lung adenocarcinoma (LUAD). Methods TGF-β signaling-related genes came from The Molecular Signature Database (MSigDB). LUAD prognosis-related genes were screened from all the genes involved in TGF-β signaling using least absolute shrinkage and selection operator (LASSO) Cox regression analysis and then used to establish a risk score model for LUAD. ESTIMATE and CIBERSORT analyzed infiltration of immune cells in TME. Immunotherapy response was analyzed by the TIDE algorithm. Results A LUAD prognostic 5-gene signature was developed based on 54 TGF-β signaling-related genes. Prognosis of high-risk patients was significantly worse than low-risk patients. Both internal validation and external dataset validation confirmed a high precision of the risk model in predicting the clinical outcomes of LUAD patients. Multivariate Cox analysis demonstrated the model independence in OS prediction of LUAD. The risk model was significantly related to the infiltration of 9 kinds of immune cells, matrix, and immune components in TME. Low-risk patients tended to respond more actively to anti-PD-1 treatment, while high-risk patients were more sensitive to chemotherapy and targeted therapy. Conclusions The 5-gene signature based on TGF-β signaling-related genes showed potential for LUAD management.

【 授权许可】

Unknown