A novel signature predicts prognosis and immunotherapy in lung adenocarcinoma based on cancer-associated fibroblasts

Frontiers in Immunology

Immunology

Hao Chi¹  Zhijia Xia²  Huabao Cai³  Xiao Zhang⁴  Haoran Lin⁴  Qianhe Ren⁴  Yue Yu⁴  Pengpeng Zhang⁴  Yanlong Feng⁴ 

[1] Clinical Medical College, Southwest Medical University, Luzhou, China;Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, Munich, Germany;Department of Neurosurgery, First Affiliated Hospital of Anhui Medical University, Hefei, China;Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;

关键词: lung adenocarcinoma;    fibroblast;    prognosis;    tumor immune microenvironment;    immunotherapy;   

DOI  :  10.3389/fimmu.2023.1201573

 received in 2023-04-06, accepted in 2023-05-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundExtensive research has established the significant correlations between cancer-associated fibroblasts (CAFs) and various stages of cancer development, including initiation, angiogenesis, progression, and resistance to therapy. In this study, we aimed to investigate the characteristics of CAFs in lung adenocarcinoma (LUAD) and develop a risk signature to predict the prognosis of patients with LUAD.MethodsWe obtained single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from the public database. The Seurat R package was used to process the scRNA-seq data and identify CAF clusters based on several biomarkers. CAF-related prognostic genes were further identified using univariate Cox regression analysis. To reduce the number of genes, Lasso regression was performed, and a risk signature was established. A novel nomogram that incorporated the risk signature and clinicopathological features was developed to predict the clinical applicability of the model. Additionally, we conducted immune landscape and immunotherapy responsiveness analyses. Finally, we performed in vitro experiments to verify the functions of EXO1 in LUAD.ResultsWe identified 5 CAF clusters in LUAD using scRNA-seq data, of which 3 clusters were significantly associated with prognosis in LUAD. A total of 492 genes were found to be significantly linked to CAF clusters from 1731 DEGs and were used to construct a risk signature. Moreover, our immune landscape exploration revealed that the risk signature was significantly related to immune scores, and its ability to predict responsiveness to immunotherapy was confirmed. Furthermore, a novel nomogram incorporating the risk signature and clinicopathological features showed excellent clinical applicability. Finally, we verified the functions of EXP1 in LUAD through in vitro experiments.ConclusionsThe risk signature has proven to be an excellent predictor of LUAD prognosis, stratifying patients more appropriately and precisely predicting immunotherapy responsiveness. The comprehensive characterization of LUAD based on the CAF signature can predict the response of LUAD to immunotherapy, thus offering fresh perspectives into the management of LUAD patients. Our study ultimately confirms the role of EXP1 in facilitating the invasion and growth of tumor cells in LUAD. Nevertheless, further validation can be achieved by conducting in vivo experiments.

【 授权许可】

Unknown   
Copyright © 2023 Ren, Zhang, Lin, Feng, Chi, Zhang, Xia, Cai and Yu