Identification and validation of a novel cuproptosis-related stemness signature to predict prognosis and immune landscape in lung adenocarcinoma by integrating single-cell and bulk RNA-sequencing

Frontiers in Immunology

Immunology

Kaile Liu¹  Zhongqi Wang¹  Lu Yang¹  Jia Yang¹  Haibin Deng¹  Junqing Ji¹  Jingru Qin¹ 

[1] Department of Medical Oncology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China;

关键词: cuproptosis-related stemness genes (CRSGs);    prognostic signature;    immune landscape;    single-cell sequencing;    lung adenocarcinoma;    cancer stem cells;   

DOI  :  10.3389/fimmu.2023.1174762

 received in 2023-02-27, accepted in 2023-05-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundCancer stem cells (CSCs) play vital roles in lung adenocarcinoma (LUAD) recurrence, metastasis, and drug resistance. Cuproptosis has provided a novel insight into the treatment of lung CSCs. However, there is a lack of knowledge regarding the cuproptosis-related genes combined with the stemness signature and their roles in the prognosis and immune landscape of LUAD.MethodsCuproptosis-related stemness genes (CRSGs) were identified by integrating single-cell and bulk RNA-sequencing data in LUAD patients. Subsequently, cuproptosis-related stemness subtypes were classified using consensus clustering analysis, and a prognostic signature was constructed by univariate and least absolute shrinkage operator (LASSO) Cox regression. The association between signature with immune infiltration, immunotherapy, and stemness features was also investigated. Finally, the expression of CRSGs and the functional roles of target gene were validated in vitro.ResultsWe identified six CRSGs that were mainly expressed in epithelial and myeloid cells. Three distinct cuproptosis-related stemness subtypes were identified and associated with the immune infiltration and immunotherapy response. Furthermore, a prognostic signature was constructed to predict the overall survival (OS) of LUAD patients based on eight differently expressed genes (DEGs) with cuproptosis-related stemness signature (KLF4, SCGB3A1, COL1A1, SPP1, C4BPA, TSPAN7, CAV2, and CTHRC1) and confirmed in validation cohorts. We also developed an accurate nomogram to improve clinical applicability. Patients in the high-risk group showed worse OS with lower levels of immune cell infiltration and higher stemness features. Ultimately, further cellular experiments were performed to verify the expression of CRSGs and prognostic DEGs and demonstrate that SPP1 could affect the proliferation, migration, and stemness of LUAD cells.ConclusionThis study developed a novel cuproptosis-related stemness signature that can be used to predict the prognosis and immune landscape of LUAD patients, and provided potential therapeutic targets for lung CSCs in the future.

【 授权许可】

Unknown   
Copyright © 2023 Yang, Liu, Yang, Ji, Qin, Deng and Wang