The DDR-related gene signature with cell cycle checkpoint function predicts prognosis, immune activity, and chemoradiotherapy response in lung adenocarcinoma

Bibliographic Details
Title: The DDR-related gene signature with cell cycle checkpoint function predicts prognosis, immune activity, and chemoradiotherapy response in lung adenocarcinoma
Authors: Quan Li, Pan Zhang, Huixiao Hu, Hang Huang, Dong Pan, Guangyun Mao, Burong Hu
Source: Respiratory Research, Vol 23, Iss 1, Pp 1-17 (2022)
Publisher Information: BMC, 2022.
Publication Year: 2022
Collection: LCC:Diseases of the respiratory system
Subject Terms: Lung adenocarcinoma, Cancer prognosis, DNA damage repair, Cell cycle checkpoint, Gene signature, Diseases of the respiratory system, RC705-779
More Details: Abstract Background As a DNA surveillance mechanism, cell cycle checkpoint has recently been discovered to be closely associated with lung adenocarcinoma (LUAD) prognosis. It is also an essential link in the process of DNA damage repair (DDR) that confers resistance to radiotherapy. Whether genes that have both functions play a more crucial role in LUAD prognosis remains unclear. Methods In this study, DDR-related genes with cell cycle checkpoint function (DCGs) were selected to investigate their effects on the prognosis of LUAD. The TCGA-LUAD cohort and two GEO external validation cohorts (GSE31210 and GSE42171) were performed to construct a prognosis model based on the least absolute shrinkage and selection operator (LASSO) regression. Patients were divided into high-risk and low-risk groups based on the model. Subsequently, the multivariate COX regression was used to construct a prognostic nomogram. The ssGSEA, CIBERSORT algorithm, TIMER tool, CMap database, and IC50 of chemotherapeutic agents were used to analyze immune activity and responsiveness to chemoradiotherapy. Results 4 DCGs were selected as prognostic signatures, and patients in the high-risk group had a lower overall survival (OS). The lower infiltration levels of immune cells and the higher expression levels of immune checkpoints appeared in the high-risk group. The damage repair pathways were upregulated, and chemotherapeutic agent sensitivity was poor in the high-risk group. Conclusions The 4-DCGs signature prognosis model we constructed could predict the survival rate, immune activity, and chemoradiotherapy responsiveness of LUAD patients.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1465-993X
Relation: https://doaj.org/toc/1465-993X
DOI: 10.1186/s12931-022-02110-w
Access URL: https://doaj.org/article/0630163dc96d4a8cb8fd7ef8b9cb351f
Accession Number: edsdoj.0630163dc96d4a8cb8fd7ef8b9cb351f
Database: Directory of Open Access Journals
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More Details
ISSN:1465993X
DOI:10.1186/s12931-022-02110-w
Published in:Respiratory Research
Language:English