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pmid:35840978
The DDR-related gene signature with cell cycle checkpoint function predicts prognosis, immune activity, and chemoradiotherapy response in lung adenocarcinoma.
Quan Li · Pan Zhang · Huixiao Hu · Hang Huang · Dong Pan · Guangyun Mao · Burong Hu
Respiratory research · 2022 doi:10.1186/s12931-022-02110-w
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Complete file
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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.\nMETHODS: 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.\nRESULTS: 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.\nCONCLUSIONS: The 4-DCGs signature prognosis model we constructed could predict the survival rate, immune activity, and chemoradiotherapy responsiveness of LUAD patients.", "claims": [{"id": "claim-method", "statement": "Subsequently, the least absolute shrink-age and selection operator (LASSO) regression model was used to prevent overfitting, selecting the best candidate genes into the prognosis model by using the R package “glmnet”.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35840978", "locator": "sections[8] \"Establishment and validation of the DCGs prognostic model\" paragraph 4", "quote": "Subsequently, the least absolute shrink-age and selection operator (LASSO) regression model was used to prevent overfitting, selecting the best candidate genes into the prognosis model by using the R package “glmnet”."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Public datasets this study used can be found in The Cancer Genome Atlas (https://portal.gdc.cancer.gov/) and the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/). 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