Comprehensive analyses for the coagulation and macrophage-related genes to reveal their joint roles in the prognosis and immunotherapy of lung adenocarcinoma patients

PurposeThis study aims to explore novel biomarkers related to the coagulation process and tumor-associated macrophage (TAM) infiltration in lung adenocarcinoma (LUAD).MethodsThe macrophage M2-related genes were obtained by Weighted Gene Co-expression Network Analysis (WGCNA) in bulk RNA-seq data, wh...

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Main Authors: Zhuoqi Li, Zongxiu Yin, Zupeng Luan, Chi Zhang, Yuanyuan Wang, Kai Zhang, Feng Chen, Zhensong Yang, Yuan Tian
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1273422/full
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author Zhuoqi Li
Zhuoqi Li
Zongxiu Yin
Zupeng Luan
Chi Zhang
Yuanyuan Wang
Kai Zhang
Feng Chen
Zhensong Yang
Yuan Tian
Yuan Tian
author_facet Zhuoqi Li
Zhuoqi Li
Zongxiu Yin
Zupeng Luan
Chi Zhang
Yuanyuan Wang
Kai Zhang
Feng Chen
Zhensong Yang
Yuan Tian
Yuan Tian
author_sort Zhuoqi Li
collection DOAJ
description PurposeThis study aims to explore novel biomarkers related to the coagulation process and tumor-associated macrophage (TAM) infiltration in lung adenocarcinoma (LUAD).MethodsThe macrophage M2-related genes were obtained by Weighted Gene Co-expression Network Analysis (WGCNA) in bulk RNA-seq data, while the TAM marker genes were identified by analyzing the scRNA-seq data, and the coagulation-associated genes were obtained from MSigDB and KEGG databases. Survival analysis was performed for the intersectional genes. A risk score model was subsequently constructed based on the survival-related genes for prognosis prediction and validated in external datasets.ResultsIn total, 33 coagulation and macrophage-related (COMAR) genes were obtained, 19 of which were selected for the risk score model construction. Finally, 10 survival-associated genes (APOE, ARRB2, C1QB, F13A1, FCGR2A, FYN, ITGB2, MMP9, OLR1, and VSIG4) were involved in the COMAR risk score model. According to the risk score, patients were equally divided into low- and high-risk groups, and the prognosis of patients in the high-risk group was significantly worse than that in the low-risk group. The ROC curve indicated that the risk score model had high sensitivity and specificity, which was validated in multiple external datasets. Moreover, the model also had high efficacy in predicting the clinical outcomes of LUAD patients who received anti-PD-1/PD-L1 immunotherapy.ConclusionThe COMAR risk score model constructed in this study has excellent predictive value for the prognosis and immunotherapeutic clinical outcomes of patients with LUAD, which provides potential biomarkers for the treatment and prognostic prediction.
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spelling doaj.art-03d146f717214e2287512647dde1aa442023-10-31T09:48:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12734221273422Comprehensive analyses for the coagulation and macrophage-related genes to reveal their joint roles in the prognosis and immunotherapy of lung adenocarcinoma patientsZhuoqi Li0Zhuoqi Li1Zongxiu Yin2Zupeng Luan3Chi Zhang4Yuanyuan Wang5Kai Zhang6Feng Chen7Zhensong Yang8Yuan Tian9Yuan Tian10Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, ChinaRadiotherapy Department, Shandong Second Provincial General Hospital, Shandong University, Jinan, ChinaDepartment of Pulmonary and Critical Care Medicine, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Radiation Oncology, Jinan Third People’s Hospital, Jinan, ChinaDepartment of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Oncology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaGeneralsurgery Department, Wen-shang County People’s Hospital, Wenshang, ChinaDepartment of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Gastrointestinal Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, ChinaRadiotherapy Department, Shandong Second Provincial General Hospital, Shandong University, Jinan, ChinaPurposeThis study aims to explore novel biomarkers related to the coagulation process and tumor-associated macrophage (TAM) infiltration in lung adenocarcinoma (LUAD).MethodsThe macrophage M2-related genes were obtained by Weighted Gene Co-expression Network Analysis (WGCNA) in bulk RNA-seq data, while the TAM marker genes were identified by analyzing the scRNA-seq data, and the coagulation-associated genes were obtained from MSigDB and KEGG databases. Survival analysis was performed for the intersectional genes. A risk score model was subsequently constructed based on the survival-related genes for prognosis prediction and validated in external datasets.ResultsIn total, 33 coagulation and macrophage-related (COMAR) genes were obtained, 19 of which were selected for the risk score model construction. Finally, 10 survival-associated genes (APOE, ARRB2, C1QB, F13A1, FCGR2A, FYN, ITGB2, MMP9, OLR1, and VSIG4) were involved in the COMAR risk score model. According to the risk score, patients were equally divided into low- and high-risk groups, and the prognosis of patients in the high-risk group was significantly worse than that in the low-risk group. The ROC curve indicated that the risk score model had high sensitivity and specificity, which was validated in multiple external datasets. Moreover, the model also had high efficacy in predicting the clinical outcomes of LUAD patients who received anti-PD-1/PD-L1 immunotherapy.ConclusionThe COMAR risk score model constructed in this study has excellent predictive value for the prognosis and immunotherapeutic clinical outcomes of patients with LUAD, which provides potential biomarkers for the treatment and prognostic prediction.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1273422/fulllung adenocarcinomacoagulationtumor-associated macrophagerisk score modelprognosisimmunotherapy
spellingShingle Zhuoqi Li
Zhuoqi Li
Zongxiu Yin
Zupeng Luan
Chi Zhang
Yuanyuan Wang
Kai Zhang
Feng Chen
Zhensong Yang
Yuan Tian
Yuan Tian
Comprehensive analyses for the coagulation and macrophage-related genes to reveal their joint roles in the prognosis and immunotherapy of lung adenocarcinoma patients
Frontiers in Immunology
lung adenocarcinoma
coagulation
tumor-associated macrophage
risk score model
prognosis
immunotherapy
title Comprehensive analyses for the coagulation and macrophage-related genes to reveal their joint roles in the prognosis and immunotherapy of lung adenocarcinoma patients
title_full Comprehensive analyses for the coagulation and macrophage-related genes to reveal their joint roles in the prognosis and immunotherapy of lung adenocarcinoma patients
title_fullStr Comprehensive analyses for the coagulation and macrophage-related genes to reveal their joint roles in the prognosis and immunotherapy of lung adenocarcinoma patients
title_full_unstemmed Comprehensive analyses for the coagulation and macrophage-related genes to reveal their joint roles in the prognosis and immunotherapy of lung adenocarcinoma patients
title_short Comprehensive analyses for the coagulation and macrophage-related genes to reveal their joint roles in the prognosis and immunotherapy of lung adenocarcinoma patients
title_sort comprehensive analyses for the coagulation and macrophage related genes to reveal their joint roles in the prognosis and immunotherapy of lung adenocarcinoma patients
topic lung adenocarcinoma
coagulation
tumor-associated macrophage
risk score model
prognosis
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1273422/full
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