Construction and validation of a 15-gene ferroptosis signature in lung adenocarcinoma

Background Ferroptosis is a novel form of programmed cell death characterized by the excessive accumulation of intracellular iron and an increase in reactive oxygen species. Emerging studies have shown that ferroptosis plays a vital role in the progression of lung adenocarcinoma, but the effect of f...

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Main Authors: Guangxu Tu, Weilin Peng, Qidong Cai, Zhenyu Zhao, Xiong Peng, Boxue He, Pengfei Zhang, Shuai Shi, Yongguang Tao, Xiang Wang
Format: Article
Language:English
Published: PeerJ Inc. 2021-07-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/11687.pdf
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author Guangxu Tu
Weilin Peng
Qidong Cai
Zhenyu Zhao
Xiong Peng
Boxue He
Pengfei Zhang
Shuai Shi
Yongguang Tao
Xiang Wang
author_facet Guangxu Tu
Weilin Peng
Qidong Cai
Zhenyu Zhao
Xiong Peng
Boxue He
Pengfei Zhang
Shuai Shi
Yongguang Tao
Xiang Wang
author_sort Guangxu Tu
collection DOAJ
description Background Ferroptosis is a novel form of programmed cell death characterized by the excessive accumulation of intracellular iron and an increase in reactive oxygen species. Emerging studies have shown that ferroptosis plays a vital role in the progression of lung adenocarcinoma, but the effect of ferroptosis-related genes on prognosis has been poorly studied. The purpose of this study was to explore the prognostic value of ferroptosis-related genes. Methods Lung adenocarcinoma samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to establish a predictive signature for risk stratification. Kaplan–Meier (K–M) survival analysis and receiver operating characteristic (ROC) curve analysis were conducted to evaluate the signature. We further explored the potential correlation between the risk score model and tumor immune status. Results A 15-gene ferroptosis signature was constructed to classify patients into different risk groups. The overall survival (OS) of patients in the high-risk group was significantly shorter than that of patients in the low-risk group. The signature could predict OS independent of other risk factors. Single-sample gene set enrichment analysis (ssGSEA) identified the difference in immune status between the two groups. Patients in the high-risk group had stronger immune suppression, especially in the antigen presentation process. Conclusions The 15-gene ferroptosis signature identified in this study could be a potential biomarker for prognosis prediction in lung adenocarcinoma. Targeting ferroptosis might be a promising therapeutic alternative for lung adenocarcinoma.
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spelling doaj.art-35716a76ed9f4fb5b5b3ff114adac41f2023-12-03T11:05:31ZengPeerJ Inc.PeerJ2167-83592021-07-019e1168710.7717/peerj.11687Construction and validation of a 15-gene ferroptosis signature in lung adenocarcinomaGuangxu Tu0Weilin Peng1Qidong Cai2Zhenyu Zhao3Xiong Peng4Boxue He5Pengfei Zhang6Shuai Shi7Yongguang Tao8Xiang Wang9Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaKey Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaBackground Ferroptosis is a novel form of programmed cell death characterized by the excessive accumulation of intracellular iron and an increase in reactive oxygen species. Emerging studies have shown that ferroptosis plays a vital role in the progression of lung adenocarcinoma, but the effect of ferroptosis-related genes on prognosis has been poorly studied. The purpose of this study was to explore the prognostic value of ferroptosis-related genes. Methods Lung adenocarcinoma samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to establish a predictive signature for risk stratification. Kaplan–Meier (K–M) survival analysis and receiver operating characteristic (ROC) curve analysis were conducted to evaluate the signature. We further explored the potential correlation between the risk score model and tumor immune status. Results A 15-gene ferroptosis signature was constructed to classify patients into different risk groups. The overall survival (OS) of patients in the high-risk group was significantly shorter than that of patients in the low-risk group. The signature could predict OS independent of other risk factors. Single-sample gene set enrichment analysis (ssGSEA) identified the difference in immune status between the two groups. Patients in the high-risk group had stronger immune suppression, especially in the antigen presentation process. Conclusions The 15-gene ferroptosis signature identified in this study could be a potential biomarker for prognosis prediction in lung adenocarcinoma. Targeting ferroptosis might be a promising therapeutic alternative for lung adenocarcinoma.https://peerj.com/articles/11687.pdfLung adenocarcinomaFerroptosisPrognostic signatureImmune status
spellingShingle Guangxu Tu
Weilin Peng
Qidong Cai
Zhenyu Zhao
Xiong Peng
Boxue He
Pengfei Zhang
Shuai Shi
Yongguang Tao
Xiang Wang
Construction and validation of a 15-gene ferroptosis signature in lung adenocarcinoma
PeerJ
Lung adenocarcinoma
Ferroptosis
Prognostic signature
Immune status
title Construction and validation of a 15-gene ferroptosis signature in lung adenocarcinoma
title_full Construction and validation of a 15-gene ferroptosis signature in lung adenocarcinoma
title_fullStr Construction and validation of a 15-gene ferroptosis signature in lung adenocarcinoma
title_full_unstemmed Construction and validation of a 15-gene ferroptosis signature in lung adenocarcinoma
title_short Construction and validation of a 15-gene ferroptosis signature in lung adenocarcinoma
title_sort construction and validation of a 15 gene ferroptosis signature in lung adenocarcinoma
topic Lung adenocarcinoma
Ferroptosis
Prognostic signature
Immune status
url https://peerj.com/articles/11687.pdf
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