A disulfidptosis-related lncRNA signature for predicting prognosis and evaluating the tumor immune microenvironment of lung adenocarcinoma

Abstract As a novel form of regulated cell death (RCD), disulfidptosis offering a significant opportunity in better understanding of tumor pathogenesis and therapeutic strategies. Long non-coding RNAs (lncRNAs) regulate the biology functions of tumor cells by engaging with a range of targets. Howeve...

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Main Authors: Zipei Song, Xincen Cao, Xiaokun Wang, Yuting Li, Weiran Zhang, Yuheng Wang, Liang Chen
Format: Article
Language:English
Published: Nature Portfolio 2024-02-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-024-55201-7
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author Zipei Song
Xincen Cao
Xiaokun Wang
Yuting Li
Weiran Zhang
Yuheng Wang
Liang Chen
author_facet Zipei Song
Xincen Cao
Xiaokun Wang
Yuting Li
Weiran Zhang
Yuheng Wang
Liang Chen
author_sort Zipei Song
collection DOAJ
description Abstract As a novel form of regulated cell death (RCD), disulfidptosis offering a significant opportunity in better understanding of tumor pathogenesis and therapeutic strategies. Long non-coding RNAs (lncRNAs) regulate the biology functions of tumor cells by engaging with a range of targets. However, the prognostic value of disulfidptosis-related lncRNAs (DRlncRNAs) in lung adenocarcinoma (LUAD) remains unclear. Therefore, our study aimed at establishing a prognostic model for LUAD patients based on DRlncRNAs. RNA-seq data and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Subsequently, a prognostic model based on DRlncRNAs was constructed using LASSO and COX regression analysis. Patients were stratified into high- and low-risk groups based on their risk scores. Differences between the high-risk and low-risk groups were investigated in terms of overall survival (OS), functional enrichment, tumor immune microenvironment (TIME), somatic mutations, and drug sensitivity. Finally, the role of lncRNA GSEC in LUAD was validated through in vitro experiments. Using the prognostic model consists of 5 DRlncRNAs (AL365181.2, GSEC, AC093673.1, AC012615.1, AL606834.1), the low-risk group exhibited a markedly superior survival in comparison to the high-risk group. The significant differences were observed among patients from different risk groups in OS, immune cell infiltration, immune checkpoint expression, immunotherapy response, and mutation landscape. Experimental results from cellular studies demonstrate the knockdown of lncRNA GSEC leading to a significant reduction in the proliferation and migration abilities of LUAD cells. Our prognostic model, constructed using 5 DRlncRNAs, exhibited the capacity to independently predict the survival of LUAD patients, providing the potentially significant assistance in prognosis prediction, and treatment effects optimization. Moreover, our study established a foundation for further research on disulfidptosis in LUAD and proposed new perspectives for the treatment of LUAD.
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spelling doaj.art-821aa173b6de40fcb37116db181b8ddd2024-03-05T18:44:43ZengNature PortfolioScientific Reports2045-23222024-02-0114111910.1038/s41598-024-55201-7A disulfidptosis-related lncRNA signature for predicting prognosis and evaluating the tumor immune microenvironment of lung adenocarcinomaZipei Song0Xincen Cao1Xiaokun Wang2Yuting Li3Weiran Zhang4Yuheng Wang5Liang Chen6Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical UniversityThe First Affiliated Hospital of Nanjing Medical UniversityDepartment of Graduate Administration, Chinese PLA General HospitalDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical UniversityAbstract As a novel form of regulated cell death (RCD), disulfidptosis offering a significant opportunity in better understanding of tumor pathogenesis and therapeutic strategies. Long non-coding RNAs (lncRNAs) regulate the biology functions of tumor cells by engaging with a range of targets. However, the prognostic value of disulfidptosis-related lncRNAs (DRlncRNAs) in lung adenocarcinoma (LUAD) remains unclear. Therefore, our study aimed at establishing a prognostic model for LUAD patients based on DRlncRNAs. RNA-seq data and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Subsequently, a prognostic model based on DRlncRNAs was constructed using LASSO and COX regression analysis. Patients were stratified into high- and low-risk groups based on their risk scores. Differences between the high-risk and low-risk groups were investigated in terms of overall survival (OS), functional enrichment, tumor immune microenvironment (TIME), somatic mutations, and drug sensitivity. Finally, the role of lncRNA GSEC in LUAD was validated through in vitro experiments. Using the prognostic model consists of 5 DRlncRNAs (AL365181.2, GSEC, AC093673.1, AC012615.1, AL606834.1), the low-risk group exhibited a markedly superior survival in comparison to the high-risk group. The significant differences were observed among patients from different risk groups in OS, immune cell infiltration, immune checkpoint expression, immunotherapy response, and mutation landscape. Experimental results from cellular studies demonstrate the knockdown of lncRNA GSEC leading to a significant reduction in the proliferation and migration abilities of LUAD cells. Our prognostic model, constructed using 5 DRlncRNAs, exhibited the capacity to independently predict the survival of LUAD patients, providing the potentially significant assistance in prognosis prediction, and treatment effects optimization. Moreover, our study established a foundation for further research on disulfidptosis in LUAD and proposed new perspectives for the treatment of LUAD.https://doi.org/10.1038/s41598-024-55201-7Lung adenocarcinomaDisulfidptosisLncRNAPrognosisTumor immune microenvironment
spellingShingle Zipei Song
Xincen Cao
Xiaokun Wang
Yuting Li
Weiran Zhang
Yuheng Wang
Liang Chen
A disulfidptosis-related lncRNA signature for predicting prognosis and evaluating the tumor immune microenvironment of lung adenocarcinoma
Scientific Reports
Lung adenocarcinoma
Disulfidptosis
LncRNA
Prognosis
Tumor immune microenvironment
title A disulfidptosis-related lncRNA signature for predicting prognosis and evaluating the tumor immune microenvironment of lung adenocarcinoma
title_full A disulfidptosis-related lncRNA signature for predicting prognosis and evaluating the tumor immune microenvironment of lung adenocarcinoma
title_fullStr A disulfidptosis-related lncRNA signature for predicting prognosis and evaluating the tumor immune microenvironment of lung adenocarcinoma
title_full_unstemmed A disulfidptosis-related lncRNA signature for predicting prognosis and evaluating the tumor immune microenvironment of lung adenocarcinoma
title_short A disulfidptosis-related lncRNA signature for predicting prognosis and evaluating the tumor immune microenvironment of lung adenocarcinoma
title_sort disulfidptosis related lncrna signature for predicting prognosis and evaluating the tumor immune microenvironment of lung adenocarcinoma
topic Lung adenocarcinoma
Disulfidptosis
LncRNA
Prognosis
Tumor immune microenvironment
url https://doi.org/10.1038/s41598-024-55201-7
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