A disulfidptosis-related lncRNA prognostic model to predict survival and response to immunotherapy in lung adenocarcinoma

Frontiers in Pharmacology

Pharmacology

Jian-Yan Pan¹  Hai-Bo Zhang²  Tao Zhu³ 

[1] Department of Birth Health and Genetics, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning, China;Department of Pharmacy, Hangzhou Women’s Hospital, Hangzhou Maternity and Child Health Care Hospital, Hangzhou, China;Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;Key Laboratory of Intelligent Pharmacy and Individualized Therapy of Huzhou, Department of Pharmacy, Changxing People’s Hospital, Hangzhou, China;

关键词: lung adenocarcinoma;    disulfidptosis;    lncRNA;    prognosis;    immunotherapy;   

DOI  :  10.3389/fphar.2023.1254119

 received in 2023-07-06, accepted in 2023-09-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Lung adenocarcinoma (LUAD) is the major subtype of lung cancer and has a poor prognosis. Disulfidptosis is a novel regulated cell death form characterized by aberrant disulfide stress and actin network collapse. This study aimed to identify disulfidptosis-related lncRNAs, and predict LUAD patients’ prognosis and response to antitumor therapies by establishing a disulfidptosis-related lncRNA model.Methods: Transcriptome and clinical data of LUAD patients were obtained from the TCGA database. Pearson correlation and Cox regression analysis was used to identify disulfidptosis-related lncRNAs associated with overall survival. LASSO regression analysis was adopted to construct the prognostic model. GO, KEGG and GSEA analysis was used to identify cellular pathways related to this model. Immune cell infiltration was investigated by ESTIMATE and CIBERSORT algorithms. Tumor mutational burden (TMB) and its association with model-derived risk score were analyzed using simple nucleotide variation data. Patients’ response to immunotherapy and other antineoplastic drugs was predicted by the TIDE algorithm and GDSC tool, respectively.Results: We identified 127 disulfidptosis-related lncRNAs, and a prognostic model that consists eight of them (KTN1-AS1, AL365181.3, MANCR, LINC01352, AC090559.1, AC093673.1, AP001094.3, and MHENCR) was established and verified. The prognostic model could stratify LUAD patients into two distinct risk-score groups. A high risk score was an independent prognosis factor indicating poor overall survival, and correlated with reduced immune cell infiltration, high TMB, and lower activity of tumor immune response. Immune checkpoint blockade might bring more survival benefits to the high-risk LUAD patients, whereas low-risk patients might be more responsive to targeted therapy and diverse kinase inhibitors.Conclusion: We established a disulfidptosis-related lncRNA model that can be exploited to predict the prognosis, tumor mutational burden, immune cell infiltration landscape, and response to immunotherapy and targeted therapy in LUAD patients.

【 授权许可】

Unknown   
Copyright © 2023 Zhang, Pan and Zhu.