Identification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis‐related genes

Abstract Background Lung squamous cell carcinoma (LUSC), one of the main pathological types of lung cancer, has led to consequential socioeconomic burden. Ferroptosis is an iron‐dependent form of cell death process with potentials for therapeutic target in various kinds of tumors. However, whether f...

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Autores principales: Xiayao Diao, Chao Guo, Lei Liu, Guige Wang, Shanqing Li
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Publicado: Wiley 2021
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spelling oai:doaj.org-article:54bd4be3f71149b788d9fd9a9fdd354b2021-12-02T02:34:55ZIdentification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis‐related genes1759-77141759-770610.1111/1759-7714.14195https://doaj.org/article/54bd4be3f71149b788d9fd9a9fdd354b2021-12-01T00:00:00Zhttps://doi.org/10.1111/1759-7714.14195https://doaj.org/toc/1759-7706https://doaj.org/toc/1759-7714Abstract Background Lung squamous cell carcinoma (LUSC), one of the main pathological types of lung cancer, has led to consequential socioeconomic burden. Ferroptosis is an iron‐dependent form of cell death process with potentials for therapeutic target in various kinds of tumors. However, whether ferroptosis‐related genes (FRGs) are associated with the prognosis of LUSC patients is still unclear. The aim of this study was to establish a FRGs‐based signature which could stratify patients with LUSC. Methods The RNA sequencing profiles and corresponding clinical data of LUSC patients were retrieved from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) dataset. A FRG‐based signature was developed using the TCGA‐LUSC cohort and validated in the GEO cohort. Gene set enrichment analysis (GSEA) and analysis of immune cell characteristics were conducted to assess the relationship between FRGs and biological function or immune status. A nomogram based on selected clinical factors and the risk scores which were generated from the FRG‐based signature was developed using the TCGA cohort and validated in the GEO cohort. Results A set of 16 FRGs, significantly associated with overall survival (OS) in the TCGA cohort, was identified and could classify LUSC patients into two risk groups. Kaplan–Meier analysis illustrated that the survival rate of the high‐risk group was significantly lower than the low‐risk group. Assessment and external validation of the signature showed that the survival predictive performance of this signature was adequate. Additionally, multiple pathways and functions were enriched through GSEA and the analysis of immune cell characteristics showed significantly different abundances of immune cells among the two risk groups. Finally, a nomogram integrating the FRG‐based signature and selected clinical factors was also developed and assessed in both the TCGA and GEO cohort. Conclusion This study indicated the association between the FRGs and prognosis of patients with LUSC. Targeting ferroptosis may serve as a novel potential therapeutic alternative for LUSC.Xiayao DiaoChao GuoLei LiuGuige WangShanqing LiWileyarticleferroptosislung squamous cell carcinomaoverall survivalprognostic signatureNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENThoracic Cancer, Vol 12, Iss 23, Pp 3236-3247 (2021)
institution DOAJ
collection DOAJ
language EN
topic ferroptosis
lung squamous cell carcinoma
overall survival
prognostic signature
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle ferroptosis
lung squamous cell carcinoma
overall survival
prognostic signature
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Xiayao Diao
Chao Guo
Lei Liu
Guige Wang
Shanqing Li
Identification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis‐related genes
description Abstract Background Lung squamous cell carcinoma (LUSC), one of the main pathological types of lung cancer, has led to consequential socioeconomic burden. Ferroptosis is an iron‐dependent form of cell death process with potentials for therapeutic target in various kinds of tumors. However, whether ferroptosis‐related genes (FRGs) are associated with the prognosis of LUSC patients is still unclear. The aim of this study was to establish a FRGs‐based signature which could stratify patients with LUSC. Methods The RNA sequencing profiles and corresponding clinical data of LUSC patients were retrieved from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) dataset. A FRG‐based signature was developed using the TCGA‐LUSC cohort and validated in the GEO cohort. Gene set enrichment analysis (GSEA) and analysis of immune cell characteristics were conducted to assess the relationship between FRGs and biological function or immune status. A nomogram based on selected clinical factors and the risk scores which were generated from the FRG‐based signature was developed using the TCGA cohort and validated in the GEO cohort. Results A set of 16 FRGs, significantly associated with overall survival (OS) in the TCGA cohort, was identified and could classify LUSC patients into two risk groups. Kaplan–Meier analysis illustrated that the survival rate of the high‐risk group was significantly lower than the low‐risk group. Assessment and external validation of the signature showed that the survival predictive performance of this signature was adequate. Additionally, multiple pathways and functions were enriched through GSEA and the analysis of immune cell characteristics showed significantly different abundances of immune cells among the two risk groups. Finally, a nomogram integrating the FRG‐based signature and selected clinical factors was also developed and assessed in both the TCGA and GEO cohort. Conclusion This study indicated the association between the FRGs and prognosis of patients with LUSC. Targeting ferroptosis may serve as a novel potential therapeutic alternative for LUSC.
format article
author Xiayao Diao
Chao Guo
Lei Liu
Guige Wang
Shanqing Li
author_facet Xiayao Diao
Chao Guo
Lei Liu
Guige Wang
Shanqing Li
author_sort Xiayao Diao
title Identification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis‐related genes
title_short Identification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis‐related genes
title_full Identification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis‐related genes
title_fullStr Identification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis‐related genes
title_full_unstemmed Identification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis‐related genes
title_sort identification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis‐related genes
publisher Wiley
publishDate 2021
url https://doaj.org/article/54bd4be3f71149b788d9fd9a9fdd354b
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AT leiliu identificationandvalidationofanindividualizedprognosticsignatureoflungsquamouscellcarcinomabasedonferroptosisrelatedgenes
AT guigewang identificationandvalidationofanindividualizedprognosticsignatureoflungsquamouscellcarcinomabasedonferroptosisrelatedgenes
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