A ferroptosis-related gene signature for overall survival prediction and immune infiltration in lung squamous cell carcinoma

Background: Ferroptosis is associated with cancer initiation and progression. However, the molecular mechanism and prognostic value of ferroptosis-related genes in lung squamous cell carcinoma (LUSC) are poorly understood. Methods: The mRNA expression profiles, methylation data, and clinical informa...

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Autores principales: Miao, Ti-wei, Yang, De-qing, Chen, Fang-ying, Zhu, Qi, Chen, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434561/
https://www.ncbi.nlm.nih.gov/pubmed/35866375
http://dx.doi.org/10.1042/BSR20212835
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author Miao, Ti-wei
Yang, De-qing
Chen, Fang-ying
Zhu, Qi
Chen, Xin
author_facet Miao, Ti-wei
Yang, De-qing
Chen, Fang-ying
Zhu, Qi
Chen, Xin
author_sort Miao, Ti-wei
collection PubMed
description Background: Ferroptosis is associated with cancer initiation and progression. However, the molecular mechanism and prognostic value of ferroptosis-related genes in lung squamous cell carcinoma (LUSC) are poorly understood. Methods: The mRNA expression profiles, methylation data, and clinical information of patients with LUSC were downloaded from TCGA and GEO database. Ferroptosis-related differentially expressed genes (DEGs) were identified between cancerous and non-cancerous tissues, and their prognostic value was systemically investigated by bioinformatic analyses. Results: A ferroptosis-related gene signature (ALOX5, TFRC, PHKG2, FADS2, NOX1) was constructed using multivariate Cox regression analysis and represented as a risk score. Overall survival (OS) probability was significantly lower in the high-risk group than in the low-risk group (P<0.001), and receiver operating characteristic curve showed a good predictive capacity (AUC = 0.739). The risk score was an independent prognostic factor for LUSC. A nomogram was constructed to predict the OS probabilities at 1, 3, and 5 years. High-risk score was associated with increased immune infiltration, lower methylation levels, higher immune checkpoint genes expression levels, and better chemotherapy response. Cell adhesion molecules, focal adhesion, and extracellular matrix receptor interaction were the main pathways in the high-risk group. The signature was validated using the TCGA test cohort, entire TCGA cohort, GSE30219, GSE157010, GSE73403, and GSE4573 datasets. The gene disorders in patients with LUSC were validated using real-time PCR and single-cell RNA sequencing analysis. Conclusions: A ferroptosis-related gene signature was constructed to predict OS probability in LUSC. This could facilitate novel therapeutic methods and guide individualized therapy.
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spelling pubmed-94345612022-09-07 A ferroptosis-related gene signature for overall survival prediction and immune infiltration in lung squamous cell carcinoma Miao, Ti-wei Yang, De-qing Chen, Fang-ying Zhu, Qi Chen, Xin Biosci Rep Bioinformatics Background: Ferroptosis is associated with cancer initiation and progression. However, the molecular mechanism and prognostic value of ferroptosis-related genes in lung squamous cell carcinoma (LUSC) are poorly understood. Methods: The mRNA expression profiles, methylation data, and clinical information of patients with LUSC were downloaded from TCGA and GEO database. Ferroptosis-related differentially expressed genes (DEGs) were identified between cancerous and non-cancerous tissues, and their prognostic value was systemically investigated by bioinformatic analyses. Results: A ferroptosis-related gene signature (ALOX5, TFRC, PHKG2, FADS2, NOX1) was constructed using multivariate Cox regression analysis and represented as a risk score. Overall survival (OS) probability was significantly lower in the high-risk group than in the low-risk group (P<0.001), and receiver operating characteristic curve showed a good predictive capacity (AUC = 0.739). The risk score was an independent prognostic factor for LUSC. A nomogram was constructed to predict the OS probabilities at 1, 3, and 5 years. High-risk score was associated with increased immune infiltration, lower methylation levels, higher immune checkpoint genes expression levels, and better chemotherapy response. Cell adhesion molecules, focal adhesion, and extracellular matrix receptor interaction were the main pathways in the high-risk group. The signature was validated using the TCGA test cohort, entire TCGA cohort, GSE30219, GSE157010, GSE73403, and GSE4573 datasets. The gene disorders in patients with LUSC were validated using real-time PCR and single-cell RNA sequencing analysis. Conclusions: A ferroptosis-related gene signature was constructed to predict OS probability in LUSC. This could facilitate novel therapeutic methods and guide individualized therapy. Portland Press Ltd. 2022-08-31 /pmc/articles/PMC9434561/ /pubmed/35866375 http://dx.doi.org/10.1042/BSR20212835 Text en © 2022 The Author(s). https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Bioinformatics
Miao, Ti-wei
Yang, De-qing
Chen, Fang-ying
Zhu, Qi
Chen, Xin
A ferroptosis-related gene signature for overall survival prediction and immune infiltration in lung squamous cell carcinoma
title A ferroptosis-related gene signature for overall survival prediction and immune infiltration in lung squamous cell carcinoma
title_full A ferroptosis-related gene signature for overall survival prediction and immune infiltration in lung squamous cell carcinoma
title_fullStr A ferroptosis-related gene signature for overall survival prediction and immune infiltration in lung squamous cell carcinoma
title_full_unstemmed A ferroptosis-related gene signature for overall survival prediction and immune infiltration in lung squamous cell carcinoma
title_short A ferroptosis-related gene signature for overall survival prediction and immune infiltration in lung squamous cell carcinoma
title_sort ferroptosis-related gene signature for overall survival prediction and immune infiltration in lung squamous cell carcinoma
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434561/
https://www.ncbi.nlm.nih.gov/pubmed/35866375
http://dx.doi.org/10.1042/BSR20212835
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