A Novel Pyroptosis-Related Gene Signature for Early-Stage Lung Squamous Cell Carcinoma
Xiaoyan Li,1,2 Jie He1,3 1Clinical Medical College of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China; 3Department of Pulmonary...
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Dove Medical Press
2021-10-01
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| Series: | International Journal of General Medicine |
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| Online Access: | https://www.dovepress.com/a-novel-pyroptosis-related-gene-signature-for-early-stage-lung-squamou-peer-reviewed-fulltext-article-IJGM |
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| author | Li X He J |
| author_facet | Li X He J |
| author_sort | Li X |
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| description | Xiaoyan Li,1,2 Jie He1,3 1Clinical Medical College of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of ChinaCorrespondence: Jie HeClinical Medical College of Chengdu Medical College, BaoGuang Street 278, Chengdu, Sichuan, 610500, People’s Republic of ChinaTel +86-28-83016637Fax +86-27-83016637Email 13540246974@163.comBackground: Diagnosis of early stage lung squamous cell carcinoma (LUSC) has improved; however, a comprehensive analysis of prognostic signatures is needed.Purpose: To identify, establish, and validate a signature model based on pyroptosis-related genes for prognostic predictions of early stage LUSC.Patients and Methods: Two independent cohorts were included. RNA-seq transcriptome data from patients with early stage LUSC were obtained from The Cancer Genome Atlas (TCGA) database. Thirty-three pyroptosis-related genes were analyzed between early stage LUSC and normal lung tissues. Cox regression analysis, random survival forest, and least absolute shrinkage and selection operator algorithms established a three-gene signature. Kaplan–Meier survival and receiver-operating characteristic curves assessed the prognostic efficacy of the model. Single-sample gene set enrichment analysis (ssGSEA) assessed the relationship between pyroptosis and immune cells. Patients with early stage LUSC from the GSE74777 dataset were used for validation. Pyroptosis-related genes were verified by RT-qPCR and Western blotting.Results: Twenty-three differentially expressed pyroptosis-related genes were identified in the LUSC and adjacent normal tissues. Three differentially expressed pyroptosis-related genes were identified as hub genes in early stage LUSC. Patients with early stage LUSC in the TCGA cohort were classified into low- and high-risk subgroups according to the risk score. Overall survival (OS) was significantly short in the high-risk subgroup versus the low-risk subgroup. A similar result was found for the GSE74777 dataset. ssGSEA of immune cells and immune-related pathways between the low- and high-risk subgroups may explain the different OS for patients with early-stage LUSC. IL-6 expression was upregulated, which was inconsistent with the bioinformatic analysis. NOD1 and CASP4 were downregulated in LUSC (all P < 0.05) versus normal lung tissues.Conclusion: Differentially expressed pyroptosis-related genes may be involved in early stage LUSC. Pyroptosis-related genes are important in tumor immunity and may be potential prognostic predictors for early stage LUSC.Keywords: early-stage lung squamous cell carcinoma, pyroptosis, prognosis, tumor microenvironment, immunotherapy |
| first_indexed | 2024-12-19T19:41:14Z |
| format | Article |
| id | doaj.art-3571bfd3b411471380c870a2a7826409 |
| institution | Directory Open Access Journal |
| issn | 1178-7074 |
| language | English |
| last_indexed | 2024-12-19T19:41:14Z |
| publishDate | 2021-10-01 |
| publisher | Dove Medical Press |
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| series | International Journal of General Medicine |
| spelling | doaj.art-3571bfd3b411471380c870a2a78264092022-12-21T20:08:14ZengDove Medical PressInternational Journal of General Medicine1178-70742021-10-01Volume 146439645369492A Novel Pyroptosis-Related Gene Signature for Early-Stage Lung Squamous Cell CarcinomaLi XHe JXiaoyan Li,1,2 Jie He1,3 1Clinical Medical College of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of ChinaCorrespondence: Jie HeClinical Medical College of Chengdu Medical College, BaoGuang Street 278, Chengdu, Sichuan, 610500, People’s Republic of ChinaTel +86-28-83016637Fax +86-27-83016637Email 13540246974@163.comBackground: Diagnosis of early stage lung squamous cell carcinoma (LUSC) has improved; however, a comprehensive analysis of prognostic signatures is needed.Purpose: To identify, establish, and validate a signature model based on pyroptosis-related genes for prognostic predictions of early stage LUSC.Patients and Methods: Two independent cohorts were included. RNA-seq transcriptome data from patients with early stage LUSC were obtained from The Cancer Genome Atlas (TCGA) database. Thirty-three pyroptosis-related genes were analyzed between early stage LUSC and normal lung tissues. Cox regression analysis, random survival forest, and least absolute shrinkage and selection operator algorithms established a three-gene signature. Kaplan–Meier survival and receiver-operating characteristic curves assessed the prognostic efficacy of the model. Single-sample gene set enrichment analysis (ssGSEA) assessed the relationship between pyroptosis and immune cells. Patients with early stage LUSC from the GSE74777 dataset were used for validation. Pyroptosis-related genes were verified by RT-qPCR and Western blotting.Results: Twenty-three differentially expressed pyroptosis-related genes were identified in the LUSC and adjacent normal tissues. Three differentially expressed pyroptosis-related genes were identified as hub genes in early stage LUSC. Patients with early stage LUSC in the TCGA cohort were classified into low- and high-risk subgroups according to the risk score. Overall survival (OS) was significantly short in the high-risk subgroup versus the low-risk subgroup. A similar result was found for the GSE74777 dataset. ssGSEA of immune cells and immune-related pathways between the low- and high-risk subgroups may explain the different OS for patients with early-stage LUSC. IL-6 expression was upregulated, which was inconsistent with the bioinformatic analysis. NOD1 and CASP4 were downregulated in LUSC (all P < 0.05) versus normal lung tissues.Conclusion: Differentially expressed pyroptosis-related genes may be involved in early stage LUSC. Pyroptosis-related genes are important in tumor immunity and may be potential prognostic predictors for early stage LUSC.Keywords: early-stage lung squamous cell carcinoma, pyroptosis, prognosis, tumor microenvironment, immunotherapyhttps://www.dovepress.com/a-novel-pyroptosis-related-gene-signature-for-early-stage-lung-squamou-peer-reviewed-fulltext-article-IJGMearly-stage lung squamous cell carcinomapyroptosisprognosistumor microenvironmentimmunotherapy. |
| spellingShingle | Li X He J A Novel Pyroptosis-Related Gene Signature for Early-Stage Lung Squamous Cell Carcinoma International Journal of General Medicine early-stage lung squamous cell carcinoma pyroptosis prognosis tumor microenvironment immunotherapy. |
| title | A Novel Pyroptosis-Related Gene Signature for Early-Stage Lung Squamous Cell Carcinoma |
| title_full | A Novel Pyroptosis-Related Gene Signature for Early-Stage Lung Squamous Cell Carcinoma |
| title_fullStr | A Novel Pyroptosis-Related Gene Signature for Early-Stage Lung Squamous Cell Carcinoma |
| title_full_unstemmed | A Novel Pyroptosis-Related Gene Signature for Early-Stage Lung Squamous Cell Carcinoma |
| title_short | A Novel Pyroptosis-Related Gene Signature for Early-Stage Lung Squamous Cell Carcinoma |
| title_sort | novel pyroptosis related gene signature for early stage lung squamous cell carcinoma |
| topic | early-stage lung squamous cell carcinoma pyroptosis prognosis tumor microenvironment immunotherapy. |
| url | https://www.dovepress.com/a-novel-pyroptosis-related-gene-signature-for-early-stage-lung-squamou-peer-reviewed-fulltext-article-IJGM |
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