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A Prognostic Signature Consisting of Pyroptosis-Related Genes and SCAF11 for Predicting Immune Response in Breast Cancer

Pyroptosis, characterized as an inflammasome-mediated cell death pathway, may be participated in tumorigenesis and progression. However, the underlying molecular function and mechanism of pyroptosis in BRCA remain unclear. In our study, we aimed to develop a prognostic signature in BRCA based on pyr...

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Autores principales: Chu, Ling, Yi, Qiaoli, Yan, Yuanliang, Peng, Jinwu, Li, Zhilan, Jiang, Feng, He, Qingchun, Ouyang, Lingzi, Wu, Shangjun, Fu, Chencheng, Liu, Ying, Xu, Zhijie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133489/
https://www.ncbi.nlm.nih.gov/pubmed/35646948
http://dx.doi.org/10.3389/fmed.2022.882763
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author Chu, Ling
Yi, Qiaoli
Yan, Yuanliang
Peng, Jinwu
Li, Zhilan
Jiang, Feng
He, Qingchun
Ouyang, Lingzi
Wu, Shangjun
Fu, Chencheng
Liu, Ying
Xu, Zhijie
author_facet Chu, Ling
Yi, Qiaoli
Yan, Yuanliang
Peng, Jinwu
Li, Zhilan
Jiang, Feng
He, Qingchun
Ouyang, Lingzi
Wu, Shangjun
Fu, Chencheng
Liu, Ying
Xu, Zhijie
author_sort Chu, Ling
collection PubMed
description Pyroptosis, characterized as an inflammasome-mediated cell death pathway, may be participated in tumorigenesis and progression. However, the underlying molecular function and mechanism of pyroptosis in BRCA remain unclear. In our study, we aimed to develop a prognostic signature in BRCA based on pyroptosis-associated genes. Data was downloaded from TCGA database, and then we screened 760 female BRCA samples and 104 normal breast tissues as the training set. Seven pyroptosis-related genes (CASP9, GPX4, IL18, NLRC4, SCAF11, TIRAP, and TNF) were identified as the pyroptosis-related prognostic model for BRCA using LASSO Cox regression. We subsequently tested the prognostic value of pyroptosis-associated gene signature in a validation set, GSE 20685. Time-dependent receiver operating characteristic analysis demonstrated the credible predictive capacity of this pyroptosis-associated gene signature. The area under the curves were 0.806 at 3 years, 0.787 at 5 years, 0.775 at 8 years, and 0.793 at 10 years in the training set, and 0.824 at 5 years, 0.808 at 8 years, and 0.790 at 10 years in the validation set. Furthermore, there are currently few data on SCAF11 regulating pyroptosis. To clarify this issue, we performed integrative bioinformatics and experimental analysis. Knocking down SCAF11 possessed an anti-cancer effect in terms of inhibiting cell viability and suppressing colony-formation in in-vitro functional assays. Meanwhile, the biological functions of SCAF11 in BRCA were further validated with several algorithms, such as Xiantao tool, LinkedOmics, GEPIA2, and TISIDB. These findings indicated that the expression of SCAF11 was significantly correlated with diverse tumor-infiltrating lymphocytes (TILs), including T central memory cell (Tcm), and type 2 T helper cell (Th2), etc. Functional enrichment analysis suggested that co-expression genes of SCAF11 primarily participated in inflammation and immune-related signaling pathways, such as oxidative phosphorylation, antimicrobial humoral response, and immunoglobulin complex. Moreover, SCAF11 expression was positively correlated with several immune checkpoints, including PD-L1, B7H3, and PDCD1LG2. Taken together, this study uncovered that pyroptosis-associated gene signature might be applied as an effective independent predictor in patients with BRCA. The pyroptosis-related gene SCAF11 might play potential roles in the regulation of immune microenvironment in BRCA.
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spelling pubmed-91334892022-05-27 A Prognostic Signature Consisting of Pyroptosis-Related Genes and SCAF11 for Predicting Immune Response in Breast Cancer Chu, Ling Yi, Qiaoli Yan, Yuanliang Peng, Jinwu Li, Zhilan Jiang, Feng He, Qingchun Ouyang, Lingzi Wu, Shangjun Fu, Chencheng Liu, Ying Xu, Zhijie Front Med (Lausanne) Medicine Pyroptosis, characterized as an inflammasome-mediated cell death pathway, may be participated in tumorigenesis and progression. However, the underlying molecular function and mechanism of pyroptosis in BRCA remain unclear. In our study, we aimed to develop a prognostic signature in BRCA based on pyroptosis-associated genes. Data was downloaded from TCGA database, and then we screened 760 female BRCA samples and 104 normal breast tissues as the training set. Seven pyroptosis-related genes (CASP9, GPX4, IL18, NLRC4, SCAF11, TIRAP, and TNF) were identified as the pyroptosis-related prognostic model for BRCA using LASSO Cox regression. We subsequently tested the prognostic value of pyroptosis-associated gene signature in a validation set, GSE 20685. Time-dependent receiver operating characteristic analysis demonstrated the credible predictive capacity of this pyroptosis-associated gene signature. The area under the curves were 0.806 at 3 years, 0.787 at 5 years, 0.775 at 8 years, and 0.793 at 10 years in the training set, and 0.824 at 5 years, 0.808 at 8 years, and 0.790 at 10 years in the validation set. Furthermore, there are currently few data on SCAF11 regulating pyroptosis. To clarify this issue, we performed integrative bioinformatics and experimental analysis. Knocking down SCAF11 possessed an anti-cancer effect in terms of inhibiting cell viability and suppressing colony-formation in in-vitro functional assays. Meanwhile, the biological functions of SCAF11 in BRCA were further validated with several algorithms, such as Xiantao tool, LinkedOmics, GEPIA2, and TISIDB. These findings indicated that the expression of SCAF11 was significantly correlated with diverse tumor-infiltrating lymphocytes (TILs), including T central memory cell (Tcm), and type 2 T helper cell (Th2), etc. Functional enrichment analysis suggested that co-expression genes of SCAF11 primarily participated in inflammation and immune-related signaling pathways, such as oxidative phosphorylation, antimicrobial humoral response, and immunoglobulin complex. Moreover, SCAF11 expression was positively correlated with several immune checkpoints, including PD-L1, B7H3, and PDCD1LG2. Taken together, this study uncovered that pyroptosis-associated gene signature might be applied as an effective independent predictor in patients with BRCA. The pyroptosis-related gene SCAF11 might play potential roles in the regulation of immune microenvironment in BRCA. Frontiers Media S.A. 2022-05-12 /pmc/articles/PMC9133489/ /pubmed/35646948 http://dx.doi.org/10.3389/fmed.2022.882763 Text en Copyright © 2022 Chu, Yi, Yan, Peng, Li, Jiang, He, Ouyang, Wu, Fu, Liu and Xu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Chu, Ling
Yi, Qiaoli
Yan, Yuanliang
Peng, Jinwu
Li, Zhilan
Jiang, Feng
He, Qingchun
Ouyang, Lingzi
Wu, Shangjun
Fu, Chencheng
Liu, Ying
Xu, Zhijie
A Prognostic Signature Consisting of Pyroptosis-Related Genes and SCAF11 for Predicting Immune Response in Breast Cancer
title A Prognostic Signature Consisting of Pyroptosis-Related Genes and SCAF11 for Predicting Immune Response in Breast Cancer
title_full A Prognostic Signature Consisting of Pyroptosis-Related Genes and SCAF11 for Predicting Immune Response in Breast Cancer
title_fullStr A Prognostic Signature Consisting of Pyroptosis-Related Genes and SCAF11 for Predicting Immune Response in Breast Cancer
title_full_unstemmed A Prognostic Signature Consisting of Pyroptosis-Related Genes and SCAF11 for Predicting Immune Response in Breast Cancer
title_short A Prognostic Signature Consisting of Pyroptosis-Related Genes and SCAF11 for Predicting Immune Response in Breast Cancer
title_sort prognostic signature consisting of pyroptosis-related genes and scaf11 for predicting immune response in breast cancer
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133489/
https://www.ncbi.nlm.nih.gov/pubmed/35646948
http://dx.doi.org/10.3389/fmed.2022.882763
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