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Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

BACKGROUND: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be...

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Autores principales: Peng, Wei, Li, Jian-Di, Zeng, Jing-Jing, Zou, Xiao-Ping, Tang, Deng, Tang, Wei, Rong, Min-Hua, Li, Ying, Dai, Wen-Bin, Tang, Zhong-Qing, Feng, Zhen-Bo, Chen, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427770/
https://www.ncbi.nlm.nih.gov/pubmed/32818022
http://dx.doi.org/10.1186/s12935-020-01465-8
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author Peng, Wei
Li, Jian-Di
Zeng, Jing-Jing
Zou, Xiao-Ping
Tang, Deng
Tang, Wei
Rong, Min-Hua
Li, Ying
Dai, Wen-Bin
Tang, Zhong-Qing
Feng, Zhen-Bo
Chen, Gang
author_facet Peng, Wei
Li, Jian-Di
Zeng, Jing-Jing
Zou, Xiao-Ping
Tang, Deng
Tang, Wei
Rong, Min-Hua
Li, Ying
Dai, Wen-Bin
Tang, Zhong-Qing
Feng, Zhen-Bo
Chen, Gang
author_sort Peng, Wei
collection PubMed
description BACKGROUND: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. METHODS: Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. RESULTS: COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55–1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76–0.83) with sensitivity of 0.77 (95% CI 0.69–0.83) and specificity of 0.70 (95% CI 0.61–0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. CONCLUSIONS: Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.
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spelling pubmed-74277702020-08-17 Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis Peng, Wei Li, Jian-Di Zeng, Jing-Jing Zou, Xiao-Ping Tang, Deng Tang, Wei Rong, Min-Hua Li, Ying Dai, Wen-Bin Tang, Zhong-Qing Feng, Zhen-Bo Chen, Gang Cancer Cell Int Primary Research BACKGROUND: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. METHODS: Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. RESULTS: COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55–1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76–0.83) with sensitivity of 0.77 (95% CI 0.69–0.83) and specificity of 0.70 (95% CI 0.61–0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. CONCLUSIONS: Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer. BioMed Central 2020-08-14 /pmc/articles/PMC7427770/ /pubmed/32818022 http://dx.doi.org/10.1186/s12935-020-01465-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Peng, Wei
Li, Jian-Di
Zeng, Jing-Jing
Zou, Xiao-Ping
Tang, Deng
Tang, Wei
Rong, Min-Hua
Li, Ying
Dai, Wen-Bin
Tang, Zhong-Qing
Feng, Zhen-Bo
Chen, Gang
Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis
title Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis
title_full Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis
title_fullStr Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis
title_full_unstemmed Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis
title_short Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis
title_sort clinical value and potential mechanisms of col8a1 upregulation in breast cancer: a comprehensive analysis
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427770/
https://www.ncbi.nlm.nih.gov/pubmed/32818022
http://dx.doi.org/10.1186/s12935-020-01465-8
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