Identification of key genes controlling breast cancer stem cell characteristics via stemness indices analysis
Abstract Background With the gradual unveiling of tumour heterogeneity, cancer stem cells (CSCs) are now being considered the initial component of tumour initiation. However, the mechanisms of the growth and maintenance of breast cancer (BRCA) stem cells are still unknown. Methods To explore the cru...
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doaj-29c8dd00c36f40538935a4768dd87e7b2021-02-14T12:10:28ZengBMCJournal of Translational Medicine1479-58762020-02-0118111510.1186/s12967-020-02260-9Identification of key genes controlling breast cancer stem cell characteristics via stemness indices analysisJianying Pei0Yanxia Wang1Yan Li2Gansu Provincial Maternity and Child-care HospitalGansu Provincial Maternity and Child-care HospitalGansu Province Key Laboratory of Biotherapy and Regenerative Medicine, the First Hospital of Lanzhou UniversityAbstract Background With the gradual unveiling of tumour heterogeneity, cancer stem cells (CSCs) are now being considered the initial component of tumour initiation. However, the mechanisms of the growth and maintenance of breast cancer (BRCA) stem cells are still unknown. Methods To explore the crucial genes modulating BRCA stemness characteristics, we combined the gene expression value and mRNA expression-based stemness index (mRNAsi) of samples from The Cancer Genome Atlas (TCGA), and the mRNAsi was corrected using the tumour purity (corrected mRNAsi). mRNAsi and corrected mRNAsi were analysed and showed a close relationship with BRCA clinical characteristics, including tumour depth, pathological staging and survival status. Next, weighted gene co-expression network analysis (WGCNA) was applied to distinguish crucial gene modules and key genes. A series of functional analyses and expression validation of key genes were conducted using multiple databases, including Oncomine, Gene Expression Omnibus (GEO) and Gene Expression Profiling Integrative Analysis (GEPIA). Results This study found that mRNAsi and corrected mRNAsi scores were higher in BRCA tissues than that in normal tissues, and both of them increased with tumour stage. Higher corrected mRNAsi scores showed worse overall survival outcomes. We screened 3 modules and 32 key genes, and those key genes were found to be strongly correlated with each other. Functional analysis revealed that the key genes were related to cell fate decision events such as the cell cycle, cellular senescence, chromosome segregation and mitotic nuclear division. Among 32 key genes, we identified 12 genes that strongly correlated with BRCA survival. Conclusions Thirty-two genes were found to be closely related to BRCA stem cell characteristics; among them, 12 genes showed prognosis-oriented effects in BRCA patients. The most significant signalling pathway related to stemness in BRCA was the cell cycle pathway, which may support new ideas for screening therapeutic targets to inhibit BRCA stem characteristics. These findings may highlight some therapeutic targets for inhibiting BRCA stem cells.https://doi.org/10.1186/s12967-020-02260-9Breast cancerCancer cell stemnessmRNAsiWGCNA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jianying Pei Yanxia Wang Yan Li |
spellingShingle |
Jianying Pei Yanxia Wang Yan Li Identification of key genes controlling breast cancer stem cell characteristics via stemness indices analysis Journal of Translational Medicine Breast cancer Cancer cell stemness mRNAsi WGCNA |
author_facet |
Jianying Pei Yanxia Wang Yan Li |
author_sort |
Jianying Pei |
title |
Identification of key genes controlling breast cancer stem cell characteristics via stemness indices analysis |
title_short |
Identification of key genes controlling breast cancer stem cell characteristics via stemness indices analysis |
title_full |
Identification of key genes controlling breast cancer stem cell characteristics via stemness indices analysis |
title_fullStr |
Identification of key genes controlling breast cancer stem cell characteristics via stemness indices analysis |
title_full_unstemmed |
Identification of key genes controlling breast cancer stem cell characteristics via stemness indices analysis |
title_sort |
identification of key genes controlling breast cancer stem cell characteristics via stemness indices analysis |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2020-02-01 |
description |
Abstract Background With the gradual unveiling of tumour heterogeneity, cancer stem cells (CSCs) are now being considered the initial component of tumour initiation. However, the mechanisms of the growth and maintenance of breast cancer (BRCA) stem cells are still unknown. Methods To explore the crucial genes modulating BRCA stemness characteristics, we combined the gene expression value and mRNA expression-based stemness index (mRNAsi) of samples from The Cancer Genome Atlas (TCGA), and the mRNAsi was corrected using the tumour purity (corrected mRNAsi). mRNAsi and corrected mRNAsi were analysed and showed a close relationship with BRCA clinical characteristics, including tumour depth, pathological staging and survival status. Next, weighted gene co-expression network analysis (WGCNA) was applied to distinguish crucial gene modules and key genes. A series of functional analyses and expression validation of key genes were conducted using multiple databases, including Oncomine, Gene Expression Omnibus (GEO) and Gene Expression Profiling Integrative Analysis (GEPIA). Results This study found that mRNAsi and corrected mRNAsi scores were higher in BRCA tissues than that in normal tissues, and both of them increased with tumour stage. Higher corrected mRNAsi scores showed worse overall survival outcomes. We screened 3 modules and 32 key genes, and those key genes were found to be strongly correlated with each other. Functional analysis revealed that the key genes were related to cell fate decision events such as the cell cycle, cellular senescence, chromosome segregation and mitotic nuclear division. Among 32 key genes, we identified 12 genes that strongly correlated with BRCA survival. Conclusions Thirty-two genes were found to be closely related to BRCA stem cell characteristics; among them, 12 genes showed prognosis-oriented effects in BRCA patients. The most significant signalling pathway related to stemness in BRCA was the cell cycle pathway, which may support new ideas for screening therapeutic targets to inhibit BRCA stem characteristics. These findings may highlight some therapeutic targets for inhibiting BRCA stem cells. |
topic |
Breast cancer Cancer cell stemness mRNAsi WGCNA |
url |
https://doi.org/10.1186/s12967-020-02260-9 |
work_keys_str_mv |
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