The initial expression alterations occurring to transcription factors during the formation of breast cancer: Evidence from bioinformatics
Abstract Background Breast cancer (BC) is the leading malignancy among women worldwide. Aim This work aimed to present a comprehensively bioinformatic analysis of gene expression profiles and to identify the hub genes during BC tumorigenesis, providing potential biomarkers and targets for the diagno...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-03-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.4545 |
| _version_ | 1818492595990429696 |
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| author | Xingxing Dong Yalong Yang Gaoran Xu Zelin Tian Qian Yang Yan Gong Gaosong Wu |
| author_facet | Xingxing Dong Yalong Yang Gaoran Xu Zelin Tian Qian Yang Yan Gong Gaosong Wu |
| author_sort | Xingxing Dong |
| collection | DOAJ |
| description | Abstract Background Breast cancer (BC) is the leading malignancy among women worldwide. Aim This work aimed to present a comprehensively bioinformatic analysis of gene expression profiles and to identify the hub genes during BC tumorigenesis, providing potential biomarkers and targets for the diagnosis and therapy of BC. Materials & Methods In this study, multiple public databases, bioinformatics approaches, and online analytical tools were employed and the real‐time reverse transcription polymerase chain reaction was implemented. Results First, we identified 10, 107, and 3869 differentially expressed genes (DEGs) from three gene expression datasets (GSE9574, GSE15852, and GSE42568, covering normal, para‐cancerous, and BC samples, respectively), and investigated different biological functions and pathways involved. Then, we screened out 8, 16, and 29 module genes from these DEGs, respectively. Next, 10 candidate genes were determined through expression and survival analyses. We noted that seven candidate genes JUN, FOS, FOSB, EGR1, ZFP36, CFD, and PPARG were downregulated in BC compared to normal tissues and lower expressed in aggressive types of BC (basal, HER2+, and luminal B), TP53 mutation group, younger patients, higher stage BC, and lymph node metastasis BC, while CD27, PSMB9, and SELL were upregulated. The present study discovered that the expression levels of these candidate genes were correlated with the infiltration of immune cells (CD8+ T cell, macrophage, natural killer [NK] cell, and cancer‐associated fibroblast) in BC, as well as biomarkers of immune cells and immune checkpoints. We also revealed that promoter methylation, amplification, and deep deletion might contribute to the abnormal expressions of candidate genes. Moreover, we illustrated downstream‐targeted genes of JUN, FOS, FOSB, EGR1, and ZFP36 and demonstrated that these targeted genes were involved in “positive regulation of cell death”, “pathways in cancer”, “PI3K‐Akt signaling pathway”, and so on. Discussion & Conclusion We presented differential gene expression profiles among normal, para‐cancerous, and BC tissues and further identified candidate genes that might contribute to tumorigenesis and progression of BC, as potential diagnostic and prognostic targets for BC patients. |
| first_indexed | 2024-12-10T17:45:13Z |
| format | Article |
| id | doaj.art-fa74a4f72bc14b87b184a454488914d0 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-10T17:45:13Z |
| publishDate | 2022-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-fa74a4f72bc14b87b184a454488914d02022-12-22T01:39:16ZengWileyCancer Medicine2045-76342022-03-011151371139510.1002/cam4.4545The initial expression alterations occurring to transcription factors during the formation of breast cancer: Evidence from bioinformaticsXingxing Dong0Yalong Yang1Gaoran Xu2Zelin Tian3Qian Yang4Yan Gong5Gaosong Wu6Department of Thyroid and Breast Surgery Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Thyroid and Breast Surgery Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Thyroid and Breast Surgery Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Thyroid and Breast Surgery Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Thyroid and Breast Surgery Zhongnan Hospital of Wuhan University Wuhan ChinaTumor Precision Diagnosis and Treatment Technology and Translational Medicine Hubei Engineering Research Center Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Thyroid and Breast Surgery Zhongnan Hospital of Wuhan University Wuhan ChinaAbstract Background Breast cancer (BC) is the leading malignancy among women worldwide. Aim This work aimed to present a comprehensively bioinformatic analysis of gene expression profiles and to identify the hub genes during BC tumorigenesis, providing potential biomarkers and targets for the diagnosis and therapy of BC. Materials & Methods In this study, multiple public databases, bioinformatics approaches, and online analytical tools were employed and the real‐time reverse transcription polymerase chain reaction was implemented. Results First, we identified 10, 107, and 3869 differentially expressed genes (DEGs) from three gene expression datasets (GSE9574, GSE15852, and GSE42568, covering normal, para‐cancerous, and BC samples, respectively), and investigated different biological functions and pathways involved. Then, we screened out 8, 16, and 29 module genes from these DEGs, respectively. Next, 10 candidate genes were determined through expression and survival analyses. We noted that seven candidate genes JUN, FOS, FOSB, EGR1, ZFP36, CFD, and PPARG were downregulated in BC compared to normal tissues and lower expressed in aggressive types of BC (basal, HER2+, and luminal B), TP53 mutation group, younger patients, higher stage BC, and lymph node metastasis BC, while CD27, PSMB9, and SELL were upregulated. The present study discovered that the expression levels of these candidate genes were correlated with the infiltration of immune cells (CD8+ T cell, macrophage, natural killer [NK] cell, and cancer‐associated fibroblast) in BC, as well as biomarkers of immune cells and immune checkpoints. We also revealed that promoter methylation, amplification, and deep deletion might contribute to the abnormal expressions of candidate genes. Moreover, we illustrated downstream‐targeted genes of JUN, FOS, FOSB, EGR1, and ZFP36 and demonstrated that these targeted genes were involved in “positive regulation of cell death”, “pathways in cancer”, “PI3K‐Akt signaling pathway”, and so on. Discussion & Conclusion We presented differential gene expression profiles among normal, para‐cancerous, and BC tissues and further identified candidate genes that might contribute to tumorigenesis and progression of BC, as potential diagnostic and prognostic targets for BC patients.https://doi.org/10.1002/cam4.4545bioinformaticsbreast cancerdiagnosisoncogenesisprognosis |
| spellingShingle | Xingxing Dong Yalong Yang Gaoran Xu Zelin Tian Qian Yang Yan Gong Gaosong Wu The initial expression alterations occurring to transcription factors during the formation of breast cancer: Evidence from bioinformatics Cancer Medicine bioinformatics breast cancer diagnosis oncogenesis prognosis |
| title | The initial expression alterations occurring to transcription factors during the formation of breast cancer: Evidence from bioinformatics |
| title_full | The initial expression alterations occurring to transcription factors during the formation of breast cancer: Evidence from bioinformatics |
| title_fullStr | The initial expression alterations occurring to transcription factors during the formation of breast cancer: Evidence from bioinformatics |
| title_full_unstemmed | The initial expression alterations occurring to transcription factors during the formation of breast cancer: Evidence from bioinformatics |
| title_short | The initial expression alterations occurring to transcription factors during the formation of breast cancer: Evidence from bioinformatics |
| title_sort | initial expression alterations occurring to transcription factors during the formation of breast cancer evidence from bioinformatics |
| topic | bioinformatics breast cancer diagnosis oncogenesis prognosis |
| url | https://doi.org/10.1002/cam4.4545 |
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