Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients
PIEZO1 plays a crucial role in the human body as a mechanosensory ion channel. It has been demonstrated that PIEZO1 is important in tissue development and regulating many essential physiological processes. Studies have suggested that the PIEZO1 ion channel plays a role in invasion and progression in...
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| Format: | Article |
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MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/4/683 |
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| author | Rylee Ann Poole Qingfei Wang Alo Ray Kazuaki Takabe Mateusz Opyrchal Eriko Katsuta |
| author_facet | Rylee Ann Poole Qingfei Wang Alo Ray Kazuaki Takabe Mateusz Opyrchal Eriko Katsuta |
| author_sort | Rylee Ann Poole |
| collection | DOAJ |
| description | PIEZO1 plays a crucial role in the human body as a mechanosensory ion channel. It has been demonstrated that PIEZO1 is important in tissue development and regulating many essential physiological processes. Studies have suggested that the PIEZO1 ion channel plays a role in invasion and progression in cancer; elevated levels of PIEZO1 have been correlated with increased migration in breast cancer cells, chemo-resistance and invasion in gastric cancer cells, and increased invasion of osteosarcoma cells. In addition, high PIEZO1 expression levels were correlated with a worse prognosis in glioma patients. On the other hand, studies in lung cancer have attributed high PIEZO1 levels to better patient outcomes. However, the clinical impact of PIEZO1 in breast cancer is not well characterized. Therefore, our goal was to determine the clinical relevance of PIEZO1 in breast cancer. An analysis of breast cancer data from The Cancer Genome Atlas (TCGA) was conducted to investigate PIEZO1 expression levels and correlation to survival, followed by validation in an independent dataset, GSE3494. We also performed gene set enrichment analysis (GSEA) and pathway enrichment analysis. We also analyzed the immune cell composition in breast tumors from TCGA through a CIBERSORT algorithm. Our results demonstrated that the PIEZO1 expression levels are higher in hormone-receptor (HR)-negative than in HR-positive cohorts. High PIEZO1 expression is correlated with a significant decrease in survival in HR-negative cohorts, especially in triple-negative breast cancer (TNBC), suggesting that PIEZO1 could be utilized as a prognostic biomarker in HR-negative breast cancer. GSEA showed that various signaling pathways associated with more invasive phenotypes and resistance to treatments, including epithelial–mesenchymal transition (EMT), hypoxia, and multiple signaling pathways, are enriched in high-PIEZO1 HR-negative tumors. Our results also demonstrated a decrease in CD8+ and CD4+ T cell infiltration in high-PIEZO1 HR-negative tumors. Further investigations are necessary to elucidate the mechanistic roles of PIEZO1 in HR-negative breast cancer. |
| first_indexed | 2024-03-07T22:38:58Z |
| format | Article |
| id | doaj.art-b3ebf740e92043bbb744a0dc1c191560 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-07T22:38:58Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b3ebf740e92043bbb744a0dc1c1915602024-02-23T15:10:35ZengMDPI AGCancers2072-66942024-02-0116468310.3390/cancers16040683Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer PatientsRylee Ann Poole0Qingfei Wang1Alo Ray2Kazuaki Takabe3Mateusz Opyrchal4Eriko Katsuta5Division of Hematology/Oncology, Indiana University, Indianapolis, IN 46202, USADivision of Hematology/Oncology, Indiana University, Indianapolis, IN 46202, USADivision of Hematology/Oncology, Indiana University, Indianapolis, IN 46202, USADepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USADivision of Hematology/Oncology, Indiana University, Indianapolis, IN 46202, USADepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USAPIEZO1 plays a crucial role in the human body as a mechanosensory ion channel. It has been demonstrated that PIEZO1 is important in tissue development and regulating many essential physiological processes. Studies have suggested that the PIEZO1 ion channel plays a role in invasion and progression in cancer; elevated levels of PIEZO1 have been correlated with increased migration in breast cancer cells, chemo-resistance and invasion in gastric cancer cells, and increased invasion of osteosarcoma cells. In addition, high PIEZO1 expression levels were correlated with a worse prognosis in glioma patients. On the other hand, studies in lung cancer have attributed high PIEZO1 levels to better patient outcomes. However, the clinical impact of PIEZO1 in breast cancer is not well characterized. Therefore, our goal was to determine the clinical relevance of PIEZO1 in breast cancer. An analysis of breast cancer data from The Cancer Genome Atlas (TCGA) was conducted to investigate PIEZO1 expression levels and correlation to survival, followed by validation in an independent dataset, GSE3494. We also performed gene set enrichment analysis (GSEA) and pathway enrichment analysis. We also analyzed the immune cell composition in breast tumors from TCGA through a CIBERSORT algorithm. Our results demonstrated that the PIEZO1 expression levels are higher in hormone-receptor (HR)-negative than in HR-positive cohorts. High PIEZO1 expression is correlated with a significant decrease in survival in HR-negative cohorts, especially in triple-negative breast cancer (TNBC), suggesting that PIEZO1 could be utilized as a prognostic biomarker in HR-negative breast cancer. GSEA showed that various signaling pathways associated with more invasive phenotypes and resistance to treatments, including epithelial–mesenchymal transition (EMT), hypoxia, and multiple signaling pathways, are enriched in high-PIEZO1 HR-negative tumors. Our results also demonstrated a decrease in CD8+ and CD4+ T cell infiltration in high-PIEZO1 HR-negative tumors. Further investigations are necessary to elucidate the mechanistic roles of PIEZO1 in HR-negative breast cancer.https://www.mdpi.com/2072-6694/16/4/683ion channelshormone-receptor-negative breast cancerPIEZOmechano-signaling |
| spellingShingle | Rylee Ann Poole Qingfei Wang Alo Ray Kazuaki Takabe Mateusz Opyrchal Eriko Katsuta Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients Cancers ion channels hormone-receptor-negative breast cancer PIEZO mechano-signaling |
| title | Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients |
| title_full | Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients |
| title_fullStr | Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients |
| title_full_unstemmed | Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients |
| title_short | Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients |
| title_sort | increased piezo1 expression is associated with worse clinical outcomes in hormone receptor negative breast cancer patients |
| topic | ion channels hormone-receptor-negative breast cancer PIEZO mechano-signaling |
| url | https://www.mdpi.com/2072-6694/16/4/683 |
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