Poole, R.A.; Wang, Q.; Ray, A.; Takabe, K.; Opyrchal, M.; Katsuta, E. Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients. Cancers2024, 16, 683.
Poole, R.A.; Wang, Q.; Ray, A.; Takabe, K.; Opyrchal, M.; Katsuta, E. Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients. Cancers 2024, 16, 683.
Poole, R.A.; Wang, Q.; Ray, A.; Takabe, K.; Opyrchal, M.; Katsuta, E. Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients. Cancers2024, 16, 683.
Poole, R.A.; Wang, Q.; Ray, A.; Takabe, K.; Opyrchal, M.; Katsuta, E. Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients. Cancers 2024, 16, 683.
Abstract
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. 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 analyzed immune cell levels in breast tumors from TCGA through a CIBERSORT algorithm. Our results demonstrated that PIEZO1 expression levels are higher in hormone receptor (HR) negative than HR positive cohorts. High PIEZO1 expression is correlated with a significant decrease in survival in HR negative cohorts, 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.
Keywords
ion channels; hormone receptor negative breast cancer; PIEZO; mechano-signaling
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
