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.
PIEZO1作为机械敏感性离子通道在人体中发挥着关键作用。研究表明该通道在组织发育及多种重要生理过程调控中具有重要意义。现有证据显示PIEZO1离子通道参与癌症侵袭与进展过程：其表达水平升高与乳腺癌细胞迁移能力增强、胃癌细胞化疗耐药及侵袭性提升、骨肉瘤细胞侵袭性增加密切相关。此外，胶质瘤患者中高表达的PIEZO1与不良预后显著相关。然而在肺癌研究中，高PIEZO1水平却与较好临床结局相关。目前PIEZO1在乳腺癌中的临床意义尚未明确，因此本研究旨在揭示PIEZO1在乳腺癌中的临床相关性。 通过分析癌症基因组图谱（TCGA）乳腺癌数据，我们检测了PIEZO1表达水平及其与生存期的相关性，并在独立数据集GSE3494中进行验证。同时进行基因集富集分析（GSEA）和通路富集分析，并采用CIBERSORT算法解析TCGA乳腺癌样本的免疫细胞组成。研究结果显示：激素受体（HR）阴性组中PIEZO1表达水平显著高于HR阳性组；高PIEZO1表达与HR阴性组（特别是三阴性乳腺癌）生存期显著缩短相关，提示其可作为HR阴性乳腺癌的预后生物标志物。GSEA分析表明，高PIEZO1表达的HR阴性肿瘤中富集了上皮-间质转化（EMT）、缺氧及多条信号通路等与侵袭表型和治疗抵抗相关的信号通路。同时发现高PIEZO1表达的HR阴性肿瘤中CD8+和CD4+ T细胞浸润显著减少。未来需进一步研究以阐明PIEZO1在HR阴性乳腺癌中的机制作用。
肿瘤(癌症)患者之家