A pan-cancer analysis reveals the genetic alterations and immunotherapy of Piezo2 in human cancer

Abstract

Background: Piezo2 is a transmembrane-spanning ion channel protein implicated in multiple physiological processes, including cell proliferation and angiogenesis in many cell types. However, Piezo2 was recognized as representing a double-edged sword in terms of tumor growth. The prognostic and immunotherapeutic roles of Piezo2 in pan-cancer have not been reported.Methods: In this study, several databases available including the UCSC Xena database, HPA, TIDE, GSEA, and cBioportal were used to investigate the expression, alterations, associations with immune indicators, and prognostic roles of Piezo2 across pan-cancer. R software and Perl scripts were used to process the raw data acquired from the UCSC Xena database.Results: Based on processed data, our results suggested that Piezo2 expression levels were tissue-dependent in different tumor tissues. Meanwhile, the survival analysis reflected that patients suffering from KIRC, LUAD, and USC with high Piezo2 expression had good OS, while those suffering from KIRP and SARC with high Piezo2 expression had poor OS. In addition, our results showed that Piezo2 expression was associated with the infiltration of CD4+ T memory cells, mast cells, and dendritic cells. These results suggested that Piezo2 may involve tumor progression by influencing immune infiltration or regulating immune cell function. Further analysis indicated that Piezo2 could influence TME by regulating T-cell dysfunction. We also found that gene mutation was the most common genetic alteration of Piezo2. The GSEA analysis revealed that Piezo2 was associated with calcium ion transport, the activation of the immune response, antigen processing and presentation pathways.Conclusion: Our study showed the expression and prognostic features of Piezo2 and highlighted its associations with genetic alterations and immune signatures in pan-cancer. Moreover, we provided several novel insights for further research on the therapeutic potential of Piezo2.

Roles of mechanosensitive ion channels in immune cells

“…Limited research has been conducted on their functions in immune cells and their associations with disease. A pan-cancer analysis revealed that Piezo2 is associated with T-cell dysfunction and the secretion of immune-related factors, with the precise mechanism requiring further clarification [ 53 ].…”

Mechanosensitive Ion Channels: Their Physiological Importance and Potential Key Role in Cancer

“…Last year, an extensive in silico analysis of Piezo2 expression, genetic relationships with immunological markers, and predictive functions in pan-cancer was performed. This study indicated that Piezo2 expression is cell- and tissue-dependent in different cancer types and is related to prognosis in several tumors [ 132 ].…”

The relationship between tumor infiltrating immune cells and the prognosis of patients with lung adenocarcinoma

“…Moreover, the 5-year survival rate of patients with advanced lung carcinoma has increased to 16% (5). The PACIFIC study suggested that immune maintenance therapy after radical concurrent chemoradiotherapy for stage III inoperable locally advanced NSCLC can significantly improve the survival of patients, and it has become the standard treatment recommended by the guidelines (6). Also, the application of immune checkpoint inhibitors can achieve sustained and effective remission in lung cancer, melanoma, bladder urothelial carcinoma, and Hodgkin's lymphoma (7), and patients can survive for a long time.…”