Abstract
In multiple solid tumours, including gliomas, the mechanical properties change as the disease progresses. If and how mechanical cues regulate tumour cell proliferation is currently not fully studied. PIEZO1 has recently been identified as a crucial mechanosensitive cation channel in multiple solid tumours. However, we didn’t find any clinical data describing the association between PIEZO1 expression and glioma. To investigate the role of PIEZO1 in gliomas, we analysed PIEZO1 gene expression at the transcriptome level, genomic profiles and the association of PIEZO1 with clinical practice. In total, 1633 glioma samples with transcriptome data, including data from the Chinese Glioma Genome Atlas RNAseq, the Cancer Genome Atlas RNAseq and GSE16011 databases, were included in this study. Clinical information and genomic profiles including somatic mutations were also obtained. We found that PIEZO1 expression was highly correlated with malignant clinical and molecular subtypes of glioma. Gene ontology analysis showed that expression of PIEZO1 was correlated with tumour microenvironment-related genes that encode proteins involved in extracellular matrix (ECM) organization, angiogenesis and cell migration. Additionally, PIEZO1 was shown to be involved in tumour progression by serving as the central checkpoint of multiple ECM remodelling-related signalling pathways to modulate tumour cell proliferation and the tumour microenvironment in turn. Finally, high PIEZO1 expression was correlated with reduced survival time and acted as a robust biomarker for poor prognosis in gliomas. Taken together, the results indicated that high PIEZO1 expression is closely associated with highly malignant gliomas. Importantly, PIEZO1 serves as a key factor involved in sensing mechanical properties in the tumour and can regulate both tumour cells and their microenvironment to promote glioma progression, and it is also a potential therapeutic target for the treatment of gliomas.
Highlights
In multiple solid tumours, including gliomas, the mechanical properties change as the disease progresses
The IDH mutation status detection method was described in Guan et al.22. mRNAseq data obtained from 1032 WHO grade II to grade IV gliomas were downloaded from The Cancer Genome Atlas (TCGA)
Mechanical cues play a critical role in tumour progression and in shaping the tumour microenvironment (TME) by regulating both tumour cells and the TME
Summary
In multiple solid tumours, including gliomas, the mechanical properties change as the disease progresses. Gene ontology analysis showed that expression of PIEZO1 was correlated with tumour microenvironment-related genes that encode proteins involved in extracellular matrix (ECM) organization, angiogenesis and cell migration. PIEZO1 serves as a key factor involved in sensing mechanical properties in the tumour and can regulate both tumour cells and their microenvironment to promote glioma progression, and it is a potential therapeutic target for the treatment of gliomas. Tumour cells sense mechanical stimuli such as tissue pressure (stiffness), cell membrane tension, shear stress, and tissue pressure from the extracellular matrix (ECM) These mechanical cues are transduced into biochemical signals to modulate both tumour cells and the TME, promoting cancer progression[4]. These processes strongly depend on mechanosensitive ion channels. Until now, the relationship between PIEZO1 expression and glioma malignancy in human patients has not been studied
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