Clinical Characterization and Prognostic Value of TPM4 and Its Correlation with Epithelial–Mesenchymal Transition in Glioma

Abstract

Tropomyosin 4 (TPM4) has been reported as an oncogenic gene across different malignancies. However, the role of TPM4 in glioma remains unclear. This study aimed to determine the clinical characterization and prognostic value of TPM4 in gliomas. Transcriptome expression and clinical information were collected from the CGGA and TCGA datasets, which included 998 glioma patients. ScRNA-seq data were obtained from CGGA. R software was utilized for statistical analyses. There was a positive correlation between TPM4 and WHO grades. IDH-wildtype and mesenchymal subtype gliomas were accompanied by TPM4 upregulation. GO and GSEA analysis suggested that TPM4 was profoundly associated with epithelial-to-mesenchymal transition (EMT). Subsequent GSVA revealed a robust correlation between TPM4 and three signaling pathways of EMT (hypoxia, TGF-β, PI3K/AKT). Furthermore, TPM4 showed a synergistic effect with mesenchymal biomarkers, particularly with N-cadherin, Slug, Snail, TWIST1, and vimentin. ScRNA-seq analysis suggested that higher TPM4 was mainly attributed to tumor cells and macrophages and associated with tumor cell progression and macrophage polarization. Finally, high TPM4 was significantly associated with unfavorable outcomes. In conclusion, our findings indicate that TPM4 is significantly correlated with more malignant characteristics of gliomas, potentially through involvement in EMT. TPM4 could predict worse survival for patients with glioma.

Integrated pan-cancer analysis and experimental verification of the roles of tropomyosin 4 in gastric cancer

“…There are four tropomyosin (TPM) genes, namely TPM1, TPM2, TPM3, and TPM4, in mammals. In recent years, the abnormal expression of TPM4 was investigated in multiple malignancies, invasive breast cancer ( 7 ), colon cancer ( 8 ), glioma ( 9 ), hepatocellular carcinoma ( 10 ), lung cancer ( 11 ), and ovarian cancer ( 12 ). TPM4 is a crucial intermediary in different human malignancies, but the association between the function of TPM4 and GC is currently unclear.…”

“…TPM4 expression is of clinical significance, has prognostic value, and is related to immune infiltration in pancreatic cancer ( 14 ). TPM4 is upregulated and related to the malignant characteristics of gliomas, possibly via epithelial-mesenchymal transition ( 9 ). In our previous study, TPM4 was found to function as an oncogene that stimulates the proliferation of cells and prevents the death of cells by apoptosis both in vitro and in vivo .…”

Editorial: Frontiers in Neuro Oncology and Neurosurgery

“…Wang et al studied the role of Tropomyosin 4 (TPM4) (an oncogenic gene known to be involved in many malignancies) in 998 glioma patients and suggest that TPM4 is significantly correlated with more malignant characteristics of gliomas, potentially through involvement in epithelial-to-mesenchymal transition with a worse prognosis. It is an original and elegant study on a great number of patients [ 13 ].…”