TRPM2 expression levels are associated with histological grading in patients with tongue squamous cell carcinoma.

Abstract

Tongue squamous cell carcinoma (TSCC) accounts for a large proportion of cases of head and neck cancer. Transient receptor potential melastatin 2 (TRPM2) is a non‑selective cation channel sensitive to oxidative stress. High TRPM2 expression has been reported in various types of cancer, including neuroblastoma, glioblastoma, non‑small cell lung cancer and breast cancer. However, whether expression levels of TRPM2 are associated with aggressive clinical features in TSCC remains unclear. A total of 26 clinical sample tissues with TSCC were collected in the present study. The expression levels of the TRPM2 channel were determined by immunohistochemistry, western blot, and qPCR analysis. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured to reveal oxidative stress levels in TSCC tissues with different degrees of differentiation. The protein expression levels of caspase‑8, Bcl‑xL, Bax, caspase‑9, cleaved caspase‑9, caspase‑3, cleaved caspase‑3, poly [ADP‑ribose] polymerase (PARP) and cleaved PARP were detected by western blot analysis. Analysis of the tissue specimens from 26patients with TSCC showed that TRPM2 was not upregulated in all specimens. Notably, the expression levels of TRPM2 were associated with the histological grading of different tissues. The specimens with low TRPM2 expression were significantly associated with moderate or poor differentiation (P=0.003), and exhibited increased lipid peroxidation level and decreased SOD activity. Furthermore, the altered expression of pro‑ and anti‑apoptotic proteins indicated a significant upregulation of apoptosis in TSCC tissues with low TRPM2 expression. These results suggested that low TRPM2 expression in TSCC may inhibit the ability of cells to adapt to or resist the oxidative stress, resulting in increased susceptibility to apoptosis. Therefore, the oxidative stress‑sensitive TRPM2 channel may serve as a potent biomarker, and the present study provides insights into the underlying mechanisms of tumor cell differentiation.