CD147 Expression Is Associated with Tumor Proliferation in Bladder Cancer via GSDMD

Abstract

Purpose: CD147, also known as BSG, is a type I transmembrane glycoprotein that belonged to immunoglobulin superfamily. Mature CD147 is an N-linked glycosylated protein and exists on the transmembrane and as soluble forms in tumors. However, the function of CD147 in cell proliferation of bladder cancer (BC) remains to be elucidated.

Methods: The study included 159 patients with BC and 68 healthy controls. The expression of CD147 and gasdermin D (GSDMD) was analyzed by immunohistochemistry (IHC). Western blotting was performed to detect the expression of proteins in BC cells. The relationship between CD147 and GSDMD was analyzed by the IHC score.

Results: The expression of CD147 was significantly increased in BC when compared to healthy controls, and the level of CD147 was correlated with tumor proliferation characterized by Ki-67, which is a cell proliferation antigen. In addition, CD147 treatment of BC cells increased the expression of GSDMD, leading to increased Ki-67 expression, while CD147 blockade with peptide in BC significantly reduced GSDMD expression, resulting in reduced cell proliferation. Furthermore, overexpression of GSDMD markedly overcame the inhibitory effect of CD147 peptide on tumor proliferation. BC patients with overexpression of CD147 showed correlation with GSDMD and demonstrated significantly poorer prognosis and overall survival rate.

Conclusion: These findings suggested that high expression of CD147 contributed to tumor proliferation in BC via GSDMD, which might in turn act as an unfavorable prognostic marker.

Figure 1

IHC analysis of CD147 and Ki-67 expression in bladder cancer. (a, d) IHC was performed to detect CD147 and Ki-67 expression in clinical sample from bladder cancer and healthy control. Scale bar, 50 m. (b–e) Statistical analysis of mean density of CD147 expression in the indicated group by t-test, ^∗∗p < 0.01. (f) Clinical association analysis was performed between CD147 and GSDMD.

Figure 2

CD147 regulates GSDMD expression in BC. (a) IHC was used to analyze CD147 and GSDMD expression in various stages of bladder cancer tissue, and (b, c) WB was performed to detect the effect of CD147 on GSDMD and Ki-67 expression in the indicated group. (d) CCK-8 assay was employed to detect cell proliferation in the indicated group. (e) TCGA analysis of positive association between CD147 and GSDMD.

Figure 3

CD147 is a worse prognostic factor for mortality in BC patients. a and b represent the Kaplan–Meier analysis of DFS (a) and OS (b) in BC patients according to CD147 expression from TCGA dataset. (c) Survival rate was analyzed in 159 subjects classified into two groups based on CD147 expression, p=0.041.