Role of thrombospondin-1 expression in colorectal liver metastasis and its molecular mechanism.

Background: Thrombospondin‐1 (THBS‐1), a glycoprotein, is an endogenous inhibitor of angiogenesis and tumor growth. In this study, we investigated the clinical role and mechanism of THBS‐1 expression in colorectal liver metastases, focusing on the relationships between its expression and tumor growth, epithelial‐mesenchymal transition (EMT), and expression of other relevant molecules. Methods: Ninety‐four patients who initially underwent curative hepatic resection were enrolled in this study and correlations between expression of THBS‐1 (THBS‐1 high [n = 35] and THBS‐1 low [n = 59]) and tumor growth, Ki‐67 labeling index (Ki‐67 LI), expression of other relevant molecules, and microvessel density (MVD) investigated. Results: THBS‐1 low expression correlated with more advanced grade of liver and lymph node metastases and significantly worse overall survival than strong THBS‐1 expression (3‐year survival: 96.7% vs. 65.4%, P < 0.01). Multivariate analysis identified THBS‐1 low expression as an independent prognostic factor (HR 2.82, 95% CI 1.21–7.71, P = 0.01). THBS‐1 low expression correlated positively with high Ki‐67 LI (P < 0.05) and inversely with E‐cadherin (P < 0.05) and hypoxia inducible factor‐1α (HIF‐1α) expression (P < 0.05); THBS‐1 expression and MVD were not significantly correlated. Conclusions: Low THBS‐1 expression may be an independent poor prognostic factor that affects tumor growth and EMT acquisition. Additionally, THBS‐1 may be regulated by the HIF‐1 pathway. Highlight Setting out to investigate the clinical role and mechanism of thrombospondin‐1 expression in colorectal liver metastases, Teraoku and colleagues revealed that low thrombospondin‐1 expression may be an independent poor prognostic factor that affects tumor growth and epithelial–mesenchymal transition acquisition and may be regulated by the hypoxia inducible factor‐1 pathway. [ABSTRACT FROM AUTHOR]