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

Background/Purpose
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 labelling index (Ki-67 LI), expression of other relevant molecules, and microvessel density (MVD) investigated.
Results
THBS1 low expression correlated with more advanced grade of liver and lymph node metastases and significantly worse overall survival than strong THBS1 expression (3-year survival: 96.7% vs. 65.4%, p<0.01). Multivariate analysis identified THBS1 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.

内容要旨・審査要旨・論文本文の公開
本論文は, 著者Hiroki Teraokuの学位論文として提出され, 学位審査・授与の対象となっている。