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

Abstract：

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.

journal_name

J Hepatobiliary Pancreat Sci

journal_title

Journal of hepato-biliary-pancreatic sciences

authors

Teraoku H,Morine Y,Ikemoto T,Saito Y,Yamada S,Yoshikawa M,Takasu C,Higashijima J,Imura S,Shimada M

doi

10.1002/jhbp.376

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

565-73

issue

9

eissn

1868-6974

issn

1868-6982

journal_volume

23

pub_type

杂志文章

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