Premium
Role of thrombospondin‐1 expression in colorectal liver metastasis and its molecular mechanism
Author(s) -
Teraoku Hiroki,
Morine Yuji,
Ikemoto Tetsuya,
Saito Yu,
Yamada Shinichiro,
Yoshikawa Masato,
Takasu Chie,
Higashijima Jun,
Imura Satoru,
Shimada Mitsuo
Publication year - 2016
Publication title -
journal of hepato‐biliary‐pancreatic sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 1868-6974
DOI - 10.1002/jhbp.376
Subject(s) - thrombospondin 1 , expression (computer science) , angiogenesis , medicine , computer science , programming language
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.