Assessment of gastric cancer malignancy based on CD133 and thrombospondin1 (THBS1) expression and the role of histone acetylation.

Abstract

31 Background: Epigenetic modification by HDAC (histone deacetylase) plays important roles in the development and progression of cancer. It has been reported that CD133 positive cancer stem cells were induced through the HDAC → HIF-1α (Hypoxia Inducible Factor-1α) pathway, and Thrombospondin1 (THBS1) is associated with tumor angiogenesis. The aim of this study is to evaluate relationship between the HDAC, CD133, THBS1 and prognosis in gastric cancer. Methods: 65 patients of gastric cancer were enrolled in this study. HDAC1, CD133 and THBS1 expressions were evaluated in immunohistochemical (IHC) staining of surgical specimens. Relationship between the expressions of HDAC1, CD133, THBS1 and clinicopathological factors was investigated. Results: HDAC1-positive patients were 52% and had significantly poor prognosis compared with negative patients. There were more frequent liver metastasis and lymphatic invasion in positive patients. CD133-positive patients were 23.1% and had significantly poor prognosis compared with negative patients. There were more frequent depth wall invasion, distant metastasis, peritoneal recurrence. THBS1-positive patients were 26% and had significantly better prognosis compared with negative patients. In THBS1 positive patients, there was less lymph node metastasis, positive peritoneal cytology in ascites, distant metastasis and lymphatic invasion. CD133 expression is positively correlated with HDAC1. THBS1 expression revealed negative correlation with HDAC1. The survival rate of HDAC1 (+) / CD133 (+) group was significantly poor prognosis compared to the other group (HDAC1 (+) / CD133 (-), HDAC1 (-) / CD133 (+), HDAC1 (-) / CD133 (-)). HDAC1 (-) / THBS1 (+) group revealed significantly higher survival rate compared to the other group (HDAC1 (-) / THBS1 (+), HDAC1 (+) / THBS1 (+), HDAC1 (+) / THBS1 (-)). Conclusions: It was suggested that HDAC1 promoted CD133, suppressed THBS1 in gastric cancer and their interaction were increased the degree of malignancy.