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Down-regulation of osteoprotegerin expression as a novel biomarker for colorectal carcinoma

Other Titles
 대장암에서 osteoprotegerin 발현의 조절 기전 및 임상적 의의 
 Hyun-Soo Kim  ;  Gun Yoon  ;  Sung-Im Do  ;  Sung-Joo Kim  ;  Youn-Wha Kim 
 ONCOTARGET , Vol.7(12) : 15187-15199, 2016 
Journal Title
Issue Date
Apoptosis ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism* ; Cell Proliferation ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology* ; DNA Methylation ; Epigenesis, Genetic ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic* ; Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Liver Neoplasms/secondary* ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/metabolism ; Neoplasm Recurrence, Local/pathology* ; Osteoprotegerin/genetics ; Osteoprotegerin/metabolism* ; Prognosis ; Promoter Regions, Genetic ; Tumor Cells, Cultured
colorectal carcinoma ; down-regulation ; osteoprotegerin ; promoter methylation
A better understanding of tumor biology is important in the identification of molecules that are down-regulated in malignancy and in determining their role in tumor suppression. The aim of this study was to analyze osteoprotegerin (OPG) expression in colorectal carcinoma (CRC) and to investigate the underlying mechanism for changes in the expression of OPG. OPG expression was assessed in CRC tissue samples and cell lines. The methylation status of the OPG promoter region was determined, and the effects of demethylation on OPG expression were analyzed. The effects of recombinant OPG (rOPG) administration on cellular functions were also investigated. Clinical and prognostic implications of OPG protein expression in CRC patients were analyzed. The CRC tissues and cells showed significantly lower OPG expression. Pyrosequencing of OPG-silenced CRC cells revealed that the OPG gene promoter was highly methylated. Treatment with demethylating agent significantly elevated OPG mRNA and protein expression. rOPG significantly decreased cell viability and MMP-2 and VEGF-A production in CRC cells. Reduced OPG immunoreactivity was associated with aggressive oncogenic behavior in CRC. Also, OPG expression was found to be an independent predictor of recurrent hepatic metastasis and independent prognostic factor for worse survival rates. We demonstrated that OPG silencing in CRC occurs through epigenetic repression, and is involved in the development and progression of CRC. Our data suggest that OPG is a novel prognostic biomarker and a new therapeutic target for the treatment of patients with CRC.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyun-Soo(김현수)
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