title: Clinical significance of osteoprotegerin expression in human colorectal cancer.
abstract: OBJECTIVE
  This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC).
  
  
  METHODS
  The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells, especially in patients with distant metastases, was a prerequisite to select candidate genes. The mRNA expression of candidate genes was investigated by quantitative reverse transcriptase PCR (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study and investigated the relationship between protein expression and clinicopathologic features in 274 CRC patients.
  
  
  RESULTS
  Using microarray analysis, we identified 6 candidate genes related to distant metastases in CRC patients. Among these genes, osteoprotegerin (OPG) is known to be associated with aggressiveness in several cancers through inhibition of apoptosis via neutralization of the function of TNF-related apoptosis-inducing ligand. The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastases than those without metastases. Overexpression of OPG protein was associated with significantly worse overall survival and relapse-free survival. Moreover, overexpression of the OPG protein was an independent risk factor for CRC recurrence.
  
  
  CONCLUSIONS
  Overexpression of OPG may be a predictive biomarker of CRC recurrence and a target for treatment of this disease.
authors.affiliation: Departments of Surgical Oncology and Translational Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tsukamoto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Iida
authors.forename: Megumi
authors.initials: M
authors.lastname: Ishiguro
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizushima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uetake
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis; D053244:Osteoprotegerin / Q000235:genetics* / Q000378:metabolism; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D053244:Osteoprotegerin