title: CD93 gene polymorphism is associated with disseminated colorectal cancer.
abstract: OBJECTIVE
  Cluster of differentiation 93 (CD93) is involved in apoptosis and inflammation and has a suggested role in angiogenesis, and all of which are involved in the development and dissemination of cancer. We evaluated the expression of CD93 and the association with two single nucleotide polymorphisms (SNPs), rs2749812 and rs2749817, as possible biomarkers in colorectal cancer (CRC).
  
  
  METHODS
  Tissue levels and plasma levels of CD93 were measured using an enzyme-linked immunosorbent assay (ELISA). Expression of CD93 was determined by immunohistochemistry, western blot and gene expression analysis. Genotype frequencies were established for the SNPs by real-time polymerase chain reaction (PCR), and the association with tumour stage and survival was analysed.
  
  
  RESULTS
  Total CD93 levels were 82% higher (P < 0.001) in tumours compared to matched normal tissues. Mean levels of soluble CD93 in plasma were 30% lower (P < 0.001) in the patients compared to the controls. The T/T genotype of SNP rs2749817 was more common in stage IV patients, with consequently higher risk of CRC death (T/T vs. C/C and C/T; hazard ratio (HR) = 1.73, 95% confidence interval (CI) = 1.11-2.67, P = 0.014), and was associated with a higher risk of CRC recurrence after radical operation (T/T vs. C/C and C/T; HR = 2.07, CI = 1.22-3.51, P = 0.007).
  
  
  CONCLUSIONS
  We showed that the T/T genotype of SNP rs2749817 is associated with disseminated cancer at diagnosis and an increased recurrence rate after radical operation. Patients with this genotype may benefit from early identification.
authors.affiliation: Division of Drug Research, Department of Medical and Health Sciences, Faculty of Health Sciences, University of Linköping, 58185, Linköping, Sweden, renate.slind.olsen@rjl.se.
authors.forename: Renate S
authors.initials: RS
authors.lastname: Olsen
authors.forename: Mikael
authors.initials: M
authors.lastname: Lindh
authors.forename: Emina
authors.initials: E
authors.lastname: Vorkapic
authors.forename: Roland E
authors.initials: RE
authors.lastname: Andersson
authors.forename: Niklas
authors.initials: N
authors.lastname: Zar
authors.forename: Sture
authors.initials: S
authors.lastname: Löfgren
authors.forename: Jan
authors.initials: J
authors.lastname: Dimberg
authors.forename: Andreas
authors.initials: A
authors.lastname: Matussek
authors.forename: Dick
authors.initials: D
authors.lastname: Wågsäter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011951:Receptors, Complement / Q000097:blood / Q000235:genetics*; D012995:Solubility
chemical_list: D008562:Membrane Glycoproteins; D011951:Receptors, Complement; C032402:complement 1q receptor