title: Tumor location determines midkine level and its association with the disease progression in colorectal cancer patients: a pilot study.
abstract: OBJECTIVE
  The purpose of this study was to evaluate midkine, multipotential cytokine, and growth factor in colorectal cancer (CRC) stratified by tumor location.
  
  
  METHODS
  Midkine was assessed immunoenzymatically in paired cancerous and noncancerous tissues from 53 CRCs and referred to CRC stage, tumor location, and size, and circulating cytokine levels.
  
  
  RESULTS
  Midkine was higher in cancerous versus noncancerous tissue in 98 % cases (424.2 vs. 31.1 pg/mg, p < 0.0001). Mean fold increase was 30.1; in 72.5 %, the relative increase was over fivefold. Midkine upregulation was more pronounced in colon than in rectum (fold increase: 36.6 vs. 12.7, p = 0.005) due to higher midkine level in noncancerous rectal than colonic tissue (45.5 vs. 26.2 pg/mg, p = 0.074). Tumor location affected midkine association with CRC stage. Midkine fold change was higher in advanced stages of rectal cancers (16.8 vs. 5.3, respectively in III/IV vs. I/II, p = 0.013), while it tended to be lower in colonic ones (25.3 vs. 47.8, p = 0.134). In addition, fold change in midkine level was higher in rectal N1 than N0 cancers (17.3 vs. 16.5, p = 0.032), while it tended to be lower in colonic cancers (23.6 vs. 50.1, p = 0.085). Midkine negatively correlated with tumor size (r = 0.40, p = 0.017), while it tended to positively correlate with its serum levels (r = 0.45, p = 0.081).
  
  
  CONCLUSIONS
  Midkine is differently expressed in tumors arising from colonic and rectal mucosa, where it may play diverse roles in carcinogenesis. High midkine expression in noncancerous rectal mucosa might contribute to, a characteristic for rectal cancers, higher incidence of local recurrence. Divergent expression of midkine and its association pattern ought to be taken into account while designing midkine-directed therapies for CRC.
authors.affiliation: Department of Medical Biochemistry, Wroclaw Medical University, ul. Chalubinskiego 10, Wroclaw, Poland. malgorzata.krzystek-korpacka@am.wroc.pl
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krzystek-Korpacka
authors.forename: Dorota
authors.initials: D
authors.lastname: Diakowska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Grabowski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Gamian
mesh_terms: D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D000078792:Midkine; D010865:Pilot Projects; D047368:Tumor Burden
chemical_list: D016207:Cytokines; D000078792:Midkine