title: CXCL5, a promoter of cell proliferation, migration and invasion, is a novel serum prognostic marker in patients with colorectal cancer.
abstract: OBJECTIVE
  Serum CXCL5 levels in patients with colorectal cancer (CRC) were assessed to evaluate correlation with clinicopathologic features and prognosis. The effects of CXCL5 on CRC cells were also investigated in vitro.
  
  
  METHODS
  Based on cytokine array analysis, CXCL5 was identified as a novel prognostic serum marker. Serum levels of CXCL5 were assessed in 250 CRC patients and 33 normal volunteers by enzyme-linked immunosorbent assay (ELISA), and their relation to clinicopathologic findings and survival investigated. CXCL5 levels in CRC cell lines were also measured by ELISA, and CXCL5 and CXCR2 expression was evaluated by immunohistochemistry. To investigate the biological role of the CXCL5/CXCR2 axis, recombinant human CXCL5 and CXCR2 neutralisation antibodies were used for proliferation, migration and invasion assays.
  
  
  RESULTS
  Preoperative serum CXCL5 was significantly elevated in patients with CRC compared with healthy volunteers (p=0.013). High serum CXCL5 was significantly associated with female sex (p=0.0098) and liver metastasis (p=0.0040). Univariate analysis correlated elevated CXCL5 with poor overall survival (p=0.0002). Multivariate analysis showed that elevated CXCL5 was a significant and independent prognostic factor of survival in all CRC patients (p=0.038). CRC cells secreted CXCL5, and administration of recombinant human CXCL5 promoted proliferation, migration and partial invasion. These effects were generally inhibited by CXCR2 neutralisation antibody.
  
  
  CONCLUSIONS
  Preoperative serum CXCL5 could serve as a novel predictive marker for prognosis determination of CRC patients. CXCL5/CXCR2 axis might be associated with colorectal cancer progression.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Kawamura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Kouji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.forename: Junichiro
authors.initials: J
authors.lastname: Hiro
authors.forename: Keiichi
authors.initials: K
authors.lastname: Uchida
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000097:blood*; D018938:Caco-2 Cells; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054365:Chemokine CXCL5 / Q000097:blood* / Q000494:pharmacology; D016009:Chi-Square Distribution; D002648:Child; D015179:Colorectal Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000556:secondary; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D014408:Biomarkers, Tumor; C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins