RRC ID 38443
Author Kawamura M, Toiyama Y, Tanaka K, Saigusa S, Okugawa Y, Hiro J, Uchida K, Mohri Y, Inoue Y, Kusunoki M.
Title CXCL5, a promoter of cell proliferation, migration and invasion, is a novel serum prognostic marker in patients with colorectal cancer.
Journal Eur J Cancer
Abstract PURPOSE: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.
Volume 48(14)
Pages 2244-51
Published 2012-9-1
DOI 10.1016/j.ejca.2011.11.032
PII S0959-8049(11)00995-6
PMID 22197219
MeSH Adolescent Adult Aged Aged, 80 and over Antibodies, Neutralizing / pharmacology Biomarkers, Tumor / blood* Caco-2 Cells Case-Control Studies Cell Movement* / drug effects Cell Proliferation* / drug effects Chemokine CXCL5 / blood* Chemokine CXCL5 / pharmacology Chi-Square Distribution Child Colorectal Neoplasms / blood* Colorectal Neoplasms / mortality Colorectal Neoplasms / pathology Enzyme-Linked Immunosorbent Assay Female HT29 Cells Humans Immunohistochemistry Japan Kaplan-Meier Estimate Liver Neoplasms / secondary Logistic Models Lymphatic Metastasis Male Middle Aged Multivariate Analysis Neoplasm Invasiveness Prognosis Proportional Hazards Models Receptors, Interleukin-8B / antagonists & inhibitors Receptors, Interleukin-8B / metabolism Recombinant Proteins / pharmacology Risk Assessment Risk Factors Time Factors Up-Regulation Young Adult
IF 7.275
Times Cited 65
Human and Animal Cells CACO-2(RCB0988) DLD-1(RCB1957) LoVo(RCB1639)