title: Overexpression of chemokine receptor CXCR2 and ligand CXCL7 in liver metastases from colon cancer is correlated to shorter disease-free and overall survival.
abstract: Our aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2, CXCR4, and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease-free survival of patients having received, or not received, a neoadjuvant chemotherapy regimen. Quantitative RT-PCR and CXCR2 immunohistochemical staining were carried out using CRC liver metastasis samples. Expression levels of CXCR2, CXCR4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients' outcome. CXCR2 and CXCL7 overexpression are correlated to shorter overall and disease-free survival. By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease-free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR2: treated group 1.89 (0.02-50.92) vs 0.55 (0.07-3.22), P = 0.016. CXCL7 was overexpressed close to significance, 0.40 (0.00-7.85) vs 0.15 (0.01-7.88), P = 0.12. We show the involvement of CXCL7/CXCR2 signalling pathways as a predictive factor of poor outcome in metastatic CRC. 5-Fluorouracil-based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug-resistant tumors. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities.
authors.affiliation: Inserm, U837, Team-5 (Mucins, Epithelial Differentiation, and Carcinogenesis), Jean-Pierre Aubert Research Centre, Université Lille, France; Department of Digestive and Visceral Surgery, GHICL, Saint-Vincent de Paul Hospital, Lille, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Desurmont
authors.forename: Nicolas
authors.initials: N
authors.lastname: Skrypek
authors.forename: Alain
authors.initials: A
authors.lastname: Duhamel
authors.forename: Nicolas
authors.initials: N
authors.lastname: Jonckheere
authors.forename: Guillaume
authors.initials: G
authors.lastname: Millet
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leteurtre
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.forename: Belinda
authors.initials: B
authors.lastname: Duchene
authors.forename: Nassima
authors.initials: N
authors.lastname: Ramdane
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hebbar
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van Seuningen
authors.forename: François-René
authors.initials: FR
authors.lastname: Pruvot
authors.forename: Guillemette
authors.initials: G
authors.lastname: Huet
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Truant
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000069287:Capecitabine; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015398:Signal Transduction / Q000235:genetics; D001620:beta-Thromboglobulin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: C527276:CXCR4 protein, human; D009944:Organoplatinum Compounds; C061615:PPBP protein, human; D019718:Receptors, CXCR4; D023063:Receptors, Interleukin-8B; D001620:beta-Thromboglobulin; D003841:Deoxycytidine; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: 5FU-based chemotherapy; CXCL7; CXCR2; colorectal cancer; liver metastasis