title: CXCR4, CXCL12 and the relative CXCL12-CXCR4 expression as prognostic factors in colon cancer.
abstract: The CXCL12-CXCR4 axis is proposed to mediate metastasis formation. In this study, we examined CXCL12, CXCR4 and the relative CXCL12-CXCR4 expression as prognostic factors in two cohorts of colon cancer patients. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to study CXCR4, CXCL12 and relative CXCL12-CXCR4 expression in tissue microarrays. Our study included totally 596 patients, 290 in cohort 1 and 306 in cohort 2. For tumour, node, metastasis (TNM) stage III, low nuclear expression of CXCR4 was a positive prognostic factor for 5-year disease-free survival (DFS) in cohort 1 (P = 0.007) and cohort 2 (P = 0.023). In multivariate analysis for stage III, nuclear expression of CXCR4 in cohort 1 was confirmed as a prognostic factor for DFS (hazard ratio (HR), 0.27; 95 % CI, 0.09 to 0.77). For TNM stage III, high cytoplasmic expression of CXCL12 was associated with better 5-year DFS in both cohorts (P = 0.006 and P = 0.006, respectively). We further validated the positive prognostic value of CXCL12 expression for 5-year DFS in stage III with ISH (P = 0.022). For TNM stage III, the relative CXCL12-CXCR4 expression (CXCL12 > CXCR4 vs CXCL12 = CXCR4 vs CXCL12 < CXCR4) was a prognostic factor for 5-year DFS in cohort 1 (92 % vs 46 % vs 31 %, respectively; P < 0.001) and cohort 2 (92 % vs 66 % vs 30 %, respectively; P = 0.006). In conclusion, CXCL12 and relative CXCL12-CXCR4 expression are independent prognostic factors for 5-year DFS in TNM stage III colon cancer.
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Post box 7804, 5020, Bergen, Norway. luka.stanisavljevic@uib.no.
authors.forename: Luka
authors.initials: L
authors.lastname: Stanisavljević
authors.affiliation: Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway.
authors.forename: Jörg
authors.initials: J
authors.lastname: Aßmus
authors.affiliation: Department of Surgery, Haraldsplass Deaconess Hospital, Bergen, Norway.
authors.forename: Kristian Eeg
authors.initials: KE
authors.lastname: Storli
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Sabine Maria
authors.initials: SM
authors.lastname: Leh
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Post box 7804, 5020, Bergen, Norway.|Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Olav
authors.initials: O
authors.lastname: Dahl
authors.affiliation: Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Mette Pernille
authors.initials: MP
authors.lastname: Myklebust
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4
keywords: CXCL12; CXCR4; Colorectal cancer; Immunohistochemistry; In situ hybridization