Open AccessOverexpression of chemokine receptor CXCR 2 and ligand CXCL 7 in liver metastases from colon cancer is correlated to shorter disease‐free and overall survival
Author(s) -
Desurmont Thibault,
Skrypek Nicolas,
Duhamel Alain,
Jonckheere Nicolas,
Millet Guillaume,
Leteurtre Emmanuelle,
Gosset Pierre,
Duchene Belinda,
Ramdane Nassima,
Hebbar Mohamed,
Van Seuningen Isabelle,
Pruvot FrançoisRené,
Huet Guillemette,
Truant Stéphanie
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12603
Subject(s) - metastasis , colorectal cancer , medicine , chemotherapy , chemokine , chemokine receptor , cancer , immunology , receptor , cancer research , oncology
Our aim was to analyze the potential role of chemokine receptors CXCR 2 and CXCR 4 signalling pathways in liver metastatic colorectal cancer ( CRC ) relapse. CXCR 2, CXCR 4, 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 CXCR 2 immunohistochemical staining were carried out using CRC liver metastasis samples. Expression levels of CXCR 2, CXCR 4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients’ outcome. CXCR 2 and CXCL 7 overexpression are correlated to shorter overall and disease‐free survival. By multivariate analysis, CXCR 2 and CXCL 7 expressions are independent factors of overall and disease‐free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR 2: treated group 1.89 (0.02–50.92) vs 0.55 (0.07–3.22), P = 0.016. CXCL 7 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 CXCL 7/ CXCR 2 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 CXCR 2/ CXCL 7 signalling pathways could provide new potential therapeutic opportunities.