Overexpression of chemokine receptor CXCR2 and ligand CXCL7 in liver metastases from colon cancer is correlated to shorter disease‐free and overall survival

Cancer Science

Thibault Desurmont¹  Nicolas Skrypek¹  Alain Duhamel²  Nicolas Jonckheere¹  Guillaume Millet¹  Emmanuelle Leteurtre¹  Pierre Gosset³  Belinda Duchene¹  Nassima Ramdane²  Mohamed Hebbar¹  Isabelle Van Seuningen¹  François-René Pruvot⁴  Guillemette Huet¹ 

[1] Inserm, U837, Team-5 (Mucins, Epithelial Differentiation, and Carcinogenesis), Jean-Pierre Aubert Research Centre, Université Lille, France;Biostatistics Department, EA2694, UDSL, Univ-Lille Nord de France, CHU Lille, Lille, France;Department of Anatomo-Pathology, GHICL, Saint-Vincent de Paul Hospital, Lille, France;Department of Digestive and Transplantation Surgery, Centre Hospitalier Régional Universitaire de Lille, Lille, France

关键词: 5FU‐based chemotherapy;    colorectal cancer;    CXCL7;    CXCR2;    liver metastasis;   

DOI  :  10.1111/cas.12603

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.