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Changes in plasma chemokine C-C motif ligand 2 levels during treatment with eicosapentaenoic acid predict outcome in patients undergoing surgery for colorectal cancer liver metastasis.
- Source :
-
Oncotarget [Oncotarget] 2016 May 10; Vol. 7 (19), pp. 28139-50. - Publication Year :
- 2016
-
Abstract
- The mechanism of the anti-colorectal cancer (CRC) activity of the omega-3 fatty acid eicosapentaenoic acid (EPA) is not understood. We tested the hypothesis that EPA reduces expression of chemokine C-C motif ligand 2 (CCL2), a pro-inflammatory chemokine with known roles in metastasis.We measured CCL2 in clinical samples from a randomized trial of EPA in patients undergoing liver surgery for CRC liver metastasis (LM) and preclinical models. Genome-wide transcriptional profiling of tumors from EPA-treated patients was performed.EPA decreased CCL2 synthesis by CRC cells in a dose-dependent manner. CCL2 was localized to malignant epithelial cells in human CRCLM. EPA did not reduce CCL2 content in human or mouse tumors compare to control. However, EPA treatment was associated with decreased plasma CCL2 levels compared with controls (P=0.04). Reduction in plasma CCL2 following EPA treatment predicted improved disease-free survival (HR 0.32; P=0.003). Lack of 'CCL2 response' was associated with a specific CRCLM gene expression signature.In conclusion, reduction in plasma CCL2 in patients with CRCLM treated with EPA predicts better clinical outcome and a specific tumor gene expression profile. Further work is needed to validate CCL2 as a therapeutic response biomarker for omega-3 fatty acid treatment of CRC patients.<br />Competing Interests: None of the authors have any potential conflicts of interest to disclose.
- Subjects :
- Animals
Biomarkers, Tumor blood
Disease-Free Survival
Female
Humans
Kaplan-Meier Estimate
Male
Mice
Mice, Inbred C57BL
Treatment Outcome
Antineoplastic Agents therapeutic use
Chemokine CCL2 blood
Colorectal Neoplasms drug therapy
Colorectal Neoplasms mortality
Colorectal Neoplasms pathology
Eicosapentaenoic Acid therapeutic use
Liver Neoplasms drug therapy
Liver Neoplasms secondary
Liver Neoplasms surgery
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27058904
- Full Text :
- https://doi.org/10.18632/oncotarget.8579