Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2017; 23(34): 6212-6219
Published online Sep 14, 2017. doi: 10.3748/wjg.v23.i34.6212
Circulating inflammatory factors associated with worse long-term prognosis in colorectal cancer
Renate S Olsen, Johnny Nijm, Roland E Andersson, Jan Dimberg, Dick Wågsäter
Renate S Olsen, Division of Medical Diagnostics, Department of Laboratory Medicine, Region Jönköping County, SE-44185 Jönköping, Sweden
Renate S Olsen, Dick Wågsäter, Division of Drug Research, Department of Medicine and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University, SE-58185 Linköping, Sweden
Johnny Nijm, Division of Medical Diagnostics, Department of Clinical Physiology, Region Jönköping County, SE-44185 Jönköping, Sweden
Roland E Andersson, Department of Surgery, Region Jönköping County, SE-44185 Jönköping, Sweden
Roland E Andersson, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, SE-58185 Linköping, Sweden
Jan Dimberg, Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, SE-55111 Jönköping, Sweden
Author contributions: All authors contributed to conception and design of the research, acquisition of data or analysis and interpretation of data; drafted the article and approved the version of the article to be published.
Supported by The Foundation of Clinical Cancer Research, Jönköping, No. 151124-6; and FORSS, the Research Council of Southeastern Sweden, No. FORSS-373251.
Institutional review board statement: The study was approved by the Regional Ethical Review Board in Linköping, Linköping, Sweden.
Informed consent statement: Written informed consent was obtained from each patient.
Conflict-of-interest statement: The authors have no conflict of interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Dick Wågsäter, Professor, Division of Drug Research, Department of Medicine and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University, SE-58185 Linköping, Sweden. dick.wagsater@liu.se
Telephone: +46-10-1032058 Fax: +46-13-149403
Received: February 3, 2017
Peer-review started: February 9, 2017
First decision: April 21, 2017
Revised: May 12, 2017
Accepted: July 12, 2017
Article in press: July 12, 2017
Published online: September 14, 2017
Abstract
AIM

To investigate association of circulating inflammatory factors at the time of colorectal cancer (CRC) surgery with survival.

METHODS

Plasma levels from 174 CRC patients (69 females and 105 men), with median age 70 years (range 29-90), localized in the colon (n = 105) or rectum (n = 69), with stage I (n = 24), stage II (n = 54), stage III (n = 67) and stage IV (n = 29) were measured using commercially available Bio-Plex Pro™ Human Chemokine Panel 40-Plex, including 40 different chemokines, cytokines and interleukins. The prognostic association of each inflammatory factor was analysed as CRC-specific and total mortality.

RESULTS

Out of 174 patients, 66 died during the follow-up, 40 because of CRC specific mortality. High tertile levels of 8 factors were significantly associated with increased CRC-specific mortality, of which CCL1, CCL20, CCL24, CX3CL1, IL-4 and TNF-α remained significant in a multivariate Cox regression analysis. High tertile levels of 14 factors were associated with increased total mortality, of which CCL1, CCL15, CCL20, CX3CL1, CXCL13, IFN-γ, IL-2, IL-4 and IL-10 remained significant after adjustment for clinical covariates. For most of the inflammatory factors the association between higher tertile levels and an increased mortality in general appeared two years after surgery. High tertile levels of TNF-α and CCL24 were exclusively associated with CRC-specific mortality. The distribution of these factors were not associated with TNM stage with exception for CCL20.

CONCLUSION

High plasma levels of inflammatory factors are associated with increased risk of mortality among CRC patients and could be potential biomarkers for revealing prognosis.

Keywords: Colorectal cancer, Inflammation, Cytokines, Plasma, Prognosis, Mortality

Core tip: Plasma levels of 40 different cytokines, chemokines and interleukins were analyzed in colorectal cancer (CRC) patients of which high tertile levels of nine factors were associated with total mortality and six factors with CRC-specific mortality. For most of the inflammatory factors the association between higher tertile levels and an increased mortality in general appeared two years after surgery.