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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2019; 25(31): 4383-4404
Published online Aug 21, 2019. doi: 10.3748/wjg.v25.i31.4383
Systemic inflammation in colorectal cancer: Underlying factors, effects, and prognostic significance
Anne E Tuomisto, Markus J Mäkinen, Juha P Väyrynen
Anne E Tuomisto, Markus J Mäkinen, Juha P Väyrynen, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu 90220, Finland
Anne E Tuomisto, Markus J Mäkinen, Juha P Väyrynen, Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu 90220, Finland
Juha P Väyrynen, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, United States
Author contributions: All authors equally contributed to the literature review and design, writing, revision and editing of the manuscript.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
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/
Corresponding author: Anne E Tuomisto, PhD, Research Scientist, Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, POB 21, Oulu 90029, Finland. anne.tuomisto@oulu.fi
Telephone: +358-29-4485946 Fax: +358-8-344084
Received: April 25, 2019
Peer-review started: April 25, 2019
First decision: May 24, 2019
Revised: June 7, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: August 21, 2019
Abstract

Systemic inflammation is a marker of poor prognosis preoperatively present in around 20%-40% of colorectal cancer patients. The hallmarks of systemic inflammation include an increased production of proinflammatory cytokines and acute phase proteins that enter the circulation. While the low-level systemic inflammation is often clinically silent, its consequences are many and may ultimately lead to chronic cancer-associated wasting, cachexia. In this review, we discuss the pathogenesis of cancer-related systemic inflammation, explore the role of systemic inflammation in promoting cancer growth, escaping antitumor defense, and shifting metabolic pathways, and how these changes are related to less favorable outcome.

Keywords: Colorectal cancer, Inflammation, Prognosis, Cytokine, Chemokine, C-reactive protein, Glasgow prognostic score, Cachexia, Metastasis

Core tip: Increasing evidence indicates that systemic inflammation has wide-ranging effects on colorectal cancer (CRC) pathogenesis, spanning from supporting primary tumor growth by promoting tumor cell proliferation to helping angiogenesis by enhancing the availability of pro-angiogenic molecules, to suppressing anti-tumor immunity by recruiting anti-inflammatory cell types, and to shaping pre-metastatic niches to promote subsequent metastasis. Systemic inflammatory biomarkers, such as circulating acute phase proteins, cytokines, exosomes, and leukocytes, may help to classify CRC patients into useful prognostic categories. However, further larger-scale studies are needed to determine optimal marker combinations for selecting patients to receive specific treatments.