Shamoun L, Landerholm K, Balboa Ramilo A, Andersson RE, Dimberg J, Wågsäter D. Association of gene and protein expression and genetic polymorphism of CC chemokine ligand 4 in colorectal cancer. World J Gastroenterol 2021; 27(30): 5076-5087 [PMID: 34497436 DOI: 10.3748/wjg.v27.i30.5076]
Corresponding Author of This Article
Dick Wågsäter, PhD, Professor, Department of Medical Cell Biology, Uppsala University, Husargatan 3, Uppsala 75237, Sweden. dick.wagsater@mcb.uu.se
Research Domain of This Article
Biochemistry & Molecular Biology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
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/
World J Gastroenterol. Aug 14, 2021; 27(30): 5076-5087 Published online Aug 14, 2021. doi: 10.3748/wjg.v27.i30.5076
Association of gene and protein expression and genetic polymorphism of CC chemokine ligand 4 in colorectal cancer
Levar Shamoun, Kalle Landerholm, Amanda Balboa Ramilo, Roland E Andersson, Jan Dimberg, Dick Wågsäter
Levar Shamoun, Amanda Balboa Ramilo, Dick Wågsäter, Department of Medical Cell Biology, Uppsala University, Uppsala 75123, Sweden
Levar Shamoun, Department of Laboratory Medicine and Pathology, Region Jönköping County, Jönköping 55305, Sweden
Kalle Landerholm, Roland E Andersson, Department of Surgery, Region Jönköping County, Jönköping 55305, Sweden
Kalle Landerholm, Roland E Andersson, Department of Biomedical and Clinical Science, Linköping University, Linköping 58185, Sweden
Jan Dimberg, Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, Jönköping 55111, Sweden
Author contributions: Dimberg J and Wågsäter D designed and coordinated the study; Shamoun L and Balboa-Ramilo A performed the experiments, acquired and analyzed data; Shamoun L, Balboa-Ramilo A, Landerholm K, Andersson RE, Dimberg J, and Wågsäter D interpreted the data; Landerholm K and Andersson RE recruited the patients; Shamoun L, Dimberg J, and Wågsäter D wrote the manuscript; All authors made critical revisions of the manuscript and approved the final version of the article.
Supported byMedical Research Council of Southeast Sweden (FORSS) and Division of Medical Diagnostics (Futurum), Region Jönköping County, Sweden.
Institutional review board statement: The investigation was approved by the Regional Ethical Review Board in Linköping, Linköping, Sweden and informed consent was obtained from each of the participants.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Dick Wågsäter, PhD, Professor, Department of Medical Cell Biology, Uppsala University, Husargatan 3, Uppsala 75237, Sweden. dick.wagsater@mcb.uu.se
Received: March 31, 2021 Peer-review started: March 31, 2021 First decision: May 28, 2021 Revised: June 7, 2021 Accepted: July 13, 2021 Article in press: July 13, 2021 Published online: August 14, 2021 Processing time: 131 Days and 18.7 Hours
ARTICLE HIGHLIGHTS
Research background
Colorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer death. Inflammatory factors expressed in CRC cells or in the tumor microenvironment play an important role in local immune regulation. Among these factors, chemokines like CC chemokine ligand (CCL) 4 play an important role in facilitating recruitment of leukocytes.
Research motivation
There is an ongoing search for molecular biomarkers to facilitate early diagnosis, and to determine the prognosis of CRC patients.
Research objectives
The aim of the present study was to examine expression of CCL4 and its genetic polymorphism rs10491121 in patients with CRC and to evaluate their association to clinicopathological parameters and prognostic impact.
Research methods
Blood, tumor and paired normal tissue from patients with CRC and blood samples from healthy controls were subjected to an analysis of CCL4 protein using Luminex technology. Reverse transcription quantitative PCR was used to investigate the CCL4 gene expression in CRC tissue and paired normal tissue. For studies on the CCL4 rs10491121 polymorphism in CRC patients and healthy controls, TaqMan genotype assays based on polymerase chain reaction were used.
Research results
The CCL4 protein and messenger RNA expression levels were higher in CRC tissue than in normal paired tissue and the level of CCL4 protein in CRC tissue from patients with localized disease was higher than that in CRC tissue from patients with disseminated disease. Low levels of CCL4 protein in CRC tissue were associated with a 30% lower cancer-specific survival rate in patients. The level of CCL4 in plasma was higher in CRC patients than in healthy controls and was positively correlated with the CCL4 protein level in CRC tissue. There was a difference in polymorphism rs10491121 between localized disease and disseminated disease in the right colon, with a dominance of allele A in localized disease.
Research conclusions
The results from this study indicate that CCL4 expression and gene polymorphism are good markers of prognosis. However, the findings need to be reproduced in larger cohorts.
Research perspectives
The chemokine CCL4 deserves further attention as a clinical prognostic biomarker in CRC. Detailed functional analysis is required to reveal the mechanisms underlying the observed associations between different levels of CCL4 in CRC tissue and different stages of disease.
