Published online Aug 14, 2021. doi: 10.3748/wjg.v27.i30.5076
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
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.
There is an ongoing search for molecular biomarkers to facilitate early diagnosis, and to determine the prognosis of CRC patients.
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.
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.
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.
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.
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.