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. 2018 Jun 11:2018:7436205.
doi: 10.1155/2018/7436205. eCollection 2018.

Immune Condition of Colorectal Cancer Patients Featured by Serum Chemokines and Gene Expressions of CD4+ Cells in Blood

Takuya Komura  1 , Masaaki Yano  2 , Akimitsu Miyake  3 , Hisashi Takabatake  2 , Masaki Miyazawa  2 , Norihiko Ogawa  1 , Akihiro Seki  1 , Masao Honda  4 , Takashi Wada  5 , Shigeyuki Matsui  3 , Shuichi Kaneko  1   4 , Yoshio Sakai  4
Affiliations

Immune Condition of Colorectal Cancer Patients Featured by Serum Chemokines and Gene Expressions of CD4+ Cells in Blood

Takuya Komura et al. Can J Gastroenterol Hepatol. .

Abstract

Background: Colorectal cancer (CRC), the most common malignancy worldwide, causes inflammation. We explored the inflammatory pathophysiology of CRC by assessing the peripheral blood parameters.

Methods: The differences in gene expression profiles of whole blood cells and cell subpopulations between CRC patients and healthy controls were analyzed using DNA microarray. Serum cytokine/chemokine concentrations in CRC patients and healthy controls were measured via multiplex detection immunoassays. In addition, we explored correlations between the expression levels of certain genes of peripheral CD4+ cells and serum chemokine concentrations.

Results: The gene expression profiles of peripheral CD4+ cells of CRC patients differed from those of healthy controls, but this was not true of CD8+ cells, CD14+ cells, CD15+ cells, or CD19+ cells. Serum IL-8 and eotaxin-1 levels were significantly elevated in CRC patients, and the levels substantially correlated with the expression levels of certain genes of CD4+ cells. Interestingly, the relationships between gene expression levels in peripheral CD4+ cells and serum IL-8 and eotaxin-1 levels resembled those of monocytes/macrophages, not T cells.

Conclusions: Serum IL-8 and eotaxin-1 concentrations increased and were associated with changes in the gene expression of peripheral CD4+ cells in CRC patients.

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Figures

Figure 1
Figure 1
Serum concentrations of eotaxin-1 and IL-8. Sera were obtained from CRC patients (n=30) prior to treatment and healthy volunteers (n=28). The serum concentrations of cytokines and chemokines were measured using a multiplex bead immunoassay system. (a) IL-8 levels; (b) eotaxin-1 levels. IL-8 levels in CRC patients by clinical stage (c) and eotaxin-1 levels by clinical stage (d). Correlations between IL-8 and CEA levels in CRC patients (e) and between IL-8 and CA19-9 levels (f).
Figure 2
Figure 2
Unsupervised clustering analysis of the gene expression profiles of subfractionated peripheral blood cells. The dendrogram used for clustering using employed both correlations and average linkage for unsupervised analysis of the gene expression profile of peripheral blood. Significant up- or downregulated changes in gene expression (≥1.5-fold) in whole blood and CD4+ cells of CRC patients (compared to healthy volunteers) were observed for 3,243 and 2,459 genes at P-values <0.05, respectively, but few such changes were observed in CD8+ cells, CD14+ cells, or CD15+ cells (1,475, 128, and 333 genes; P <0.05, respectively).
Figure 3
Figure 3
Spearman correlation coefficients between genes expressed by CD4+ cells. Genes expressed by CD4+ cells of CRC patients and healthy volunteers, with two-sided p-values, (a) eotaxin-1 and (b) IL-8 levels.
See this image and copyright information in PMC

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