Research Article: Plasma cytokine levels and the presence of colorectal cancer

Date Published: March 18, 2019

Publisher: Public Library of Science

Author(s): Masaki Yamaguchi, Shin Okamura, Taiki Yamaji, Motoki Iwasaki, Shoichiro Tsugane, Vivek Shetty, Tomonobu Koizumi, Paul Proost.


Cancer-related activation of cytokine networks are central aspects of tumor development. The goal of the study was to examine the possibility of plasma cytokines for the screening of colorectal cancer (CRC).

We carried out a multicenter, hospital-based case-control study in 66 adult Japanese patients with CRC and 87 healthy adult Japanese. A multiplex bead array immunoassay was used to examine 27 different plasma cytokines. Their association with the presence of CRC was evaluated by logistic regression analysis after adjusting for potential confounding factors.

Thirteen plasma cytokines were notably associated with the presence of CRC (p< 0.05). Receiver operating characteristic analysis revealed that the combinatorial assessment of some of these plasma cytokines showed “good” capability for discriminating between CRC patients and control subjects (area under the curve (AUC): 0.819 for the combination of IL-9, Eotaxin, G-CSF, and TNF-α; 0.832 for the combination of IL-4, IL-8, Eotaxin, IP-10, and TNF-α). Individual cytokine assessments presented lower AUCs (0.657–0.755) than the combinatorial cytokine assessments. The levels of several plasma cytokines varied significantly between CRC patients and control subjects, suggesting the possibility of differentially expressed plasma cytokines as potential biomarkers for detecting the presence of CRC. Our results should be validated in other populations.

Partial Text

Colorectal cancer (CRC) is the second most common cancer occurring in females and the third most common cancer in males worldwide [1]. The disease affects 1.36 million people globally, accounting for nearly 10% of cancers [2]. CRC incidence and mortality continue to increase, owing mainly to population aging, and possibly to factors including a “westernized” diet, lifestyle, and lack of health-care infrastructure and resources.

The study results supported our working hypothesis that the levels of some plasma cytokines vary depending on the presence of CRC. Even after controlling for gender, age, and hospital, the plasma levels of CRC patients and controls differed significantly in terms of the following 13 cytokines: IL-4, IL-8, IL-9, IL-17A, Eotaxin, G-CSF, IFN-γ, TNF-α, IP-10, MIP-1α, MIP-1β, PDGF-BB, and RANTES (Table 2 and Fig 1, p < 0.05). The combinatorial assessment of some of these plasma cytokines showed promise for detecting the presence of CRC. In fact, the ROC analysis showed that the IL-9 and IL-4 models had “good” capability for discriminating between CRC patients and controls (Table 4 and Fig 2). These two models showed similar AUC values, although some differences were observed; the performance of the IL-9 model was excellent with respect to specificity, while the IL-4 model balanced both sensitivity and specificity (Table 5).   Source:


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