Plasma cytokine levels and the presence of colorectal cancer

PLoS One. 2019 Mar 18;14(3):e0213602. doi: 10.1371/journal.pone.0213602. eCollection 2019.


Background/aims: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood*
  • Case-Control Studies
  • Colorectal Neoplasms / blood*
  • Cytokines / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / blood*


  • Biomarkers, Tumor
  • Cytokines
  • Neoplasm Proteins

Grants and funding

This work was supported in part by a Fukushima grant for development of medical and welfare devices, and development of low-cost, rapid, and noninvasive diagnostic technology for cancer using salivary biomarkers, Japan; and grant no. 16H03166 from the Japan Society for the Promotion of Science, for visualization of cancer by cytokine coding methods and biosensor-arrays with micro-capsules (P.I. M. Yamaguchi).