Serum immunoinflammation-related protein complexes discriminate between inflammatory bowel disease and colorectal cancer

  • Y. H. Sun
  • J. Li
  • H. J. Shu
  • Z. L. LiEmail author
  • J. M. QianEmail author
Research Article



Inflammatory bowel disease (IBD) is an important risk factor for colon cancer. Novel serum immunoinflammation-related protein complexes (IIRPCs) have shown associations with early cancer detection. Herein, we investigated the potential of serum IIRPCs for discriminating between IBD and colorectal cancer (CRC) patients.


Serum protein complexes of 65 healthy controls, 57 CRC, 69 (ulcerative colitis) UC, and 67 (Crohn's disease) CD patients were isolated by native-PAGE. The gray values of serum IIRPCs bands in the gel were quantified using Quantity One software. The receiver-operating characteristic (ROC) curves were constructed to assess the discriminating ability by calculating the area under the ROC curve.


The serum IIRPCs levels in IBD and CRC patients were significantly elevated compared to healthy controls. ROC analysis indicated certain diagnostic ability of serum IIRPCs in differentiating IBD from CRC. Specifically, “a3” complex discriminated UC from CRC, with an AUC value of 0.722, sensitivity of 69.4% and specificity of 63.8%. Similarly, “b4” complex discriminated UC from CRC, with an AUC value of 0.709, sensitivity of 70.4%, and specificity of 60.0%. In addition, the “a3” complex also discriminated CD from CRC, with an AUC value of 0.785, sensitivity of 73.1%, and specificity of 74.1%, while the “b4” complex showed a tendency to discriminate CD from CRC, with an AUC value of 0.663, sensitivity of 67.9% and specificity of 50.0%. Thus, an equation based on multiple IIRPCs was built to further improve the discriminating power.


Serum IIRPCs can be used to discriminate IBD from CRC and may also be associated with early screening of colitis-associated cancer.


Immunoinflammation-related protein complexes Inflammatory bowel disease Colorectal cancer Diagnosis 



The authors thank to the staff in IBD clinic in Peking Union Medical College Hospital for assistance with research sample coordination; and all patients and healthy individuals who participated in this study.


This work was supported by a Health Research & Special Projects Grant of China (no. 201002020).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

This study was approved by the ethic committee of Peking Union Medical College Hospital (PUMCH, approval number S-K462) and all serum were remains from clinical laboratory.

Informed consent

Written informed consent was obtained from all participants.


  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.CrossRefGoogle Scholar
  2. 2.
    Chiba T, Marusawa H, Ushijima T. Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation. Gastroenterology. 2012;143:550–63.CrossRefGoogle Scholar
  3. 3.
    Lucas C, Barnich N, Nguyen H. Microbiota, inflammation and colorectal cancer. Int J Mol Sci. 2017;18:1310.CrossRefGoogle Scholar
  4. 4.
    Wang Y, Song G, Wang Y, Qiu L, Qin X, Liu H, et al. Elevated serum levels of circulating immunoinflammation-related protein complexes are associated with cancer. J Proteome Res. 2014;13:710–9.CrossRefGoogle Scholar
  5. 5.
    Hovde Ø, Høivik ML, Henriksen M, Solberg IC, Småstuen MC, Moum BA. Malignancies in patients with inflammatory bowel disease: results from 20 years of follow-up in the IBSEN study. J Crohn’s Colit. 2017;11:571–7.Google Scholar
  6. 6.
    Nikolaus S, Schreiber S. Diagnostics of inflammatory bowel disease. Gastroenterology. 2007;133:1670–89.CrossRefGoogle Scholar
  7. 7.
    Jain U, Otley AR, Van Limbergen J, Stadnyk AW. The complement system in inflammatory bowel disease. Inflamm Bowel Dis. 2014;20:1628–37.CrossRefGoogle Scholar
  8. 8.
    Laufer J, Oren R, Goldberg I, Horwitz A, Kopolovic J, Chowers Y, et al. Cellular localization of complement C3 and C4 transcripts in intestinal specimens from patients with Crohn’s disease. Clin Exp Immunol. 2000;120:30–7.CrossRefGoogle Scholar
  9. 9.
    Sugihara T, Kobori A, Imaeda H, Tsujikawa T, Amagase K, Takeuchi K, et al. The increased mucosal mRNA expressions of complement C3 and interleukin-17 in inflammatory bowel disease. Clin Exp Immunol. 2010;160:386–93.CrossRefGoogle Scholar
  10. 10.
    Preisker S, Brethack AK, Bokemeyer A, Bettenworth D, Sina C, Derer S. Crohn’s disease patients in remission display an enhanced intestinal IgM+ B cell count in concert with a strong activation of the intestinal complement system. Cells. 2019;8(1):78.CrossRefGoogle Scholar
  11. 11.
    Sina C, Kemper C, Derer S. The intestinal complement system in inflammatory bowel disease: shaping intestinal barrier function. Semin Immunol. 2018;37:66–73.CrossRefGoogle Scholar
  12. 12.
    Vucelić B, Milicić D, Krznarić Z, Korać B, Sentić M, Hadzić N, et al. Serum acute phase proteins for determining disease activity of ulcerative colitis and Crohn disease. Acta Med Aust. 1991;18:100–5.Google Scholar
  13. 13.
    Vanuytsel T, Vermeire S, Cleynen I. The role of Haptoglobin and its related protein, Zonulin, in inflammatory bowel disease. Tissue Barr. 2013;1(5):e27321.CrossRefGoogle Scholar
  14. 14.
    Wang YN, Li J, Zheng WY, Wu D, Yang H, Li Y, et al. Clinical characteristics of ulcerative colitis-related colorectal cancer in Chinese patients. J Digest Dis. 2017;18:684–90.CrossRefGoogle Scholar
  15. 15.
    Šimurina M, de Haan N, Vučković F, Kennedy NA, Štambuk J, Falck D, et al. Glycosylation of immunoglobulin G associates with clinical features of inflammatory bowel diseases. Gastroenterology. Am Gastroenterol Assoc. 2018;154:1320–33.CrossRefGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  1. 1.Department of Gastroenterology, Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingPeople’s Republic of China
  2. 2.Department of Biophysics and Structural Biology, Institute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical CollegeBeijingPeople’s Republic of China

Personalised recommendations