Article | Published:

Molecular Diagnostics

Fibroblast growth factor 21 as a circulating biomarker at various stages of colorectal carcinogenesis

British Journal of Cancervolume 119pages13741382 (2018) | Download Citation

Abstract

Background

Despite evidence that inflammation and metabolism play a crucial role in colorectal carcinogenesis, there have been few studies on the association of inflammatory and metabolic protein biomarkers in various stages of colorectal carcinogenesis.

Methods

Ninety-two inflammatory and metabolic biomarkers were measured in plasma samples of participants of screening colonoscopy. Markers identified to be significantly associated with the presence of advanced colorectal neoplasia (ACN) in a discovery set (n = 204) were validated in an independent replication set (n = 422). Adjusted associations with the presence of non-advanced adenomas (NAA), advanced precancerous lesions (APL) and colorectal cancer (CRC) were quantified by multiple logistic regression.

Results

Out of the 92 inflammatory proteins, 72 markers were evaluable and 8 showed statistically significant associations with the odds of ACN after full adjustment for potential risk factors for CRC in the discovery set. One of these, fibroblast growth factor 21 (FGF-21), could be validated in the replication set. The multivariable-adjusted odds ratio (OR) reached 2.65 (95% CI, 1.50–4.81) for individuals with FGF-21 levels within the highest tertile, compared to those within the lowest tertile (Ptrend across tertiles = 0.001). Separate models revealed fully adjusted ORs for NAA, APL and CRC of 2.99 (95% CI, 1.45–6.58, Ptrend = 0.005), 2.24 (95% CI, 1.18–4.44, Ptrend = 0.021) and 3.92 (95% CI, 1.51–12.18, Ptrend = 0.003), respectively.

Conclusions

Circulating FGF-21 level is associated with increased risk of early and late stages of colorectal carcinogenesis, supporting a role of inflammation and metabolism at all stages of colorectal carcinogenesis, and suggesting potential use of this biomarker for risk stratification in CRC screening.

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Data availability

The data sets used and analysed during the current study are available from the corresponding author.

Additional information

Note: This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

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Acknowledgements

The authors acknowledge the cooperation of gastroenterology practices and clinics in patient recruitment and of Labor Limbach in sample collection. They also thank Dr. Katarina Cuk, Dr. Katja Butterbach, Ulrike Schlesselmann, Sabine Eichenherr and Romana Kimmel for their excellent work in laboratory preparation of blood samples and Isabel Lerch, Susanne Kohler, Utz Benscheid, Jason Hochhaus and Maria Kuschel for their contribution in data collection, monitoring and documentation. Additionally, they are grateful to Dr. Simone Werner for her effort in project management. The BliTz study was partly funded by grants from the German Research Council (DFG, grant no. BR1704/16-1). The ASTER study was funded by the German Cancer Consortium (DKTK). The work of J.Q. was partly supported by the China Scholarship Council (CSC). The work of Yesilda Balavarca was partly supported by a grant from the German Cancer Aid (Deutsche Krebshilfe #111365).

Author information

Affiliations

  1. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

    • Jing Qian
    • , Kaja Tikk
    • , Korbinian Weigl
    •  & Hermann Brenner
  2. Medical Faculty Heidelberg, University of Heidelberg, 69120, Heidelberg, Germany

    • Jing Qian
    • , Korbinian Weigl
    •  & Hermann Brenner
  3. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

    • Kaja Tikk
    • , Korbinian Weigl
    •  & Hermann Brenner
  4. Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120, Heidelberg, Germany

    • Yesilda Balavarca
    •  & Hermann Brenner

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Contributions

H.B. conceived the project and supervised the study. J.Q. analysed and interpreted the data and wrote the manuscript. K.T. and K.W. coordinated the study and provided clinical samples. Y.B. provided statistical support. All authors read, revised the manuscript and approved the final version.

Ethics approval and consent to participate

All the studies involved were approved by the Ethics Committee of the University of Heidelberg (Heidelberg, Germany) and by the Ethics Committee of each participating centre. Written informed consent was obtained from all participants.

Competing interests

The authors declare no competing interests.

Note:

This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0)

Corresponding author

Correspondence to Hermann Brenner.

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DOI

https://doi.org/10.1038/s41416-018-0280-x