Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun;126(10):1387-1393.
doi: 10.1038/s41416-022-01712-x. Epub 2022 Jan 28.

Early detection of colorectal neoplasia: application of a blood-based serological protein test on subjects undergoing population-based screening

Jakob Kleif  1   2   3 , Lars Nannestad Jørgensen  4   5 , Jakob W Hendel  6 , Mogens R Madsen  7 , Jesper Vilandt  8 , Søren Brandsborg  9 , Lars Maagaard Andersen  10 , Ali Khalid  11 , Peter Ingeholm  12 , Linnea Ferm  13 , Gerard J Davis  14 , Susan H Gawel  14 , Frans Martens  15 , Berit Andersen  10   16 , Morten Rasmussen  5 , Ib Jarle Christensen  13 , Hans Jørgen Nielsen  13   4
Affiliations

Early detection of colorectal neoplasia: application of a blood-based serological protein test on subjects undergoing population-based screening

Jakob Kleif et al. Br J Cancer. 2022 Jun.

Abstract

Background: Blood-based biomarkers used for colorectal cancer screening need to be developed and validated in appropriate screening populations. We aimed to develop a cancer-associated protein biomarker test for the detection of colorectal cancer in a screening population.

Methods: Participants from the Danish Colorectal Cancer Screening Program were recruited. Blood samples were collected prior to colonoscopy. The cohort was divided into training and validation sets. We present the results of model development using the training set. Age, sex, and the serological proteins CEA, hsCRP, TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, ferritin and B2M were used to develop a signature test to discriminate between participants with colorectal cancer versus all other findings at colonoscopy.

Results: The training set included 4048 FIT-positive participants of whom 242 had a colorectal cancer. The final model for discriminating colorectal cancer versus all other findings at colonoscopy had an AUC of 0.70 (95% CI: 0.66-0.74) and included age, sex, CEA, hsCRP, HE4 and ferritin.

Conclusion: The performance of the biomarker signature in this FIT-positive screening population did not reflect the positive performance of biomarker signatures seen in symptomatic populations. Additional biomarkers are needed if the serological biomarkers are to be used as a frontline screening test.

PubMed Disclaimer

Conflict of interest statement

SG and GJD are employees of Abbott Laboratories Inc. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow of the study.
Fig. 2
Fig. 2. Receiver-operating characteristic curves for multivariable models.
The receiver-operating characteristic curves for the multivariable models discriminating colorectal cancer (CRC) from all other findings at colonoscopy (remaining); colorectal cancer, high-risk adenomas, and medium-risk adenomas (CRC + HRA + MRA) versus all other findings at colonoscopy (remaining); and colorectal cancer (CRC) versus clean colon (clean) at colonoscopy. formula image CRC vs remaining formula image CRC + HRA + MRA vs remaining. formula image CRC vs clean formula image Flip a coin.
See this image and copyright information in PMC

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66:683–91. doi: 10.1136/gutjnl-2015-310912. - DOI - PubMed
    1. Gawel SH, Lucht M, Gomer H, Treado P, Christensen IJ, Nielsen HJ, et al. Evaluation of algorithm development approaches: Development of biomarker panels for early detection of colorectal lesions. Clin Chim Acta. 2019;498:108–15. doi: 10.1016/j.cca.2019.08.007. - DOI - PubMed
    1. Bailey CE, Hu CY, You YN, Bednarski BK, Rodriguez-Bigas MA, Skibber JM, et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg. 2015;150:17–22. doi: 10.1001/jamasurg.2014.1756. - DOI - PMC - PubMed
    1. Young JP, Win AK, Rosty C, Flight I, Roder D, Young GP, et al. Rising incidence of early-onset colorectal cancer in Australia over two decades: report and review. J Gastroenterol Hepatol. 2015;30:6–13. doi: 10.1111/jgh.12792. - DOI - PubMed

Publication types