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J Surg Res. 2019 Oct 3;246:160-169. doi: 10.1016/j.jss.2019.08.004. [Epub ahead of print]

Noninvasive Detection of Colorectal Carcinomas Using Serum Protein Biomarkers.

Author information

1
University of Wisconsin-Madison Biotechnology Center, Madison, Wisconsin; Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Department of Biochemistry, University of Wisconsin, Madison, Wisconsin.
2
Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin, Madison, Wisconsin; Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
3
Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin.
4
Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin, Madison, Wisconsin.
5
Department of Radiology, University of Wisconsin, UW Medical Foundation Madison, Wisconsin.
6
University of Wisconsin-Madison Biotechnology Center, Madison, Wisconsin; Department of Biochemistry, University of Wisconsin, Madison, Wisconsin.
7
Department of Surgery, University of Alabama-Birmingham, Birmingham, Alabama. Electronic address: gkennedy@uabmc.edu.

Abstract

BACKGROUND:

A major roadblock to reducing the mortality of colorectal cancer (CRC) is prompt detection and treatment, and a simple blood test is likely to have higher compliance than all of the current methods. The purpose of this report is to examine the utility of a mass spectrometry-based blood serum protein biomarker test for detection of CRC.

MATERIALS AND METHODS:

Blood was drawn from individuals (n = 213) before colonoscopy or from patients with nonmetastatic CRC (n = 50) before surgery. Proteins were isolated from the serum of patients using targeted liquid chromatography-tandem mass spectrometry. We designed a machine-learning statistical model to assess these proteins.

RESULTS:

When considered individually, over 70% of the selected biomarkers showed significance by Mann-Whitney testing for distinguishing cancer-bearing cases from cancer-free cases. Using machine-learning methods, peptides derived from epidermal growth factor receptor and leucine-rich alpha-2-glycoprotein 1 were consistently identified as highly predictive for detecting CRC from cancer-free cases. A five-marker panel consisting of leucine-rich alpha-2-glycoprotein 1, epidermal growth factor receptor, inter-alpha-trypsin inhibitor heavy-chain family member 4, hemopexin, and superoxide dismutase 3 performed the best with 70% specificity at over 89% sensitivity (area under the curve = 0.86) in the validation set. For distinguishing regional from localized cancers, cross-validation within the training set showed that a panel of four proteins consisting of CD44 molecule, GC-vitamin D-binding protein, C-reactive protein, and inter-alpha-trypsin inhibitor heavy-chain family member 3 yielded the highest performance (area under the curve = 0.75).

CONCLUSIONS:

The minimally invasive blood biomarker panels identified here could serve as screening/detection alternatives for CRC in a human population and potentially useful for staging of existing cancer.

KEYWORDS:

Biomarkers; Colorectal neoplasms; Proteomic

PMID:
31586890
DOI:
10.1016/j.jss.2019.08.004

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