Noninvasive Detection of Colorectal Carcinomas Using Serum Protein Biomarkers

J Surg Res. 2020 Feb:246:160-169. doi: 10.1016/j.jss.2019.08.004. Epub 2019 Oct 3.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Colectomy
  • Colonoscopy
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Cross-Sectional Studies
  • Early Detection of Cancer / methods*
  • Feasibility Studies
  • Female
  • Humans
  • Lymphatic Metastasis / diagnosis*
  • Lymphatic Metastasis / pathology
  • Male
  • Mass Screening / methods*
  • Mass Spectrometry / methods
  • Middle Aged
  • Neoplasm Staging
  • Pilot Projects
  • Prospective Studies
  • ROC Curve

Substances

  • Biomarkers, Tumor