Urinary Proteomics for Discovery of Gastric Cancer Biomarkers to Enable Precision Clinical Oncology

OMICS. 2023 Aug;27(8):361-371. doi: 10.1089/omi.2023.0077. Epub 2023 Aug 9.

Abstract

For precision in clinical oncology practice, detection of tumor-derived peptides and proteins in urine offers an attractive and noninvasive alternative for diagnostic or screening purposes. In this study, we report comparative quantitative proteomic profiling of urine samples from patients with gastric cancer and healthy controls using tandem mass tags-based multiplexed mass spectrometry approach. We identified 1504 proteins, of which 246 were differentially expressed in gastric cancer cases. Notably, ephrin A1 (EFNA1), pepsinogen A3 (PGA3), sortilin 1 (SORT1), and vitronectin (VTN) were among the upregulated proteins, which are known to play crucial roles in the progression of gastric cancer. We also found other overexpressed proteins, including shisa family member 5 (SHISA5), mucin like 1 (MUCL1), and leukocyte cell derived chemotaxin 2 (LECT2), which had not previously been linked to gastric cancer. Using a novel approach for targeted proteomics, SureQuant, we validated changes in abundance of a subset of proteins discovered in this study. We confirmed the overexpression of vitronectin and sortilin 1 in an independent set of urine samples. Altogether, this study provides molecular candidates for biomarker development in gastric cancer, and the findings also support the promise of urinary proteomics for noninvasive diagnostics and personalized/precision medicine in the oncology clinic.

Keywords: SureQuant; cancer research; gastric cancer; personalized medicine; precision oncology; proteomics; urine biomarkers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers
  • Biomarkers, Tumor* / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Medical Oncology
  • Mucins
  • Proteins
  • Proteomics / methods
  • Stomach Neoplasms* / diagnosis
  • Vitronectin

Substances

  • Biomarkers, Tumor
  • Vitronectin
  • Proteins
  • Biomarkers
  • MUCL1 protein, human
  • Mucins
  • LECT2 protein, human
  • Intercellular Signaling Peptides and Proteins