Screening of novel serum biomarkers for gastric cancer in coastal populations using a protein microarray

Cancer Sci. 2023 Aug;114(8):3396-3410. doi: 10.1111/cas.15876. Epub 2023 Jun 8.

Abstract

Gastric cancer (GC) has high rates of morbidity and mortality, and this phenomenon is particularly evident in coastal regions where local dietary habits favor the consumption of pickled foods such as salted fish and vegetables. In addition, the diagnosis rate of GC remains low due to the lack of diagnostic serum biomarkers. Therefore, in this study, we aimed to identify potential serum GC biomarkers for use in clinical practice. To identify candidate biomarkers of GC, 88 serum samples were first screened using a high-throughput protein microarray to measure the levels of 640 proteins. Then, 333 samples were used to validate the potential biomarkers using a custom antibody chip. ELISA, western blot, and immunohistochemistry were then used to verify the expression of the target proteins. Finally, logistic regression was performed to select serum proteins for the diagnostic model. As a result, five specific differentially expressed proteins, TGFβ RIII, LAG-3, carboxypeptidase A2, Decorin and ANGPTL3, were found to have the ability to distinguish GC. Logistic regression analysis showed that the combination of carboxypeptidase A2 and TGFβ RIII had superior potential for diagnosing GC (area under the ROC curve [AUC] = 0.801). The results suggested that these five proteins alone and the combination of carboxypeptidase A2 and TGFβ RIII may be used as serum markers for the diagnosis of GC.

Keywords: biomarkers; gastric cancer; protein microarray; proteomics; serum.

MeSH terms

  • Angiopoietin-Like Protein 3
  • Biomarkers, Tumor*
  • Carboxypeptidases A
  • Early Detection of Cancer
  • Humans
  • Protein Array Analysis
  • ROC Curve
  • Stomach Neoplasms* / diagnosis

Substances

  • Biomarkers, Tumor
  • Carboxypeptidases A
  • ANGPTL3 protein, human
  • Angiopoietin-Like Protein 3