A Serological Biopsy Using Five Stomach-Specific Circulating Biomarkers for Gastric Cancer Risk Assessment: A Multi-Phase Study

Am J Gastroenterol. 2017 May;112(5):704-715. doi: 10.1038/ajg.2017.55. Epub 2017 Mar 21.

Abstract

Objectives: We aimed to assess a serological biopsy using five stomach-specific circulating biomarkers-pepsinogen I (PGI), PGII, PGI/II ratio, anti-Helicobacter pylori (H. pylori) antibody, and gastrin-17 (G-17)-for identifying high-risk individuals and predicting risk of developing gastric cancer (GC).

Methods: Among 12,112 participants with prospective follow-up from an ongoing population-based screening program using both serology and gastroscopy in China, we conducted a multi-phase study involving a cross-sectional analysis, a follow-up analysis, and an integrative risk prediction modeling analysis.

Results: In the cross-sectional analysis, the five biomarkers (especially PGII, the PGI/II ratio, and H. pylori sero-positivity) were associated with the presence of precancerous gastric lesions or GC at enrollment. In the follow-up analysis, low PGI levels and PGI/II ratios were associated with higher risk of developing GC, and both low (<0.5 pmol/l) and high (>4.7 pmol/l) G-17 levels were associated with higher risk of developing GC, suggesting a J-shaped association. In the risk prediction modeling analysis, the five biomarkers combined yielded a C statistic of 0.803 (95% confidence interval (CI)=0.789-0.816) and improved prediction beyond traditional risk factors (C statistic from 0.580 to 0.811, P<0.001) for identifying precancerous lesions at enrollment, and higher serological biopsy scores based on the five biomarkers at enrollment were associated with higher risk of developing GC during follow-up (P for trend <0.001).

Conclusions: A serological biopsy composed of the five stomach-specific circulating biomarkers could be used to identify high-risk individuals for further diagnostic gastroscopy, and to stratify individuals' risk of developing GC and thus to guide targeted screening and precision prevention.

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Antibodies, Bacterial / blood*
  • Biomarkers / blood
  • Biopsy
  • Cross-Sectional Studies
  • Female
  • Follow-Up Studies
  • Gastric Mucosa / pathology
  • Gastrins / blood*
  • Gastroscopy
  • Helicobacter pylori / immunology*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Pepsinogen A / blood*
  • Pepsinogen C / blood*
  • Precancerous Conditions / blood*
  • Precancerous Conditions / pathology
  • Proportional Hazards Models
  • ROC Curve
  • Risk Assessment / methods
  • Stomach Neoplasms / blood*
  • Stomach Neoplasms / pathology

Substances

  • Antibodies, Bacterial
  • Biomarkers
  • Gastrins
  • gastrin 17
  • Pepsinogen C
  • Pepsinogen A