Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis

Abstract

BackgroundHuman pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection.MethodsWe searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I2 statistics and publication bias was assessed using Begg and Mazumdar’s test. Meta-regression and subgroup analyses were performed to explore study heterogeneity.ResultsIn total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60–0.76), 0.73 (95% CI: 0.62–0.82), 2.57 (95% CI: 1.82–3.62), and 0.43 (95% CI: 0.34–0.54), 0.76 (95% CI: 0.72–0.80) and 6.01 (95% CI: 3.69–9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55–0.80), 0.88 (95% CI: 0.77–0.94), 5.80 (95% CI: 3.06–10.99), and 0.35 (95% CI: 0.24–0.51), 0.85 (95% CI: 0.82–0.88) and 16.50 (95% CI: 8.18–33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66–0.75), specificity of 0.79 (95% CI: 0.79–0.80), DOR of 6.92 (95% CI: 4.36–11.00), and AUC of 0.78 (95% CI: 0.72–0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51–0.60), specificity of 0.79 (95% CI: 0.76–0.82), DOR of 6.88 (95% CI: 2.30–20.60), and AUC of 0.77 (95% CI: 0.73–0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52–0.83), specificity of 0.84 (95% CI: 0.68–0.93), DOR of 11.51 (95% CI: 6.14–21.56), and AUC of 0.83 (95% CI: 0.80–0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72–0.85), specificity of 0.89 (95% CI: 0.85–0.93), DOR of 24.64 (95% CI: 6.95–87.37), and AUC of 0.87 (95% CI: 0.81–0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38–0.54), specificity of 0.93 (95% CI: 0.91–0.95), DOR of 19.86 (95% CI: 0.86–456.91), and AUC of 0.86 (95% CI: 0.52–1.00).ConclusionSPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential p...

Detection of gastric atrophy by circulating pepsinogens: A comparison of three assays

“…A 2015 meta-analysis by Huang et al . [18] calculated a pooled 69% (95% CI, 52-83%) sensitivity, 84% (95% CI, 68-93%) specificity and ROC AUC of 0.83 (95% CI, 0.80-0.86) for PgI/PgII. Our results are generally comparable.…”

Management ofHelicobacter pyloriinfection—the Maastricht V/Florence Consensus Report

“…This is characterised by corpus predominant gastritis, gastric atrophy/intestinal metaplasia, hypochlorhydria, and evidence of current or past H. pylori infection. Screening on a population-wide basis by invasive approaches is not feasible but the gastric cancer phenotype can be detected by a combination of non-invasive markers including H. pylori serology and pepsinogen levels (Pgl or Pgl/II ratio) 333 334. Genomic approaches are also promising but require validation in prospective studies 335.…”

Association between receptor interacting serine/threonine kinase 2 polymorphisms and gastric cancer susceptibility

“…However, by serological examination, significant differences of PG I/II ratio between AG+GG genotypes and AA homozygotes were not observed in older patients (age >60 years old), although it was significantly different in younger age groups (age ≤60 years old). Sydney system scores express the severity of gastritis at a biopsy point, whereas PG I/II ratio express the spread of mucosal atrophy (16,26). It has been reported that the significant association between serum and histological atrophy is more strongly observed in the corpus compared with in the antrum (27).…”