Gut Liver. 2026;20(2):176-198.

The Role of Serum Pepsinogen Tests for Detecting Gastric Cancer Between Sexes and Among Age Groups.

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제1저자 임선희, 최용훈 · 교신저자 김나영

PMID 41834169 PMC12989666 DOI 10.5009/gnl250494 IF 4.1 소화기내과

소속 (4)

Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center and Healthcare Research Institute, Seoul, Korea.
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Research Center for Sex- and Gender-Specific Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Abstract

Gastric cancer (GC) remains a significant concern worldwide, with a very high incidence in Japan, South Korea, and China. Early diagnosis of GC is important for reducing its mortality; to achieve this, screening of individuals at a high risk for developing GC should include frequent esophagogastroduodenoscopy. Currently, various population-based GC screening strategies are being implemented in South Korea, Japan, and the Matsu region of Taiwan. Many studies have suggested that serum pepsinogens (sPGs) can be used as GC biomarkers in South Korea, China, Europe, and other countries; indeed, Japan first included the sPG test in GC screening prior to 1990. However, while the role of sPGs (particularly type 1) as a marker of atrophic gastritis is well known, studies on the association between sPG levels and GC have mainly focused on the association with intestinal-type GC. Recent studies have demonstrated that sPGII is associated with severe inflammation and proliferation. Specifically, high sPGII levels and Helicobacter pylori positivity are associated with an increased risk of early diffuse-type GC, particularly in young females. In this review, the physiology of sPGs and the usefulness of sPG levels in the detection of intestinal- or diffuse-type GC are discussed in terms of sex and age.

Keywords

Atrophic gastritisHelicobacter pyloriPepsinogensStomach neoplasms

Figures

**Fig. 1** ROC curve of the sPG level in diagnosing gastric adenoma using (A-C) GastroPanel and (D-F) L-TIA testing. A PG I/II ratio of 3 with the L-TIA kit corresponded to 5.3 with the GastroPanel kit. ROC, receiver operating characteristic; sPG, serum pepsinogen; L-TIA, latex-enhanced turbidimetric immunoassay; AUC, area under the curve. Adapted from Choi Y, *et al.* Gut Liver 2025;19:809-820.59

**Fig. 2** Comparison of serum pepsinogen (sPG) levels and histologic features according to *Helicobacter* *pylori* (HP) status. Patients with HP-positivity had higher sPGI (A) and sPGII levels (B) and a lower sPGI/sPGII ratio (C) (all p<0.001). Data are presented as the median±standard errors. Adapted from Baek SM, *et al.* Gut Liver 2020;14:439-449.63

**Fig. 3** Comparison of pepsinogen levels between the GC/dysplasia and control groups before and after HP eradication. HP, *Helicobacter* *pylori*; GC, gastric cancer; PG, pepsinogen. *Indicates statistical significance (p<0.05). Adapted from Noh G, *et al.* J Gastroenterol Hepatol 2020;35:1540-1548, with permission from John Wiley and Sons.66

**Fig. 4** Serum pepsinogen (sPG) levels and sPGI/sPGII ratios in controls, gastric adenoma (GA) patients, and gastric cancer (GC) patients. (A) sPGI levels were highest in controls and decreased in patients with GA and GC; moreover, the levels in intestinal-type GC were significantly lower than those in diffuse-type GC. (B) sPGII levels, meanwhile, were nonsignificantly decreased in patients with GA but increased in GC, and were significantly lower in intestinal-type GC than in diffuse-type GC. (C) Compared with that in the control group, the sPGI/sPGII ratio was significantly reduced in both GA and GC patients, particularly in the intestinal-type GC group. Adapted from Choi Y, *et al.* Gut Liver 2025;19:809-820.59

**Fig. 5** ROC curves of the sPGII level in diagnosing GC. In increasing AUC order, the analyzed groups were as follows: total GC (A), DGC (B), DGC-E (C), DGC-E over 40 years (D), DGC-E under 40 years (E), and DGC-E in females aged under 40 years (F). In the latter group, the AUC was 0.843, the sensitivity was 81%, and the specificity was 90%. ROC, receiver operating characteristic; sPGII, serum pepsinogen type 2; GC, gastric cancer; AUC, area under the curve; DGC, diffuse-type GC; DGC-E, early-stage DGC. Adapted from Lim SH, *et al.* Cancers (Basel) 2025;17:955.107

**Fig. 6** Schematic of the ABC method. Individuals who test negative for both *Helicobacter* *pylori* immunoglobulin G (HPIgG) and serum pepsinogens (sPGs) are classified as Group A; those positive for HPIgG but negative for sPGs, as Group B; those positive for both markers, as Group C; and those negative for HPIgG but positive for sPGs, as Group D. Adapted from Kishikawa H *et al.* Dis Markers. 2015;10:156719.140

그림 출처: PubMed Central 공개 논문 (PMC12989666)

Conflict of interest statement

CONFLICTS OF INTEREST . No potential conflict of interest relevant to this article was reported.

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