Role of Serum Pepsinogen II and Helicobacter pylori Status in the Detection of Diffuse-Type Early Gastric Cancer in Young Individuals in South Korea

Abstract

Background/aims: The utility of serum pepsinogen (sPG) I and the sPGI/II ratio as biomarkers for screening individuals with gastric cancer (GC) has not been established in Korea. The aim of this study was to define the role of sPG, especially sPGII, in GC screening.

Methods: This study enrolled 2,940 subjects, including patients with GC (n=1,124) or gastric dysplasia (n=353) and controls (n=1,463). Tests to determine sPG levels and Helicobacter pylori (HP) infection status were performed. Area under the curve and receiver operating characteristic curve were calculated to identify the optimal cutoff values for sPG. The usefulness of sPG levels for the detection of GC and gastric dysplasia was validated by multivariate logistic regression.

Results: The sPGI/II ratio was associated with the risk of gastric dysplasia and advanced-stage intestinal-type GC (IGC). In contrast, sPGII was associated with the risk of early-stage diffuse-type GC (DGC). Significantly higher risk was indicated by an sPGI/II ratio <3 for gastric dysplasia and advanced-stage IGC and by sPGII levels ≥20 µg/L for early-stage DGC. Positive HP status showed a stronger association with DGC than with IGC. When sPGII level and HP status were combined, the prevalence of DGC was higher in the ≥20 µg/L sPGII and HP-positive group. Age younger than 40 years was strongly related to early-stage DGC, especially in females (odds ratio, 21.00; p=0.006).

Conclusions: sPGII ≥20 ng/mL and positive HP status suggest a risk of early-stage DGC, particularly in young adult females in South Korea.

Keywords: Diffuse type; Helicobacter pylori; Pepsinogen; Stomach neoplasms.

Fig. 1

Study algorithm for the enrollment of the gastric cancer, dysplasia and control groups. MALT, mucosa-associated lymphoid tissue; GIST, gastrointestinal stromal tumor.

Fig. 2

Comparison of serum pepsinogen (sPG) levels and histologic features with respect to Helicobacter pylori (HP) status. HP-positive patients had higher sPGI (A) and sPGII levels (B) and a lower sPGI/II ratio (C) (all p<0.001). OLGA/OLGIM stage, an indicator of atrophic gastritis and intestinal metaplasia, was higher in HP-positive patients (D). Data are presented as the number (%) or median±standard error. OLGA, operative link on gastritis atrophy; OLGIM, operative link on gastric intestinal metaplasia.

Fig. 3

Receiver operating characteristic curve and corresponding AUC of sPGII for the diagnosis of gastric cancer (GC). The AUC for sPGII did not show significant sensitivity and specificity for total GC (A) and DGC (B). However, when the patients with early DGC were grouped with age 40 years as the cutoff, sPGII showed significantly higher diagnostic power for patients with early-stage DGC under 40 years of age (AUC 0.766, 75.0% sensitivity, 74.2% specificity) (D) than those 40 years or older (C). AUC, area under the curve; sPG, serum pepsinogen; DGC, diffuse gastric cancer.