Serum Pepsinogen as a Biomarker of Gastrointestinal Stromal Tumors (GIST) in Stomach

Background: No biomarker was identified for gastric GISTs(GG) detection. We first observed that glands surrounding GG are regionally atrophic. We hypothesize that this local atrophy may mildly reduce pepsinogen Ⅰ(PGⅠ) but the PGⅠ/PGII ratio remains normal. To test our hypothesis, a retrospective analysis was conducted to evaluate the diagnostic efficiency of PG in GG detection. Methods: We retrospectively analyzed a cohort of consecutive GG and gastric cancer(GC) patients at our center. Pathologic confirmed GG patients and GC patients with tested PG levels before medical intervention were included. Three criteria were assessed: 1.Serum PGI≤70ng/ml; 2.Positive-Gastric-GIST-PG(PGⅠ≤70 ng/ml and PGI/PGII ratio>3.0); and 3.Positive-Gastric-GIST-PG-CEA(Positive-Gastric-GIST-PG plus normal CEA). Sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV) and overall accuracy(OA) were calculated. A Chi-square test was applied to detect the differences. Results: After screened 562 GG and 1090 GC, 100 GG and 174 GC samples were included. For PGI≤70ng/ml, the Positive-Gastric-GIST-PG and the Positive-Gastric-GIST-PG-CEA criteria discriminating GG from GC, the sensitivities were 75%(95%CI 66-82),70%(60-78) and 68%(58-76), respectively; the specificities were 50%(43-57), 70%(62-76), and 78%(71-83), respectively; the PPV were 46%(39-54), 57%(48-65), and 64%(55-73), respectively; the NPV were 78%(69-84), 80%(73-86), 81%(74-86), respectively; and the OA were 59%(53-65), 70%(64-75), and 74%(69-79), respectively. There was statistic difference in sensitivities between GG and GC for Positive-Gastric-GIST-PG-CEA criterion(68% for GG vs. 22% for GC, P<0.0001). Conclusion: Serum PGs are useful for both detecting GG and distinguishing GG from GC. Integrating our criteria into current PG test scheme of gastric precancerous screening will be helpful for early GG detection without additional economic expense.