Pepsinogen and Helicobacter pylori: Serum biomarkers for gastric cancer risk in a diverse United States population

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Abstract

Background

Serum Pepsinogen (PG) and Helicobacter pylori (Hp) have potential as biomarkers to identify persons at high risk for gastric cancer (GC) in low incidence populations. We explored the use of these biomarkers in a diverse US population.

Methods

Single institution study using serum samples from 32 newly diagnosed GC (before treatment) and 60 non-cancer participants. ELISA-based PG-I, PG-II, Hp IgG, and Hp virulence seromarker (CagA, VacA) tests were conducted to examine differences between GC and non-GC participants.

Results

Median age was 58 (IQR 48–68); 56 % were females; 30.1 % were white, 14.8 % black, 28.7 % Hispanic, 6.1 % Asian and 18.2 % other/unknown race/ethnicity. Median values of Hp (47.9 vs 12.6 U/mL, p = 0.003) and pepsinogen ratio (PGR=PGI/PGII) (4.0 vs 7.5, p = 0.003) differed between GC and non-GC. Performance of pepsinogen tests using “standard” cut-offs (PGI ≤ 70 ng/mL and PGR ≤ 3) were highly specific (91.7 %), but not sensitive (34.4 %), while Hp IgG test using “standard” cut-off (≥ 30 U/mL) was sensitive (78.8 %), but less specific (41.2 %). Optimized cut-off values identified in our population using Youden’s Index were PGR ≤ 5.2 and Hp ≥ 17.5 U/mL. Using a combination of these values resulted in a significant increase in test sensitivity (87.9 %) with lower specificity (50.8 %).

Conclusion

The combination of pepsinogens and Hp show promise as biomarkers of GC risk in a racially and ethnically diverse US population. Optimal biomarker cut-off points for US populations may differ from those established in East Asia. By adjusting cut-offs there is potential to design GC risk stratification tools tailored specifically for the diverse population within the US.

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胃蛋白酶原和幽门螺旋杆菌:美国不同人群胃癌风险的血清生物标志物
背景血清胃蛋白酶原 (PG) 和幽门螺旋杆菌 (Hp) 有可能作为生物标记物来识别低发病率人群中的胃癌 (GC) 高危人群。我们探讨了这些生物标记物在美国不同人群中的使用情况。方法单个机构研究使用 32 名新诊断为 GC(治疗前)和 60 名非癌症参与者的血清样本。结果平均年龄为 58 岁(IQR 48-68);56% 为女性;30.1% 为白人,14.8% 为黑人,28.7% 为西班牙裔,6.1% 为亚裔,18.2% 为其他/未知种族/族裔。胃蛋白酶中位值(47.9 vs 12.6 U/mL,P = 0.003)和胃蛋白酶原比率(PGR=PGI/PGII)(4.0 vs 7.5,P = 0.003)在胃癌和非胃癌之间存在差异。使用 "标准 "临界值(PGI ≤ 70 ng/mL,PGR ≤ 3)进行胃蛋白酶原检测的特异性很高(91.7%),但灵敏度不高(34.4%),而使用 "标准 "临界值(≥ 30 U/mL)进行肝IgG检测的灵敏度较高(78.8%),但特异性较低(41.2%)。根据尤登指数(Youden's Index),在我国人群中确定的最佳临界值为 PGR ≤ 5.2 和 Hp ≥ 17.5 U/mL。结论胃蛋白酶原和 Hp 的组合有望成为美国种族和民族多样化人群中 GC 风险的生物标志物。美国人群的最佳生物标志物截断点可能与东亚地区的截断点不同。通过调整临界点,有可能设计出专门针对美国不同人群的 GC 风险分层工具。
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