Abstract
Abstract Objective: We aimed to assess a serological biopsy using five stomach-specific circulating biomarkers—pepsinogen I (PGI), PGII, PGI/II ratio, anti-Helicobacter pylori (H. pylori) antibody, and gastrin-17 (G-17)—for identifying high-risk individuals and predicting risk of developing gastric cancer (GC). Methods: Among 12112 participants with prospective follow-up from an ongoing population-based screening program using both serology and gastroscopy in China, we conducted a multi-phase study involving a cross-sectional analysis, a follow-up analysis, and an integrative risk prediction modeling analysis. Results: In the cross-sectional analysis, the five biomarkers (especially PGII, the PGI/II ratio, and H. pylori sero-positivity) were associated with the presence of precancerous gastric lesions or GC at enrollment. In the follow-up analysis, low PGI levels and PGI/II ratios were associated with higher risk of developing GC, and both low (<0.5 pmol/L) and high (2.0-4.7 or >4.7 pmol/L) G-17 levels were associated with higher risk of developing GC, suggesting a J-shaped association. In the risk prediction modeling analysis, the five biomarkers combined yielded a C statistic of 0.801 (95% CI=0.787-0.815) and improved prediction beyond traditional risk factors (C statistic from 0.580 to 0.811, P<0.001) for identifying precancerous lesions at enrollment, and higher serological biopsy score based on the five biomarkers at enrollment were associated with higher risk of developing GC during follow-up (P for trend <0.001). Conclusions: A serological biopsy composed of the five stomach-specific circulating biomarkers could be used to identify high-risk individuals for further diagnostic gastroscopy, and to stratify individuals’ risk of developing GC and thus to guide targeted screening/precision prevention. Citation Format: Huakang Tu, Liping Sun, Xiao Dong, Yuehua Gong, Qian Xu, Jingjing Jing, Roberd M. Bostick, Xifeng Wu, Yuan Yuan. A serological biopsy using five stomach-specific circulating biomarkers for gastric cancer risk assessment: a multi-phase study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5304. doi:10.1158/1538-7445.AM2017-5304
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