A Serological Biopsy Using Five Stomach-Specific Circulating Biomarkers for Gastric Cancer Risk Assessment: A Multi-Phase Study.
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).



Among 12,112 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.



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 (>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 0.803 (95% confidence interval (CI)=0.789-0.816) 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 scores based on the five biomarkers at enrollment were associated with higher risk of developing GC during follow-up (P for trend <0.001).



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 and precision prevention.
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China.|Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Huakang
H
Tu
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China.
Liping
L
Sun
School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Xiao
X
Dong
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China.
Yuehua
Y
Gong
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China.
Qian
Q
Xu
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China.
Jingjing
J
Jing
Department of Epidemiology, Rollins School of Public Health, and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
Roberd M
RM
Bostick
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Xifeng
X
Wu
Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning, China.
Yuan
Y
Yuan
D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000473:pathology; D005755:Gastrins / Q000097:blood*; D005773:Gastroscopy; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood*; D020115:Pepsinogen C / Q000097:blood*; D011230:Precancerous Conditions / Q000097:blood* / Q000473:pathology; D016016:Proportional Hazards Models; D012372:ROC Curve; D018570:Risk Assessment / Q000379:methods; D013274:Stomach Neoplasms / Q000097:blood* / Q000473:pathology
D000907:Antibodies, Bacterial; D015415:Biomarkers; D005755:Gastrins; C013550:gastrin 17; D020115:Pepsinogen C; D020116:Pepsinogen A