Evaluation of serum markers for gastric cancer and its precursor diseases among high incidence and mortality rate of gastric cancer area
Mongolia has the highest mortality rate of gastric cancer. The early detection of cancer and down-staging screening for high risk patients are essential. Therefore, we aimed to validate serum markers for stratifying patients for further management.
Endoscopy and histological examination were performed to determine high risk and gastric cancer patients. Rapid urease test, culture and histological tests were performed to diagnose Helicobacter pylori infection. Serum pepsinogen (PG) I and II and anti-H. pylori IgG were measured by ELISA. Receiver Operating Characteristic analysis was used to extract the best cut-off point.
Totally 752 non-cancer and 50 consecutive gastric cancer patients were involved. The corpus chronic gastritis (72%: 36/50 vs. 56.4%: 427/752), corpus atrophy (42.0%: 21/50 vs. 18.2%: 137/752) and intestinal metaplasia (IM) (64.0%: 32/50 vs. 21.5%: 162/752) were significantly higher in gastric cancer than non-cancer patients, respectively. Therefore, corpus chronic gastritis, corpus atrophy and IM were considered as high risk disease. The best serum marker to predict the high risk status was PGI/II < 3.1 (sensitivity 67.2%, specificity 61%) and PGI/II further reduced to < 2.2 (sensitivity 66%, specificity 65.1%) together with PGI < 28 ng/mL (sensitivity 70%, specificity 70%) were the best prediction for gastric cancer. The best cut-off point to diagnose H. pylori infection was anti-H. pylori IgG > 8 U/mL. Multivariate analysis showed that anti-H. pylori IgG > 8 U/mL and PGI/II < 3.1 increased risk for high risk status and PGI/II < 3.1 remained to increase risk for gastric cancer.
The serum diagnosis using PGI/II < 3.1 cut-off value is valuable marker to predict high risk patients for population based massive screening.
KeywordsSerum markers Gastric cancer High risk disease Helicobacter pylori Pepsinogen Mongolia
The authors thank the study participants and wish to thank T. Matsuhisa, (A) Battulga, N. Bira, Ts. Byambajav, O. Bolor and (B) Bilguudei for collecting samples.
BG, KO, DD, RS and YY conceived and designed the study; BG, KO, DB, YE, TT and YY contributed by collecting samples; BG and TU performed the experiments; BG and YY contributed to analysis and interpretation; BG and YY drafted the manuscript.
This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (26640114, 15H02657 and 16H05191) (Y. Yamaoka), the Special Coordination Funds for Promoting Science and Technology from the MEXT of Japan (Y. Yamaoka), and National Institutes of Health Grants DK62813 (Y. Yamaoka). B.Gantuya is doctoral student supported by the Japanese Government (Monbukagakusho: MEXT) Scholarship Program for 2014.
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest to disclose.
Human rights statement and informed consent
All procedures followed were in accordance with the ethical standard of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Ethical approval was obtained from the Ethics Committees of Ministry of Health, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia and Oita University Faculty of Medicine, Japan. Informed consents were obtained from all patients for their inclusion in the study.
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