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Cancer Epidemiology, Biomarkers &... Jul 2022Gastric cancer lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, a gastric...
BACKGROUND
Gastric cancer lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, a gastric cancer precursor, and may be useful to detect persons at increased risk of gastric cancer.
METHODS
The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted in the United States between 1993 and 2001. ELISA-based pepsinogen tests were conducted on prediagnostic serum samples of 105 PLCO participants who developed gastric cancer and 209 age, sex, and race-matched controls. Pepsinogen positive (PG+) was defined as pepsinogen I ≤ 70 μg/L and pepsinogen I/II ratio ≤3.0. Results of conditional logistic regression models, and sensitivity and specificity, of PG+ for gastric cancer are reported.
RESULTS
Gastric cancer cases were more likely to be PG+ (31.4% vs. 5.5%, P < 0.001) at baseline than controls. Compared to PG-, PG+ was associated with an 8.5-fold increased risk for gastric cancer [95% confidence interval (CI) = 3.8-19.4]. This risk remained significant after adjusting for Helicobacter pylori, family history of gastric cancer, education, smoking, and BMI (aOR, 10.6; 95% CI, 4.3-26.2). In subgroup analysis, PG+ individuals were 11-fold more like to develop non-cardia gastric cancer (OR, 11.1; 95% CI, 4.3-28.8); conversely, they were not significantly more likely to develop cardia gastric cancer (OR, 2.0; 95% CI = 0.3-14.2). PG+ status yielded low sensitivity but high specificity for both noncardia (44.3%; 93.6%) and cardia gastric cancer (5.7%; 97.2%).
CONCLUSIONS
Prediagnostic serum pepsinogen levels from a large, prospective cohort study were associated with risk of gastric cancer, particularly noncardia gastric cancer.
IMPACT
PG status may identify individuals at higher risk of noncardia gastric cancer for targeted screening or interventions. See related commentary by Zhou and Huang, p. 1257.
Topics: Biomarkers; Case-Control Studies; Clinical Trials as Topic; Early Detection of Cancer; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Pepsinogen A; Pepsinogen C; Prospective Studies; Prostate; Stomach Neoplasms; United States
PubMed: 35534235
DOI: 10.1158/1055-9965.EPI-21-1328 -
Journal of Epidemiology Dec 2016
Topics: Antibodies, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Pepsinogen A; Prospective Studies; Stomach Neoplasms
PubMed: 27546709
DOI: 10.2188/jea.JE20160140 -
FEBS Letters Dec 1988Human pepsinogen A3 and A5 have been purified to chromatographic and electrophoretic homogeneity. At pH 2 pepsinogen A3 activates at a much faster rate than pepsinogen...
Human pepsinogen A3 and A5 have been purified to chromatographic and electrophoretic homogeneity. At pH 2 pepsinogen A3 activates at a much faster rate than pepsinogen A5. Leu-23-Lys-24 is the first bond cleaved during activation of pepsinogen A3. This bond is also cleaved in pepsinogen A5, but together with the cleavage of Asp-25-Phe-26. Amino acid sequencing shows that pepsinogen A3 has Glu at position 43, whereas pepsinogen A5 has Lys.
Topics: Amino Acid Sequence; Enzyme Activation; Gastric Mucosa; Humans; Isoenzymes; Kinetics; Molecular Sequence Data; Pepsinogens
PubMed: 3197840
DOI: 10.1016/0014-5793(88)81033-0 -
Immunity, Inflammation and Disease Oct 2023To analyze the difference of serum gastrin-17 (G17) level in healthy people with different sex, age, and body mass index (BMI), to explore the correlation between G17...
BACKGROUND
To analyze the difference of serum gastrin-17 (G17) level in healthy people with different sex, age, and body mass index (BMI), to explore the correlation between G17 and pepsinogen, and to study the influences of Helicobacter pylori (H. pylori) infection and various inflammatory factors on G17 secretion level.
METHODS
A total of 531 subjects who received physical examination in our center from April 2019 to December 2019 were enrolled in the study. All subjects were tested for G17, pepsinogen I (PGI), pepsinogen II (PGII), PGI/PGII ratio (PGR), H. pylori, serum amyloid A (SAA), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The difference of G17 secretion in different subjects and its correlation with PG were analyzed to investigate H. pylori infection and expound the effects of inflammatory indicators on G17.
RESULTS
There was no significant difference in G17 secretion level in people with different sex, age and BMI (p > .05). G17 positively correlated with PGI and PGII, but negatively correlated with PGR. The G17 level of H. pylori-positive subjects was 10.16 ± 12.84, and prominently higher than that of H. pylori-negative subjects (3.27 ± 6.65). SAA and H. pylori infection were the greater risk factors for G17 abnormality among various indicators. CRP and ESR had no effect on G17 abnormality.
CONCLUSIONS
G17 secretion is closely related to PG and H. pylori. Combined screening contributes to early screening of gastrointestinal diseases in normal people or groups at high risk for gastric cancer, but the influence of inflammatory indicators on G17 should be excluded to improve the reliability of the results.
Topics: Humans; Gastric Mucosa; Reproducibility of Results; Gastrins; Pepsinogen A; Pepsinogen C; Physical Examination
PubMed: 37904688
DOI: 10.1002/iid3.993 -
Contrast Media & Molecular Imaging 2022We aim to investigate the therapeutic effect of self-made decoction based on the differences-in-differences (DID) model for treating chronic atrophic gastritis and its... (Randomized Controlled Trial)
Randomized Controlled Trial
We aim to investigate the therapeutic effect of self-made decoction based on the differences-in-differences (DID) model for treating chronic atrophic gastritis and its effect on the gastrin and pepsinogen expression. A total of 166 chronic atrophic gastritis patients treated in our hospital from January 2019 to September 2020 were recruited and randomly assigned to a treatment group and a control group ( = 83 per group). In the control group, patients were given conventional western medicine. In the treatment group, patients were administered self-made decoction besides conventional western medicine. The general data, total effective rate, and histological changes before and after treatment were compared between the two groups. The DID model was utilized to compare the changes in three items of gastric function and traditional Chinese medicine (TCM) syndrome scores at various time points (before treatment and 1, 3, 6, and 12 months after treatment) between the two groups. In the treatment group, 5 cases were lost to follow-up, and 78 cases remained. In the control group, 4 cases were lost to follow-up, and 79 cases remained. The total effective rate in the treatment group (93.59%) was significantly higher than that in the control group (82.28%) ( < 0.05). The histological score was not significantly different between the two groups before treatment ( > 0.05). The histological score at 12 months after treatment was lower than those before treatment in the two groups ( < 0.05). The histological score was lower in the treatment group than that in the control group ( < 0.05). After treatment, the TCM syndrome score and PGR17 level were lower in the treatment group than those in the control group at each time point ( < 0.05). PGI and PGII levels were higher in the treatment group than those in the control group at each time point ( < 0.05). DID regression model showed that TCM syndrome score and PGR17 level decreased by 106.2% and 65.8%, respectively, after treatment in patients with chronic atrophic gastritis ( < 0.05), but the treatment mode was opposite to the overall therapeutic effect in terms of time. The PGI and PGII levels increased by 102.9% and 97.8%, respectively, in patients with chronic atrophic gastritis ( < 0.05), and the treatment mode was the same as the overall therapeutic effect in terms of time. There was no significant difference in the therapeutic effect between the two groups at 1 month after treatment. A significant difference in the therapeutic effect was detected between the two groups at 3 months after treatment, and the difference showed a decreasing trend after 6 months after treatment. Self-made decoction can improve the histological alterations in chronic atrophic gastritis, relieve clinical symptoms, and ameliorate the expression levels of three items of gastric function.
Topics: Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter pylori; Humans; Pepsinogen A
PubMed: 35694708
DOI: 10.1155/2022/1092695 -
Clinical and Translational... Sep 2020Chronic atrophic autoimmune gastritis (CAAG) can lead to the development of gastric neuroendocrine tumors (gNETs) and can be accompanied by other autoimmune diseases....
INTRODUCTION
Chronic atrophic autoimmune gastritis (CAAG) can lead to the development of gastric neuroendocrine tumors (gNETs) and can be accompanied by other autoimmune diseases. This study aimed to determine, in CAAG patients, the association of gNET development, the prevalence of autoimmune diseases other than CAAG, the association of autoimmunity, and gNET development with pepsinogen I, II, gastrin-17, and Helicobacter pylori infection analysis.
METHODS
We determined the prevalence of gNETs and other autoimmune diseases and analyzed pepsinogen I and II, gastrin-17 serum levels, and H. pylori infection in all patients diagnosed with CAAG at our hospital between 2013 and 2017.
RESULTS
A total of 156 patients were studied and in 15.4% was observed concomitant gNET. Approximately 68.6% had at least 1 other autoimmune disease at diagnosis of CAAG. Approximately 60.9% had autoimmune thyroiditis, followed by diabetes (19.9%) and autoimmune polyendocrine syndrome (12.8%). CAAG patients with and without gNET had similar rates of comorbidity with other autoimmune diseases, but the pepsinogen I/II ratio was lower in patients with gNET (1.6 vs 4.5, P = 0.018). Receiver operating characteristic curve analyses identified a pepsinogen I/II ratio <2.3 and gastrin-17 levels >29.6 pmol/L as cutoffs distinguishing CAAG patients with gNET from those without. The combined use of these cutoff correctly identified 16 of the 18 CAAG patients with gNET (P = 0.007). H. pylori infection was observed in 28.7% of cases tested but did not associate with gNET.
DISCUSSION
This study suggests that a low pepsinogen I/II ratio and high gastrin-17 levels characterize patients with CAAG and gNET and confirms the frequent coexistence of CAAG with other autoimmune diseases.
Topics: Adolescent; Adult; Aged; Autoimmune Diseases; Biomarkers; Diagnosis, Differential; Female; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Neuroendocrine Tumors; Pepsinogen A; Pepsinogen C; Prevalence; ROC Curve; Retrospective Studies; Stomach Neoplasms; Young Adult
PubMed: 33094954
DOI: 10.14309/ctg.0000000000000238 -
Alimentary Pharmacology & Therapeutics Apr 2011Gastric acid has an important pathophysiological role in human beings. Numerous methods have been evaluated over the years in an attempt to measure gastric acid and... (Review)
Review
BACKGROUND
Gastric acid has an important pathophysiological role in human beings. Numerous methods have been evaluated over the years in an attempt to measure gastric acid and stomach acidity, to study the role of gastric acid in gastrointestinal diseases in humans and to evaluate the effects of acid suppressing drugs.
AIM
To review methods that have been used to measure gastric acid and gastric acidity.
METHODS
Searches of the electronic databases PUBMED, MEDLINE and EMBASE, were performed with articles restricted to English language and human subjects. References were also identified from the bibliographies of selected articles.
RESULTS
Methods for measuring gastric acid include both invasive and non-invasive techniques. Invasive tests include the conventional gastric acid aspiration tests, gastric pH measurement techniques and endoscopic methods. Non-invasive methods use urinary analysis, breath analysis, serum pepsinogens assay, scintigraphic techniques, impedence tomography and alkaline tide for measurement of gastric acid.
CONCLUSIONS
Several methods of measuring gastric acid exist. Invasive tube tests are uncomfortable and time consuming, whereas most of the non-invasive methods are at best semiquantitative and useful in detecting low or absent acid secretion. Further attempts to explore new methods for measuring gastric acid are therefore warranted.
Topics: Digestion; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Pepsinogens; Reproducibility of Results
PubMed: 21261669
DOI: 10.1111/j.1365-2036.2010.04573.x -
British Journal of Cancer Apr 2003Serum levels of pepsinogen and gastrin are parameters that can be used as biomarkers for gastric mucosa. The aim of this study was to validate these serum biomarkers,...
Serum levels of pepsinogen and gastrin are parameters that can be used as biomarkers for gastric mucosa. The aim of this study was to validate these serum biomarkers, that is pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, and gastrin, as screening tests for precancerous lesions: atrophic chronic gastritis (ACG) or Helicobacter pylori-related corpus-predominant or multifocal atrophy. The study population was comprised of a subsample of 284 patients from the 451 included in the Eurohepygast cohort, between 1995 and 1997. The concentrations of PGA, PGC, and gastrin were measured by radioimmunoassays. Histological diagnosis was the gold standard. Cut-off points were calculated using receiving operator characteristics (ROC) curves. Factors linked to variation of biomarkers were identified using multivariate linear regression. The mean of each biomarker in the sample was: PGA, 77.4 microg x l(-1); PGC, 13.2 microg x l(-1); PGA/PGC, 6.7; and gastrin, 62.4 ng x l(-1). For ACG patients, the areas under the PGA, PGC, PGA/PGC, and gastrin ROC curves were 0.55, 0.62, 0.73, and 0.58, respectively. The best cut-off point for PGA/PGC was 5.6, with sensitivity 65% and specificity 77.9%. For H. pylori-related corpus-predominant or multifocal atrophy, the areas under the respective ROC curves were 0.57, 0.67, 0.84, and 0.69. The best cut-off point for PGA/PGC was 4.7, with sensitivity 77.1% and specificity 87.4%. The results suggested that only the PGA/PGC ratio can be considered as a biomarker for precancerous lesions of the stomach, and may be useful as a screening test.
Topics: Antigens, Bacterial; Bacterial Proteins; Biomarkers; Biopsy; Dyspepsia; Europe; Gastrins; Gastritis; Helicobacter pylori; Humans; Pepsinogen A; Pepsinogen C; Radioimmunoassay
PubMed: 12698190
DOI: 10.1038/sj.bjc.6600877 -
Computational and Mathematical Methods... 2022Gastric cancer pathological biopsy and visual examination have been the gold standard for gastric cancer diagnosis, but their operation is costly, demanding, and risky,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Gastric cancer pathological biopsy and visual examination have been the gold standard for gastric cancer diagnosis, but their operation is costly, demanding, and risky, so it is especially important to find an effective examination method in clinical practice.
AIMS
To investigate the correlation between serum pepsinogen I (PGI), pepsinogen II (PGII), pepsinogen I and II ratio (PGR), IL-6, and TNF- and Helicobacter pylori (Hp) infection in patients with gastric cancer.
MATERIALS AND METHODS
Fifty patients with Hp-infected gastric cancer admitted to the Department of Gastroenterology of our hospital from January 2019 to December 2021 were selected for the study as the observation group, and another 50 patients without Hp-infected gastric cancer were selected as the comparison group to compare the correlation analysis of PGI, PGII, PGR, IL-6, and TNF- with Hp infection between the two groups after admission and treatment.
RESULTS
After measurement, PGI and PGII in the observation group were significantly lower than those in the comparison group, and TNF-, IL-18, and IL-6 in the observation group were significantly higher than those in the comparison group, and the comparative differences were all statistically significant ( < 0.05). The results of multivariate logistic regression model analysis of independent risk factors for gastric cancer showed that IL-18, hs-CRP, and tumor necrosis factor- (TNF-) were risk factors for Hp infection in gastric cancer.
CONCLUSION
The expression of IL-18, hs-CRP, and TNF- factors in Hp-infected gastric cancer patients is correlated. IL-6, IL-18, and TNF- are involved in the entire process from the onset to the development of Hp-positive gastric mucosal inflammation in patients, which is of great value in the diagnosis of gastric cancer and helps to assess the degree of progression and prognosis of gastric cancer.
Topics: C-Reactive Protein; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-18; Interleukin-6; Interleukins; Pepsinogen A; Pepsinogen C; Stomach Neoplasms; Tumor Necrosis Factor-alpha
PubMed: 36158129
DOI: 10.1155/2022/9277847 -
PloS One 2022In Mongolia, gastric cancer morbidity and mortality are high, and more than 80 percent of cases are diagnosed at an advanced stage. This study aimed to evaluate...
In Mongolia, gastric cancer morbidity and mortality are high, and more than 80 percent of cases are diagnosed at an advanced stage. This study aimed to evaluate pepsinogens (PGIs) and gastrin-17 (G-17) levels and to determine the diagnostic performances for gastric cancer and chronic atrophic gastritis among Mongolian individuals. We enrolled a total of 120 subjects, including gastric cancer (40), atrophic gastritis (40), and healthy control (40), matched by age (±2) and sex. Pepsinogen I (PGI), Pepsinogen II (PGII), G-17, and H. pylori IgG levels were measured using GastroPanel ELISA kit (Biohit, Helsinki, Finland). Also, PGI to PGII ratio (PGR) was calculated. For atrophic gastritis, when the optimal cut-off value of PGI was ≤75.07 ng/ml, the sensitivity and specificity were 75% and 50%, respectively; when the optimal cut-off value of PGR was ≤6.25, sensitivity and specificity were 85% and 44.7%, respectively. For gastric cancer, when the optimal cut-off value of PGI was ≤35.25 ng/ml, the sensitivity and specificity were 47.2% and 86.8%, respectively; when the optimal cut-off value of PGR was ≤5.27, sensitivity and specificity were 75% and 60.5%, respectively. Combinations of biomarkers with risk factors could improve diagnostic accuracy (AUC for atrophic gastritis 74.8, 95% CI 64.0-85.7, p<0.001; AUC for gastric cancer 75.5, 95% CI 64.2-86.8, p<0.001). PGI, PGR biomarkers combined with the risk of age, family history of gastric cancer, and previous gastric disease could not be an alternative test for upper endoscopy but might be a supportive method which is identifying individuals at medium- and high risk of gastric cancer and precancerous lesions who may need upper endoscopy.
Topics: Biomarkers; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Pepsinogen A; Pepsinogen C; Stomach Neoplasms
PubMed: 36251649
DOI: 10.1371/journal.pone.0274938