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Preventive Medicine Sep 2023Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However,...
Development and validation of LightGBM algorithm for optimizing of Helicobacter pylori antibody during the minimum living guarantee crowd based gastric cancer screening program in Taizhou, China.
Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45-70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control.
Topics: Humans; Stomach Neoplasms; Helicobacter pylori; Pepsinogen A; Early Detection of Cancer; Pepsinogen C; Immunoglobulin G
PubMed: 37419420
DOI: 10.1016/j.ypmed.2023.107605 -
American Journal of Veterinary Research Nov 2002To purify and partially characterize various isoforms of canine pepsinogen (PG) from gastric mucosa.
OBJECTIVE
To purify and partially characterize various isoforms of canine pepsinogen (PG) from gastric mucosa.
SAMPLE POPULATION
Stomachs obtained from 6 euthanatized dogs.
PROCEDURE
Mucosa was scraped from canine stomachs, and a crude mucosal extract was prepared and further purified by use of weak anion-exchange chromatography, hydroxyapatite chromatography, size-exclusion chromatography, and strong anion-exchange chromatography. Pepsinogens were characterized by estimation of molecular weights, estimation of their isoelectric points (IEPs), and N-terminal amino acid sequencing.
RESULTS
Two different groups of canine PG were identified after the final strong anion-exchange chromatography: PG A and PG B. Pepsinogens differed in their molecular weights and IER Pepsinogen B appeared to be a dimer with a molecular weight of approximately 34,100 and an IEP of 4.9. Pepsinogen A separated into several isoforms. Molecular weights for the various isoforms of PG A ranged from 34,200 to 42,100, and their IEPs ranged from 4.0 to < 3.0. The N-terminal amino acid sequence for the first 25 amino acid residues for PG A and B had good homology with the amino acid sequences for these proteins in other species.
CONCLUSIONS AND CLINICAL RELEVANCE
Canine PG B and several isoforms of canine PG A have been purified. Availability of these PGs will facilitate development of immunoassays to measure PG in canine serum as a potential diagnostic marker for gastric disorders in dogs.
Topics: Amino Acid Sequence; Animals; Chromatography, Gel; Chromatography, Ion Exchange; Dogs; Electrophoresis, Polyacrylamide Gel; Gastric Mucosa; Isoelectric Point; Molecular Sequence Data; Molecular Weight; Pepsinogen A; Pepsinogens; Protein Isoforms; Sequence Alignment; Sequence Analysis, Protein
PubMed: 12428671
DOI: 10.2460/ajvr.2002.63.1585 -
Scandinavian Journal of Gastroenterology Feb 2012Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often... (Review)
Review
BACKGROUND AND AIMS
Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers.
METHODS
The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice.
RESULTS
In AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria.
CONCLUSIONS
Stomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach.
Topics: Achlorhydria; Antibodies, Bacterial; Biomarkers; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Mass Screening; Pepsinogen A; Pepsinogen C; Stomach Neoplasms; Vitamin B 12
PubMed: 22242613
DOI: 10.3109/00365521.2011.645501 -
Biomarkers in Medicine 2014Helicobacter pylori infection is a major cause of gastric cancer. Although identifying H. pylori infected subjects is the first approach for delineating the high-risk... (Review)
Review
Helicobacter pylori infection is a major cause of gastric cancer. Although identifying H. pylori infected subjects is the first approach for delineating the high-risk population for gastric cancer, the presence of H. pylori antibodies is not sufficient for gastric cancer screening. Among H. pylori infected subjects, only a minority of infected individuals develop gastric cancer. Serologic markers of H. pylori infection can serve as potential predictors for the development of gastric cancer. Serum or urinary H. pylori antibodies, cytotoxin-associated gene A antibodies, pepsinogen and microRNAs were reported to be associated with precancerous lesions or gastric cancer. In this review, we summarized the utilities and limitations of each strategy.
Topics: Antibodies, Bacterial; Biomarkers, Tumor; Helicobacter Infections; Helicobacter pylori; Humans; MicroRNAs; Pepsinogen A; Stomach Neoplasms
PubMed: 25402582
DOI: 10.2217/bmm.14.72 -
Cellular and Molecular Life Sciences :... Feb 2002Five types of zymogens of pepsins, gastric digestive proteinases, are known: pepsinogens A, B, and F, progastricsin, and prochymosin. The amino acid and/or nucleotide... (Review)
Review
Five types of zymogens of pepsins, gastric digestive proteinases, are known: pepsinogens A, B, and F, progastricsin, and prochymosin. The amino acid and/or nucleotide sequences of more than 50 pepsinogens other than pepsinogen B have been determined to date. Phylogenetic analyses based on these sequences indicate that progastricsin diverged first followed by prochymosin, and that pepsinogens A and F are most closely related. Tertiary structures, clarified by X-ray crystallography, are commonly bilobal with a large active-site cleft between the lobes. Two aspartates in the center of the cleft, Asp32 and Asp215, function as catalytic residues, and thus pepsinogens are classified as aspartic proteinases. Conversion of pepsinogens to pepsins proceeds autocatalytically at acidic pH by two different pathways, a one-step pathway to release the intact activation segment directly, and a stepwise pathway through a pseudo-pepsin(s). The active-site cleft is large enough to accommodate at least seven residues of a substrate, thus forming S4 through S'3 subsites. Hydrophobic and aromatic amino acids are preferred at the P1 and P'1 positions. Interactions at additional subsites are important in some cases, for example with cleavage of kappa-casein by chymosin. Two potent naturally occurring inhibitors are known: pepstatin, a pentapeptide from Streptomyces, and a unique proteinous inhibitor from Ascaris. Pepsinogen genes comprise nine exons and may be multiple, especially for pepsinogen A. The latter and progastricsin predominate in adult animals, while pepsinogen F and prochymosin are the main forms in the fetus/infant. The switching of gene expression from fetal/infant to adult-type pepsinogens during postnatal development is noteworthy, being regulated by several factors, including steroid hormones.
Topics: Amino Acid Sequence; Animals; Chymosin; Enzyme Precursors; Evolution, Molecular; Gene Expression Regulation, Developmental; Humans; Models, Molecular; Molecular Sequence Data; Pepsinogen C; Pepsinogens; Primates; Protease Inhibitors; Sequence Homology, Amino Acid; Terminology as Topic; Transcription, Genetic
PubMed: 11915945
DOI: 10.1007/s00018-002-8423-9 -
Frontiers in Cellular and Infection... 2022Association of gastric atrophy or cancer with levels of serum pepsinogens, gastrin-17 and anti- IgG antibody have been extensively studied. However, the association of...
BACKGROUND
Association of gastric atrophy or cancer with levels of serum pepsinogens, gastrin-17 and anti- IgG antibody have been extensively studied. However, the association of serum pepsinogen and gastrin-17 with infection has not been studied in a large population.
AIM
To investigate the impact of infection on serum levels of pepsinogens and gastrin-17.
METHODS
A total of 354, 972 subjects who underwent health check-ups were included. Serum levels of pepsinogens and gastrin-17 were measured using the enzyme-linked immunosorbent assay infection was detected using C-urea breath test (UBT). Multivariable logistic regression analysis was used to investigate the association of serum pepsinogen and gastrin-17 with infection.
RESULTS
prevalence was 33.18% in this study. The mean levels of pepsinogens and gastrin-17 were higher, while the mean pepsinogen-I/II ratio were lower among -positive than -negative subjects. In -positive subjects, pepsinogen and gastrin-17 levels correlated positively, whereas the pepsinogen-I/II ratio correlated negatively with UBT values (e.g., the mean serum level of pepsinogen-I in subjects with UBT values in the range of 100-499dpm, 500-1499dpm, and ≥1500dpm was 94.77 ± 38.99, 102.77 ± 43.59, and 111.53 ± 47.47 ng/mL, respectively). Compared with -negative subjects, the adjusted odds ratio (aOR) of having pepsinogen-I ≤ 70 ng/mL in the three -positive but with different UBT value groups was 0.31 (<0.001), 0.16 (<0.001), and 0.08 (<0.001), respectively; while the aOR of having G-17>5.70 pmol/L was 4.56 (<0.001), 7.43 (<0.001), and 7.12 (<0.001). This suggested that -positive subjects with higher UBT values were less likely to have pepsinogen-I ≤70 ng/mL (a serum marker for gastric atrophy), but more likely to have gastrin-17 >5.70 pmol/L (a marker for peptic ulcer).
CONCLUSIONS
-positive subjects with higher UBT values are unlikely to have gastric atrophy, but may have greater risk of severe gastritis or peptic ulcers. Our study suggests that -positive patients with high UBT values may benefit the most from eradication.
Topics: Atrophy; Biomarkers; Breath Tests; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogen A; Urea
PubMed: 36051244
DOI: 10.3389/fcimb.2022.980399 -
PloS One 2014To identify high-risk groups for gastric cancer in presumptively healthy populations, several studies have investigated the predictive ability of the pepsinogen test, H.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To identify high-risk groups for gastric cancer in presumptively healthy populations, several studies have investigated the predictive ability of the pepsinogen test, H. Pylori antibodies, and a risk-prediction model based on these two tests. To investigate whether these tests accurately predict gastric cancer development, we conducted a systematic review and meta-analysis.
METHODS
PubMed and other electronic databases were searched for cohort studies published in English or Japanese from January 1985 through December 2013. Six reviewers identified eligible studies, and at least two investigators extracted data on population and study-design characteristics, quality items, and outcomes of interest. Meta-analyses were performed on non-overlapping studies.
RESULTS
Nine prospective cohorts from Eastern Asia reported in 12 publications, including 33,741 asymptomatic middle-aged participants of gastric cancer screening, were eligible. For discriminating between asymptomatic adults at high and low risk of gastric cancer, the pepsinogen test (summary hazard ratio [HR], 3.5; 95% confidence interval [CI], 2.7-4.7; I2 = 0%) and H. pylori antibodies (summary HR, 3.2; 95% CI, 2.0-5.2; I2 = 0%) were statistically significant predictors as standalone tests. Although the risk-prediction model was in general moderately accurate in separating asymptomatic adults into four risk groups (summary c-statistic, 0.71; 95% CI: 0.68-0.73; I2 = 7%), calibration seemed to be poor. The study validity was generally limited.
CONCLUSIONS
The serum pepsinogen test, H. pylori antibodies, and the four-risk-group model for predicting gastric cancer development seem to have the potential to stratify middle-aged presumptively healthy adults. Future research needs to focus on comparative studies to evaluate the impact of screening programs adopting these tests. Also, validation, preferably with model updating, is necessary to see whether the current model performance is transferable to different populations.
Topics: Antibodies, Bacterial; Asian People; Asia, Eastern; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogen A; Stomach Neoplasms
PubMed: 25314140
DOI: 10.1371/journal.pone.0109783 -
World Journal of Gastroenterology Feb 2014To summarize the current views and insights on associations between Helicobacter pylori (H. pylori)-related chronic gastritis and colorectal neoplasm, we reviewed recent... (Review)
Review
To summarize the current views and insights on associations between Helicobacter pylori (H. pylori)-related chronic gastritis and colorectal neoplasm, we reviewed recent studies to clarify whether H. pylori infection/H. pylori-related chronic gastritis is associated with an elevated risk of colorectal neoplasm. Recent studies based on large databases with careful control for confounding variables have clearly demonstrated an increased risk of colorectal neoplasm associated with H. pylori infection. The correlation between H. pylori-related chronic atrophic gastritis (CAG) and colorectal neoplasm has only been examined in a limited number of studies. A recent large study using a national histopathological database, and our study based on the stage of H. pylori-related chronic gastritis as determined by serum levels of H. pylori antibody titer and pepsinogen, indicated that H. pylori-related CAG confers an increased risk of colorectal neoplasm, and more extensive atrophic gastritis will probably be associated with even higher risk of neoplasm. In addition, our study suggested that the activity of H. pylori-related chronic gastritis is correlated with colorectal neoplasm risk. H. pylori-related chronic gastritis could be involved in an increased risk of colorectal neoplasm that appears to be enhanced by the progression of gastric atrophy and the presence of active inflammation.
Topics: Animals; Chronic Disease; Colonic Neoplasms; Disease Progression; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Pepsinogen A; Risk Factors
PubMed: 24587623
DOI: 10.3748/wjg.v20.i6.1485 -
The Journal of International Medical... Mar 2020Diagnosing gastric cancer (GC) at early stages is important for reducing its mortality. This study evaluated the diagnostic value of serum pepsinogen (PG) I, PGII, and...
OBJECTIVE
Diagnosing gastric cancer (GC) at early stages is important for reducing its mortality. This study evaluated the diagnostic value of serum pepsinogen (PG) I, PGII, and gastrin-17 (G17) levels in screening for early-stage GC.
METHODS
Serum levels of PGI, PGII, and G17 were measured in patients with upper digestive tract symptoms or GC family histories, and the PGI to PGII ratio (PGR) was calculated. Receiver operator characteristic curves were used to determine the thresholds of PGI, PGR, and G17 for GC diagnosis.
RESULTS
Among the 949 patients examined by gastroscopy, 13 (1.37%) had GC, including five cases of early-stage GC and eight cases of progressive GC. PGI, PGR, and G17 showed good specificity and sensitivity for early-stage and progressive GC. The optimal thresholds of PGI, G17, and PGR were 71.85 μg/L, 15.65 pmol/L and 5.04 for the diagnosis of early-stage GC, respectively, and were 42.55 μg/L, 20.55 pmol/L, and 2.79 for the diagnosis of progressive GC, respectively.
CONCLUSION
Combining PG and G17 serum levels with gastroscopy could be a promising approach to screen for early-stage GC.
Topics: Area Under Curve; Disease Progression; Early Detection of Cancer; Ethnicity; Gastrins; Gastroscopy; Humans; Male; Middle Aged; Neoplasm Staging; Pepsinogen A; Pepsinogen C; ROC Curve; Stomach Neoplasms
PubMed: 32228342
DOI: 10.1177/0300060520914826 -
Journal of Clinical Pathology Apr 1995To investigate the immunohistochemical expression and the serum concentrations of pepsinogen I and II in different histological types of gastric cancer as compared with... (Comparative Study)
Comparative Study
AIMS
To investigate the immunohistochemical expression and the serum concentrations of pepsinogen I and II in different histological types of gastric cancer as compared with other gastric disorders.
METHODS
Formalin fixed, paraffin wax embedded tissue specimens of 38 gastric cancers obtained from surgical cases were used for the immunohistochemical studies performed with the avidin-biotin complex method using monoclonal antibodies against purified pepsinogen I and II. Pepsinogen concentrations from serum obtained from the above patients, from patients with various other gastric disorders, and from normal controls were measured with a rapid non-radioactive one step enzyme linked immunosorbent assay (ELISA).
RESULTS
Eight of 38 (21%) and seven of 38 (18%) gastric carcinomas showed immunoreactivity to pepsinogen I and pepsinogen II, respectively, without any correlation to histological classification or differentiation. Decreased pepsinogen I concentrations and low pepsinogen I:II ratios were found specifically in cases of gastric carcinoma and polyp, in good accordance with the immunohistochemical results.
CONCLUSIONS
Low serum pepsinogen I concentrations and a low pepsinogen I:II ratio are predictive of gastric neoplasia, correlating with low tissue immunoreactivity to monoclonal antibodies raised against pepsinogen I and II. For mass screening of gastric disease including carcinoma, ELISA using a one step immunoassay performed in the present study is a rapid and reliable non-radioactive method of detecting serum pepsinogen. In addition, immunohistochemical studies showed that pepsinogen production may be increased or diminished as a result of tumour histogenesis, depending on the area of origin and the processes of cell transformation and dedifferentiation.
Topics: Biomarkers, Tumor; Blotting, Western; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Gastritis; Humans; Immunoenzyme Techniques; Pepsinogens; Peptic Ulcer; Polyps; Stomach Neoplasms
PubMed: 7615858
DOI: 10.1136/jcp.48.4.364