Accuracy of screening for gastric cancer using serum pepsinogen concentrations.
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ABSTRACT:
SUBMITTER: Kitahara F
PROVIDER: S-EPMC1727514 | biostudies-other | 1999 May
REPOSITORIES: biostudies-other
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Project description:Pepsinogen (PG) II (PGII) is a serological marker used to estimate the risk of gastric cancer but how PGII expression is regulated is largely unknown. It has been suggested that PGII expression, from the PGC (Progastricsin) gene, is regulated by microRNAs (miRNA), but how PGII levels vary with Helicobacter pylori (H. pylori) infection and miRNAs genotype remains unclear. Serum levels of PGI and PGII were determined in 80 patients with gastric cancer and persons at risk for gastric cancer (74 first-degree relatives of patients, 62 patients with autoimmune chronic atrophic gastritis, and 2 patients with dysplasia), with and without H. pylori infection. As control from the general population, 52 blood donors were added to the analyses. Associations between PGII levels and genetic variants in PGC and miRNA genes in these groups were explored based on H. pylori seropositivity and the risk for gastric cancer. The two-dimensional difference in gel electrophoresis (2D-DIGE) and the NanoString analysis of messenger RNA (mRNAs) from gastric cancer tissue were used to determine the pathways associated with increased PGII levels. PGII levels were significantly higher in patients with gastric cancer, and in those with H. pylori infection, than in other patients or controls. A PGI/PGII ratio ≤ 3 was found better than PGI < 25 ng/mL to identify patients with gastric cancer (15.0% vs. 8.8%). For two genetic variants, namely rs8111742 in miR-Let-7e and rs121224 in miR-365b, there were significant differences in PGII levels between genotype groups among patients with gastric cancer (p = 0.02 and p = 0.01, respectively), but not among other study subjects. Moreover, a strict relation between rs9471643 C-allele with H. pylori infection and gastric cancer was underlined. Fold change in gene expression of mRNA isolated from gastric cancer tissue correlated well with polymorphism, H. pylori infection, increased PGII level, and pathway for bacteria cell entry into the host. Serum PGII levels depend in part on an interaction between H. pylori and host miRNA genotypes, which may interfere with the cut-off of PGI/PGII ratio used to identify persons at risk of gastric cancer. Results reported new findings regarding the relation among H. pylori, PGII-related host polymorphism, and genes involved in this interaction in the gastric cancer setting.
| S-EPMC7827830 | biostudies-literature
Project description:BackgroundPepsinogens (PGs) can be used for gastric cancer (GC) screening, but the cutoff levels vary among studies, and PG levels are influenced by numerous factors. The aim of this article is to examine the diagnostic value of PG levels and Helicobacter pylori (Hp) status for GC and atrophic gastritis screening in asymptomatic individuals undergoing health checkup in China.Patients and methodsThis was a multicenter cross-sectional study of subjects who underwent health checkup from 10/2016 to 10/2018 at nine International Healthcare Centers in China. All participants underwent gastroscopy and pathological examination, serum PG, 13C-urea breath test, and/or Hp serological current infection marker rapid test, all on the same day. PG-related parameters were analyzed in different Hp subgroups and regions.ResultsThe patients were grouped as non-atrophic (NAG, n = 1,590), mild to moderate atrophic (MAG, n = 273), severe atrophic (SAG, n = 49), and GC (n = 10). The serum PG levels in these groups decreased with increasing pathological severity. In the same pathological groups, PGI and PGII levels were higher in the Hp-positive subgroup, while PGR (PGI/PGII ratio) was lower (P < 0.05). The best cutoff values for atrophy diagnosis were PGI ≤73.1 ng/ml and PGR ≤9.8, for severe atrophy were PGI ≤63.9 ng/ml and PGR ≤9.09, and for GC was PGR ≤4.7 (all P < 0.05 and area under the curve >0.7). The cutoff points varied with Hp status and China regions.ConclusionSerum PG levels might be used for the screening of gastric atrophic gastritis lesions. The results suggest that different cutoff values should possibly be used in different Hp status groups and geographical regions, but it will have to be validated in future studies. Future studies should also examine the value of PG levels for GC detection.
| S-EPMC8421685 | biostudies-literature
Project description:We examined the development of gastric cancer risk screening, from rat pepsinogen studies in an experimental rat gastric carcinogenesis model induced with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and human pepsinogen studies in the 1970s and 1980s to the recent "ABC method" for human gastric cancer risk screening. First, decreased expression or absence of a major pepsinogen isozyme, PG1, was observed in the rat gastric mucosa from the early stages of gastric carcinogenesis to adenocarcinomas following treatment with MNNG. In the 1980s, decreases in PGI in the human gastric mucosa and serum were identified as markers of atrophic gastritis. In the 1990s, other researchers revealed that chronic infection with Helicobacter pylori (Hp) causes atrophic gastritis and later gastric cancer. In the 2000s, a gastric cancer risk screening method combining assays to detect serum anti-Hp IgG antibody and serum PGI and PGII levels, the "ABC method", was established. Eradication of Hp and endoscopic follow-up examination after the ABC method are recommended to prevent gastric cancer.
| S-EPMC8553520 | biostudies-literature
Project description:BACKGROUND:This study aimed to explore the diagnostic value of serum miR-101-3p combined with pepsinogen (PG) on early diagnosis of gastric cancer (GC). METHODS:A total of 61 atrophic gastritis (AG) and 86 GC patients, and 50 healthy volunteers were enrolled. The serum expression of miR-101-3p was measured by qRT-PCR. The serum content of carcinoembryonic antigen (CEA) was measured by Electrochemiluminescence immunoassay. The serum contents of PGI and PGII were measured by Enzyme linked immunosorbent assay. The diagnostic value of serum markers on AG and GC was analyzed by receiver operating characteristic (ROC) analysis. RESULTS:The expression of miR-101-3p, the content of PGI and the ratio of PGI/II were significantly decreased, and the content of PGII was significantly increased in AG patients compared with those in normal controls. The changes of the above serum indicators were more obvious in GC patients than those in AG patients. The content of CEA was significantly higher in GC patients than that in AG patients. In addition, the expression of miR-101-3p was negatively associated with the submucosal infiltration in GC patients. MiR-101-3p exhibited high diagnostic value on AG (AUC 0.8493, sensitivity 80.33%, specificity 80%) and GC (AUC 0.8749, sensitivity 72.09%, specificity 86.49%). MiR-101-3p?+?PGI?+?PGI/II (AUC 0.856, sensitivity 80.23%, specificity 77.05%) exhibited a high diagnostic value in distinguishing between AG and GC. CONCLUSIONS:MiR-101-3p was a potential diagnostic marker for AG and GC. MiR-101-3p?+?PGI?+?PGI/II was effective in distinguishing between AG and GC.
| S-EPMC7011268 | biostudies-literature
Project description:ObjectiveThe serum pepsinogen test has limitation in its predictive power as a noninvasive biomarker for gastric cancer screening. We aimed to investigate whether the combination of TFF3 and pepsinogen could be an effective biomarker for the detection of gastric cancer even in the early stages.MethodsIn total, 281 patients with early gastric cancer (EGC), who underwent endoscopic submucosal dissection in Korea, and 708 healthy individuals from Japan were enrolled in the derivation cohort. The validation cohort included 30 Korean patients with EGC and 30 Korean healthy control blood donors. Serum TFF3 levels were examined using enzyme-linked immunosorbent assay.ResultsUsing a cutoff of 6.73 ng/mL in the derivation cohort, the sensitivity of the combination of tests for EGC detection was superior (87.5%) to that of TFF3 (80.4%) or pepsinogen test alone (39.5%). Similarly, in the validation cohort, the sensitivity of TFF3 plus pepsinogen was higher (90.4%) than that of TFF3 (80.0%) or pepsinogen test alone (33.3%).ConclusionThe combination of serum TFF3 and pepsinogen is a more effective noninvasive biomarker for gastric cancer detection compared with pepsinogen or TFF3 alone, even in EGC. This trial is registered with NCT03046745.
| S-EPMC5994275 | biostudies-literature
Project description:BACKGROUND:Serum pepsinogen 1 (SPG1) and anti-Helicobacter pylori serology have been used for gastric risk stratification in Asia. AIM:To assess utility of these markers in a Western population. METHODS:SPG1 measurements were available for 21 895 Finnish male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We used Cox proportional hazards models adjusted for potential confounders to estimate gastric cancer hazard ratios (HR) and 95% confidence intervals (95% CI) for low SPG1 (<25 ?g/L). In a subset (n = 3555) with anti-H. pylori serology, these markers jointly defined the following: Group A (H. pylori[-], SPG1[normal]; reference group), Group B (H. pylori[+], SPG1[normal]), Group C (H. pylori[+], SPG1[low]) and Group D (H. pylori[-], SPG1[low]). Odds ratios (ORs) and 95% CI were calculated using multivariate logistic regression. RESULTS:There were 329 gastric cancers diagnosed an average of 13.9 years after baseline. Pre-diagnostic low SPG1 was significantly associated with increased gastric cancer risk (HR 2.68, 95% CI 1.99-3.61). Among subjects with both SPG1 and H. pylori serology, groups B, C and D had increased gastric cancer ORs (95% CI) of 1.79 (1.21-2.64), 3.85 (2.36-6.28) and 6.35 (2.20-18.34), respectively. CagA seropositives had significantly higher ORs than CagA seronegatives within group B (Pheterogeneity = 0.01). For groups B and C, repeat SPG1 level at 3 years did not further stratify gastric cancer risk. CONCLUSIONS:Low SPG1 was associated with increased gastric cancer risk in our large Finnish cohort. A single measurement of SPG1 along with H. pylori whole cell and CagA serology provides potentially useful prediction of gastric cancer risk.
| S-EPMC5776724 | biostudies-literature
Project description:AimTo study the role of an insertion/deletion polymorphism in the pepsinogen C (PGC) gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastric lesions.MethodsThe study was performed with 99 samples of known gastric lesions and 127 samples without evidence of neoplastic disease. PCR was employed and the 6 polymorphic alleles were amplified: Allele 1 (510 bp), Allele 2 (480 bp), Allele 3/4 (450/460 bp), Allele 5 (400 bp) and Allele 6 (310 bp).ResultsOur results revealed that Allele 6 carriers seemed to have protection against the development of any gastric lesion (OR = 0.34; P<0.001), non-dysplastic lesions associated with gastric adenocarcinoma such as atrophy or intestinal metaplasia (OR = 0.28; P<0.001) or invasive GC (OR = 0.39; P = 0.004).ConclusionOur study reveals that the Allele 6 carrier status has a protective role in the development of gastric lesions, probably due to its association with higher expression of PGC. Moreover, the frequency of Allele 6 carriers in the control group is far higher than that obtained in Asian populations, which might represent a genetic gap between Caucasian and Asian populations.
| S-EPMC4087408 | biostudies-literature
Project description:BackgroundTo 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.MethodsPubMed 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.ResultsNine 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.ConclusionsThe 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.
| S-EPMC4196955 | biostudies-literature
Project description:BackgroundSerum pepsinogen has been approved and used widely as an effective biomarker in diagnosis of atrophic gastritis and gastric cancer; however, its validity and appropriate cut-off values vary among different populations. This study aimed to initially assess the diagnostic value of the serum pepsinogen in diagnosis of moderate and severe atrophic gastritis for Vietnamese population.Materials and methodsA cross-sectional study enrolled 273 participants from June 2008 to November 2019. All participants underwent a gastroscopy procedure and three tests including serum PG test, pathology test, and Hp-Igg Elisa test. The Kimura-Takemoto classification and OLGA system were used to classify the mild versus moderate-severe atrophic gastritis. Receiver Operating Characteristic curve was used to assess the value of PGI, PGII and PGR.ResultsBased on Kimura-Takemoto classification, the AUC of PGI and PGR was 0.635 (p = 0.008, 95% CI 0.554-0.716) and 0.766 (p < 0.001, 95% CI 0.676-0.857) respectively. The best cut-off values were PGI ≤69.0 and PGR ≤4.6 (sensitivity: 73%, specificity: 83.9%, positive predictive value: 41.5%, negative predictive value: 95.2%, accuracy: 82.4%). According to the OLGA system, the AUC of PGI and PGR was 0.612 (p = 0.004, 95% CI 0.540-0.684) and 0.689 (p < 0.001, 95% CI 0.621-0.758) respectively. The best cut-off values were PGI ≤63.5 and PGR ≤5.2 (sensitivity: 49.4%, specificity: 82.1%, positive predictive value: 52.1%, negative predictive value: 80.5%, accuracy: 72.9%).ConclusionsThe serum pepsinogen II and pepsinogen I/II ratio had reliable diagnostic value for screening of moderate and severe atrophic gastritis among Vietnamese population. Further research was recommended to focus on larger scale to improve the diagnostic yield and to continue finding the cut-off values for diagnosis of gastric cancer among Vietnamese population.
| S-EPMC9207076 | biostudies-literature
Project description:BackgroundThere is little information regarding whether the combination of Helicobacter pylori (H. pylori) antibody and serum pepsinogen (sPG), which is a marker of the degree of atrophic gastritis, has a discriminatory ability for detecting incident gastric cancer. We examined this issue in a long-term prospective cohort study of a Japanese population.MethodsA total of 2446 Japanese community-dwelling individuals aged ≥40 years were stratified into four groups according to baseline H. pylori serological status and sPG: Group A (H. pylori[-], sPG[-]), Group B (H. pylori[+], sPG[-]), Group C (H. pylori[+], sPG[+]), and Group D (H. pylori[-], sPG[+]), and participants were followed up prospectively for 20 years.ResultsDuring the follow-up, 123 subjects developed gastric cancer. Compared with that in Group A, the cumulative incidence of gastric cancer was significantly increased in Groups B, C, and D, whereas no significant difference was found between Groups C and D. The multivariable-adjusted risk of gastric cancer was significantly increased in Group B (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.62-10.28) and in Groups C and D combined (HR 11.1; 95% CI, 4.45-27.46). When the multivariable model with H. pylori antibody was changed into that with the combination of H. pylori antibody and sPG, the C statistics for developing gastric cancer increased significantly (0.773 vs 0.732, P = 0.005), and the continuous net reclassification improvement value was 0.591 (P < 0.001).ConclusionsOur findings suggest that the combination of H. pylori antibody and sPG is a useful tool for predicting the development of gastric cancer.
| S-EPMC5121431 | biostudies-literature