B12 deficiency-related glossitis is highly associated with high gastrin-17 and low pepsinogen I.

BACKGROUND: The causes of vitamin B12 (B12) deficiency are varied and mainly related to gastric disorders. Glossitis is a common oral manifestation of B12 deficiency and is often first seen by dentists. This study aimed to investigate the correlation between B12 deficiency-related glossitis (B12-def glossitis) and gastric serum biomarkers [gastrin-17(G17), pepsinogen I (PGI), pepsinogen II (PGII), and anti-Helicobacter pylori (H. pylori) antibodies], and preliminarily discuss the etiology of B12-def glossitis. METHODS: A cross-sectional study was conducted in patients complaining of glossodynia, burning sensation, or severe recurrent oral ulcers, but patients with a history of gastrectomy were excluded. All subjects underwent a uniform oral examination and hematological tests. RESULTS: Of 243 patients, 133 with B12-def glossitis were in the case group, and 110 with other oral mucosal diseases (non-glossitis) and normal B12 levels were in the control group. In the case group, 84.2% (112/133) showed high G17 and low PGI levels (G17hi PGIlow ). Univariate logistic regression showed that G17hi PGIlow was a high-risk factor for B12-def glossitis (OR: 92.44; 95% CI: 35.91, 238.02). Subgroup analyses in the case group showed that the G17hi PGIlow group presented with lower B12 levels and a lower positive rate of anti-H. pylori antibodies compared to the non-G17hi PGIlow group. CONCLUSION: Gastric serum biomarkers in patients with B12-def glossitis generally showed G17hi PGIlow , suggesting possible atrophy of gastric corpus and fundus mucosa. The G17hi PGIlow and non-G17hi PGIlow groups may represent different etiologies of B12 deficiency.

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.

Pepsinogen ratio and brachial-ankle pulse wave velocity: a cross-sectional study on their interrelationship in atherosclerosis.

BACKGROUND: Existing research has established the pepsinogen ratio (PGR) as a complex biomarker, not only as an independent predictor for various gastrointestinal diseases but also in its association with atherosclerotic cardiovascular diseases. However, the precise mechanism linking changes in PGR to cardiovascular pathologies remains unclear. The objective of this study is to quantitatively elucidate the association between PGR and brachial-ankle pulse wave velocity (baPWV) as an indicator of atherosclerotic progression. METHODS: We conducted a cross-sectional study that analyzed clinical data from 465 patients who underwent health screenings. One-way Analysis of Variance (ANOVA) identified potential risk factors affecting baPWV. Multiple logistic regression was employed to evaluate if PGR serves as an independent risk factor for elevated baPWV after accounting for these variables. Generalized additive models and smoothed curve fitting were utilized to investigate the possibility of a nonlinear association between PGR and baPWV. When such nonlinearity was found, threshold effect analysis pinpointed the inflection point in this relationship, followed by segmented correlation analyses. RESULTS: PGR negatively correlated with both right baPWV (RbaPWV) and left baPWV (LbaPWV) after adjusting for confounders. Smoothed curve analyses revealed nonlinear relationships, with inflection points at 22.5 for RbaPWV and 22.3 for LbaPWV. For PGR values below 22.5, a significant negative correlation with RbaPWV was observed (ß = - 6.3 cm/s, P < 0.001). Conversely, for PGR values above 22.5, no significant linear relationship was found (P = 0.141). Similarly, when PGR was below 22.3, a strong negative correlation with LbaPWV was detected (ß = - 7.0 cm/s, P < 0.001), but such correlation was absent for higher PGR levels (P = 0.273). CONCLUSION: The study reveals that PGR is associated with RbaPWV and LbaPWV in a nonlinear manner. Specifically, lower levels of PGR were linearly and inversely correlated with baPWV, but this relationship became nonlinear at higher PGR levels. These findings suggest that modulating PGR levels may offer a therapeutic strategy for managing atherosclerosis.

Usefulness of Serum Pepsinogen I as a Biomarker in Early Diagnosis of Aetiology of Dyspepsia.

BACKGROUND: Dyspepsia, according to Rome III criteria, is defined as pain or discomfort centred in the upper abdomen in addition to symptoms like early satiety, postprandial fullness, bloating and nausea. Pepsinogens which are secreted by chief cells of the stomach play an important role in its physiology. They could determine the functional state of the mucosa in health and in diseased conditions. Serum levels of pepsinogen have aided the diagnosis of gastric pathologies such as atrophic gastritis, peptic ulcer disease and gastric cancer. Pepsinogen assay, being a simple, non-invasive procedure, can aid in determining the aetiology of dyspepsia especially in a resource poor setting. OBJECTIVE: This was to evaluate the diagnostic significance of serum pepsinogen I in patients with dyspepsia. METHODS: The study involved 112 adult patients with dyspepsia and an equal number of controls. A questionnaire was used to obtain biodata, clinical features and other relevant information. The patients had abdominal ultrasound scan, urea breath test and upper gastrointestinal endoscopy (UGIE), while the controls had only abdominal ultrasound scan. Sera prepared from 10ml of venous blood from each participant were stored at -20ºC and later analysed for pepsinogen I (PG I). RESULTS: Females predominated in both groups (F:M = 1.4:1). The mean age of cases was 51±15.9 years and was similar to that of controls 51.4±16.5. The most frequent symptom was epigastric pain in 101 (90.2%) patients. Median pepsinogen I level in patients (28.5ng/ml) was significantly lower than in controls (68.8ng/ml) (p<0.001). The most frequent endoscopic finding was gastritis. Serum PG I level at a cut-off point of 79.5ng/ml had a specificity of 88.8% and sensitivity of 40% in identifying dysplasia. CONCLUSION: Serum PG I level was lower in patients with dyspepsia than controls. It showed high specificity in identifying dysplasia and could be a biomarker for early gastric cancer.

CONTEXTE: La dyspepsie, selon les critères de Rome III, est définie comme une douleur ou une gêne centrée sur la partie supérieure de l'abdomen, en plus de symptômes tels qu'une satiété précoce, une plénitude postprandiale, des ballonnements et des nausées. Les pepsinogènes, sécrétés par les cellules principales de l'estomac, jouent un rôle important dans sa physiologie. Ils peuvent déterminer l'état fonctionnel de la muqueuse, qu'elle soit saine ou malade. Les taux sériques de pepsinogène ont facilité le diagnostic de pathologies gastriques telles que la gastrite atrophique, l'ulcère gastroduodénal et le cancer gastrique. Le dosage du pepsinogène, qui est une procédure simple et non invasive, peut aider à déterminer l'étiologie de la dyspepsie, en particulier dans un contexte de ressources limitées. OBJECTIF: Évaluer l'importance diagnostique du pepsinogène I sérique chez les patients souffrant de dyspepsie. MÉTHODES: L'étude a porté sur 112 patients adultes souffrant de dyspepsie : L'étude a porté sur 112 patients adultes souffrant de dyspepsie et un nombre égal de témoins. Un questionnaire a été utilisé pour obtenir les données biologiques, les caractéristiques cliniques et d'autres informations pertinentes. Les patients ont subi une échographie abdominale, un test respiratoire à l'urée et une endoscopie gastro-intestinale supérieure, tandis que les témoins n'ont subi qu'une échographie abdominale. Les sérums préparés à partir de 10 ml de sang veineux de chaque participant ont été conservés à -20ºC et analysés ultérieurement pour le pepsinogène I (PG I). RÉSULTATS: Les femmes prédominaient dans les deux groupes (F:M = 1,4:1). L'âge moyen des cas était de 51±15.9 ans et était similaire à celui des témoins 51.4±16.5. Le symptôme le plus fréquent était la douleur épigastrique chez 101 (90,2 %) patients. Le taux médian de pepsinogène I chez les patients (28,5 ng/ml) était significativement plus bas que chez les témoins (68,8 ng/ml) (p<0,001). Le résultat endoscopique le plus fréquent était la gastrite. Le taux sérique de PG I à un seuil de 79,5 ng/ml avait une spécificité de 88,8 % et une sensibilité de 40 % dans l'identification de la dysplasie. CONCLUSION: Le taux de PG I sérique était plus faible chez les patients souffrant de dyspepsie que chez les témoins. Il a montré une spécificité élevée dans l'identification de la dysplasie et pourrait être un biomarqueur pour le cancer gastrique précoce. Mots-clés: Dyspepsie, Pepsinogène I sérique, Helicobacter pylori, Biomarqueur.

A point-of-care chemiluminescence immunoassay for pepsinogen I enables large-scale community health screening.

Pepsinogen I (PGI) can reflect the morphology and function of the gastric mucosa. Accordingly, the large-scale community health screening of PGI can dramatically increase the early diagnosis rate of gastric cancer. However, PGI testing can only be carried out in comprehensive hospitals and health examination centers. To ameliorate this issue, a point-of-care chemiluminescent immunoassay for PGI was developed in a fully automated miniaturized instrument. This instrument was especially developed for health check-ups in the grassroots communities; its volume of which is only 0.18 m3. Critically, the entire detection process for a single sample only requires 20 min, and the samples can be loaded continuously, making the method suitable for high-throughput analysis. The assay displayed an excellent detection limit of 0.048 ng/mL with a broad detection range of 0-200 ng/mL. Furthermore, this assay exhibited high sensitivity and specificity, had low intra- and inter-assay coefficients of variation (<10%), and was not affected after storage at 37 °C for 7 days. The assay was used to detect PGI in 95 clinical serum samples, and the results were highly correlated with those that were clinically tested (correlation coefficient, R2 = 0.998). Hence, the method established in this work has great application value and can be broadly applied for the large-scale screening of gastric cancer in resource-limited areas.

Association between serum pepsinogen and atherosclerotic cardiovascular disease.

BACKGROUND AND AIM: Serum pepsinogens (PGs) are biomarkers for gastric mucosal damage and have been reported to be associated with atherosclerosis. Its correlation with atherosclerotic cardiovascular disease (ASCVD) is still unknown. This study aimed to explore the association between serum PGs and ASCVD for providing physicians with an integrative picture to make rational plans in the diagnosis and treatment of ASCVD. METHODS AND RESULTS: The concentrations of serum PGs and their distributions between ASCVD and non-ASCVD were compared by non-parametric test, Chi-squared test and Fisher exact test. The correlation between variables was analyzed by Spearman's correlation test. The association of serum PGs with ASCVD was analyzed by the binary logistic regression and two-piecewise linear regression. A total of 8355 recruited cases were eligible for the study. The concentrations of serum PGs were significantly different between the ASCVD and non-ASCVD groups (P = 0.025, P < 0.001). The lower PGI and PGR levels were significantly correlated with a high risk of ASCVD presence after adjustment for 26 potential covariates. Moreover, there was a linear relationship between the high level of PGII and the high risk of ASCVD [adjusted OR = 1.16 (1.00, 1.37), P = 0.07]. A nonlinear relationship of PGI/PGR and ASCVD (P = 0.08/<0.001) was also revealed. The risk of ASCVD increased with a range of log PGI ≥2.13 (PGI≥131 ng/mL) [adjusted OR = 4.67 (1.00, 23.17)], and decreased with a range of log PGR ≥0.22 (1.65) [adjusted OR = 0.59 (0.48, 0.74), P < 0.001]. CONCLUSIONS: Serum PGI and PGR are nonlinearly correlated with ASCVD, while PGII is linearly correlated with ASCVD. Among all PGs, PGR may serve as a reliable biomarker for ASCVD.

Microbiota changes with fermented kimchi contributed to either the amelioration or rejuvenation of Helicobacter pylori-associated chronic atrophic gastritis.

Korean fermented kimchi is probiotic food preventing Helicobacter pylori (H. pylori)-associated atrophic gastritis in both animal and human trial. In order to reveal the effect of fermented kimchi against H. pylori infection, we performed clinical trial to document the changes of fecal microbiota in 32 volunteers (H. pylori (-) chronic superficial gastritis (CSG), H. pylori (+) CSG, and H. pylori (+) chronic atrophic gastritis (CAG) with 10 weeks kimchi. Each amplicon is sequenced on MiSeq of Illumina and the sequence reads were clustered into operational taxonomic units using VSEARCH and the Chao, Simpson, and Shannon Indices. Though significant difference in α- or ß-diversity was not seen in three groups, kimchi intake led to significant diversity of fecal microbiome. As results, Klebsiella, Enterococcus, Ruminococcaceae, Streptococcus, Roseburia, and Clostirdiumsensu were significantly increased in H. pylori (+) CAG, while Akkermansia, Citrobacter, and Lactobacillus were significantly decreased in H. pylori (+) CAG. With 10 weeks of kimchi administration, Bifidobacterium, Lactobacillus, and Ruminococcus were significantly increased in H. pylori (+) CAG, whereas Bacteroides, Subdoligranulum, and Eubacterium coprostanolines were significantly decreased in H. pylori (-) CAG. 10 weeks of kimchi intake significantly improved pepsinogen I/II ratio (p<0.01) with significant decreases in interleukin-1ß. Conclusively, fermented kimchi significantly changed fecal microbiota to mitigate H. pylori-associated atrophic gastritis.

Simultaneous determination of gastric cancer biomarkers pepsinogen PGI/PGII using element tagged immunoassay coupled with inductively coupled plasma mass spectrometry detection.

OBJECTIVES: In this study, a new immunoassay for the simultaneous determination of pepsinogen I (PGI) and pepsinogen II (PGII) in serum based on element labeling strategy coupled with inductively coupled plasma mass spectrometry (ICP-MS) detection was proposed. METHODS: The sandwich-type immunoassay was used to simultaneously detect PGI and PGII in serum. PGI and PGII were captured by anti-PGI and anti-PGII antibody immobilized on the magnetic beads and then banded with Eu3+ labeled anti-PGI detection antibody and Sm3+ labeled anti-PGII detection antibody, followed by ICP-MS detection. RESULTS: The linear correlation coefficient (R2 ) of PGI and PGII standard curves was .9938 and .9911, with the dynamic range of 0-200 ng/mL and 0-60 ng/mL, respectively. The limit of detection for PGI and PGII was 1.8 ng/mL and 0.3 ng/mL, respectively. The average recovery was 101.41% ± 6.74% for PGI and 101.47% ± 4.20% for PGII. Good correlations were obtained between the proposed method and CLIA (r = .9588 for PGI, r = .9853 for PGII). CONCLUSIONS: We established a mass spectrometry-based immunoassay for the simultaneous detection of PGI and PGII in a single analysis. The element tagged immunoassay coupled with ICP-MS detection has high sensitivity, accuracy, and specificity in clinical serum sample analysis.

Gastroesophageal reflux symptoms and microscopic esophagitis in a cohort of consecutive patients affected by atrophic body gastritis: a pilot study.

AIM: In patients affected by atrophic body gastritis (ABG) gastro-oesophageal reflux (GER) related symptoms have been reported, despite the presence of hypochlorhydria. OBJECTIVE: Objectives of this single-centre study was to assess in ABG the occurrence of GER-related symptoms and their relationship with histopathologic oesophageal findings. MATERIALS AND METHODS: Fifty-four consecutive patients (20.4%male, 57.6 ± 14 years) undergoing to follow-up for ABG, underwent assessment of GER-related symptoms and gastroscopy with multiple gastric and oesophageal biopsies to investigate the presence of microscopic esophagitis (ME). RESULTS: At least one typical GER symptoms were reported in 24.1% with 9.2% of patients complaining of heartburn and 18.5% regurgitation. One or more atypical GERD symptoms were reported in 44.4% of patients. Two symptomatic ABG patients presented oesophageal lesions at endoscopy (one with erosive esophagitis (LA-C) and one with Barrett's oesophagus (C2M2)), 49% reported a mild ME and 24.5% a severe ME. No significant differences regarding GERD prevalence were found among patients with or without ME, but cough was the only symptom significantly more frequent in patients with ME (38.95% vs. 7.7%, p = .042). CONCLUSIONS: These data showed that GERD is present in a quarter of ABG patients, suggesting that hypochlorhydria not exclude per se arising of oesophageal symptoms. In ABG we found that ME is a frequent finding but its clinical relevance remains to be investigated with further studies.

Long-term gastric cancer risk in male smokers with atrophic corpus gastritis.

OBJECTIVES: The aim of this study was to evaluate long-term gastric cancer risk in male smokers with and without atrophic gastritis. MATERIALS AND METHODS: A total of 22,346 elderly male smokers participated in the Helsinki Gastritis Study between the years 1989 and 1993. Serum pepsinogen I (PGI) was measured for the men, and 2,132 men with low PGI (<25 µg/L; a marker of atrophic corpus gastritis) were invited to undergo gastroscopy because of increased gastric cancer risk. Endoscopy was performed to 1,327 men, who were followed up for a median of 13.6 years and a maximum of 25.3 years thereafter. In addition, the gastric cancer risk of men with low PGI was compared to that of the men with normal PGI and to the general Finnish male population of the same age. RESULTS: Thirty-five cases of gastric cancer were diagnosed in men with gastroscopy during the follow-up. The incidence rate was 1.94 per 1000 patient years. The men with a history of gastric surgery (n = 180) due to a benign cause had even higher gastric cancer incidence (3.2 per 1000 patient-years). Gastric cancer risk was highest in men with marked intestinal metaplasia in primary biopsies. Compared to the general Finnish male population of the same age, the cancer risk was 1.13 times higher in male smokers with normal serum PGI, and 2.43 times higher in men with low serum PGI. CONCLUSION: In male smokers, atrophic gastritis and intestinal metaplasia increase the risk of gastric cancer.

The applicability of ELISA detection of gastric mucosa-expressing proteins for the identification of vomit.

The identification of vomit stains may be helpful for crime scene reconstruction. However, there is no specific and convenient method for identifying vomit stain. Therefore, to establish the procedure for forensic identification of vomit stains, we focused on four gastric mucosa-expressing proteins, pepsinogen I (PGA), pepsinogen II (PGC), gastrin (GAST), and mucin 5AC (MUC5AC). We developed enzyme-linked immunosorbent assay (ELISA) procedures for the detection of these four candidate proteins. The specificity and sensitivity of ELISA detection of these proteins were analyzed, and applicability for the identification of vomit in forensic casework samples was also investigated. We found the sensitivities of ELISA for detection of PGA, PGC, GAST, and MUC5AC from the standard protein (peptide) and from diluted gastric mucosa extract were 10.0-100.0 ng/ml and 1:200-1:1600, respectively. PGA and PGC were successfully detected in stomach contents and gastric mucosa samples; however, these also cross-reacted with some urine and semen samples, respectively, because of low level expression in these fluids. MUC5AC was positive for most gastric mucosa samples; however, it was difficult to detect in stomach contents. ELISA detection of GAST was not suitable for the identification of vomit. All aged samples stored up to 90 days gave positive results for ELISA procedures for PGA, PGC, and MUC5AC. Therefore, ELISA detection of these proteins might be applicable to aged samples. PGA was also detected in all actual vomit samples tested. These results suggest that ELISA for the detection of gastric mucosa-expressing proteins, especially PGA, could be an effective tool for the forensic identification of vomit.

Evaluation of Pepsinogen I as a Biomarker of Drug-induced Gastric Mucosal Injury in Cynomolgus Monkeys.

Gastric mucosal injury is frequently observed in nonclinical studies of nonhuman primates. Because microscopic evaluation of stomach is generally a terminal procedure, our objective was to determine whether serum pepsinogen I (PG I) could serve as a noninvasive biomarker for detection of gastric mucosal injury in monkey. Serum PG I was measured using a commercial human immunoassay in cynomolgus monkeys ( n = 166) prior to dosing and/or terminally in 11 studies of up to 1 month duration. Mean ( SD) PG I values (ug/L) for monkeys with ( n = 59) and without ( n = 100) gastric mucosal degeneration were 101 (215) and 28 (12.6), respectively. For monkeys with baseline and terminal PG I data, mean ( SD) fold change (ratio of terminal to baseline PG I) for monkeys with ( n = 57) and without ( n = 76) glandular degeneration were 4.1 (11.3) and 1 (0.28). Receiver operating characteristic area under the curve (AUC) data demonstrated moderate diagnostic accuracy for serum PG I for glandular degeneration, AUC ( SE) 0.789 (0.04), with improved diagnostic accuracy as a fold change of baseline, AUC ( SE) 0.816 (0.04), consistent with the large interindividual but low intraindividual variability of serum PG I values in control monkeys. These data demonstrate that serum PG I is a useful biomarker of drug-induced gastric mucosal injury in the cynomolgus monkey.

A magnetic nanoparticle-labeled immunoassay with europium and samarium for simultaneous quantification of serum pepsinogen I and II.

OBJECTIVE: To develop a novel immunoassay for the simultaneous determination of serum pepsinogen I (PG I) and pepsinogen II (PG II) by combining established methods of time-resolved fluoroimmunoassay (TRFIA) and magnetic nanoparticles separation. MATERIALS AND METHODS: This new immunoassay method was characterised by immobilising primary antibodies on the surface of magnetic particles and labelled with stable fluorescent chelates of europium and samarium. RESULTS: Using magnetic nanoparticles, the TRFIA immunoassay exhibited broad dynamic assay ranges for PG I with detection limit of 0.33 ng/mL, while for PG II with detection limit of 0.38 ng/mL. Cross-reactivity between PGs I and II were <15. The intra- and inter-assay coefficient variations of the method were <3%, and the recoveries were in the range of 97-103% for serum samples. Bland-Altman analysis of 124 serum samples showed good consistency with a commercial TRFIA kit. For PG I, the mean (95% confidence interval) difference was 0.97 (-14.3-12.3) ng/mL, whilst for PG II the difference was 0.6 (-4.4-3.2) ng/mL. CONCLUSIONS: Our data suggest that the method is feasible and could be developed into a platform for the routine clinical determination of PG I and PG II levels in human serum.

Clinicopathological features of gastric adenocarcinoma of the fundic gland (chief cell predominant type) by retrospective and prospective analyses of endoscopic findings.

BACKGROUND AND AIM: Gastric adenocarcinoma of the fundic gland type (chief cell predominant type) (GA-FG-CCP) is a variant of gastric adenocarcinoma with chief cell differentiation. GA-FG-CCP is rare and not well understood. The present study aimed to investigate the clinicopathological features of GA-FG-CCP using retrospective and prospective analyses of endoscopic findings. METHODS: A total of 20 patients including nine cases treated with endoscopic submucosal dissection (ESD) were diagnosed with GA-FG-CCP. Morphological changes were analyzed by retrospectively retracing past endoscopic records and following up after definitive diagnoses, including the status of Helicobacter pylori (H. pylori) infection. RESULTS: GA-FG-CCP were small and whitish lesions accompanied by atypical vascular growth and their macroscopic types were classified as 0-IIa (60%), 0-IIb (25%), and 0-IIc (15%), respectively. The lesions were found in the non-atrophic gastric mucosa of the upper (70%) or middle portion (30%), although gastric mucosal atrophy associated with current or past H. pylori infection was identified in 75% of cases. In the nine cases treated with ESD, submucosal invasion was identified in 80% of the resected lesions, but no lymphovenous infiltration was detected. Ki-67 labeling index of GA-FG-CCP was low at 3.2% and visible morphological changes were rarely detected during long-term endoscopic observation for 58.9 ± 13.1 months. CONCLUSIONS: These data indicate that GA-FG-CCP, even when submucosal invasion occurs easily, might be of low-grade malignancy as long as it is the chief cell predominant type without other epithelial abnormalities. In addition, GA-FG-CCP might develop despite H. pylori infection or gastric mucosal atrophy.

Redox probe-free electrochemical immunosensor utilizing electropolymerized melamine on reduced graphene oxide for the point-of-care diagnosis of gastric cancer.

Pepsinogen I (PG I) is a biomarker that plays a crucial role in the diagnosis of gastric cancer. The development of biosensor to monitor PG I overexpression in serum is crucial for early gastric cancer diagnosis, offering a less invasive alternative to the costly and uncomfortable gastroscopy procedure. This study presents a cost-efficient, scalable and disposable label-free biosensing strategy for detecting PG I, utilizing a redox-active polymelamine electrodeposited on a reduced graphene oxide screen-printed electrode surface (PM-rGO/SPE). Under optimized conditions, the conducting polymer PM was deposited on the rGO/SPE via a potentiodynamic method. The structural and morphological features of PM-rGO/SPE were analyzed with the assistance of Raman and Scanning Electron Microscopy analysis. Specific monoclonal anti-PG I antibodies were immobilized on the in situ prepared redox-active layer via EDC/NHS chemistry to develop a novel electrochemical immunosensor. Unlike the traditional immunosensing strategies which utilizes external redox probe solution for measuring the signal, the developed configuration allowed for redox-probe free monitoring of current changes of the redox active PM resulting from the formation of the immunocomplex on the electrode surface. Utilizing this method, PG I detection spanned a clinically relevant concentration range of 0.01-200 ng/mL, with a low limit of detection at 9.1 pg/mL. The electrochemical immunosensor demonstrated specificity against other biomarkers such as PDCD1, ErBb2, and CD28 with negligible interference. The immunosensor exhibited excellent recovery capabilities for PG I detection in serum samples. These findings underscore the potential of the PM-rGO/SPE immunosensor as a point-of-care diagnostic tool for gastric cancer.

The role of gastrin 17 and pepsinogen I:pepsinogen II ratio in pathological diagnosis and endoscopic selection in gastritis patients.

BACKGROUND: The noninvasive serum markers pepsinogen I (PGI), pepsinogen II (PGII), gastrin-17 (G17), and PGI:PGII ratio (PGR) have recently been proposed as a new tool for predicting various gastric pathologies. METHODS: A total of 83 gastritis patients confirmed by gastroscopy were enrolled, with 78 undergoing concurrent colonoscopies. The control group included 99 healthy subjects. Enzyme-linked immunosorbent assay was used to detect PGI, PGII, G17, and PGR. The performance of serological analysis for detecting gastritis pathology was evaluated using receiver operating characteristic (ROC) curves. RESULTS: The G17 and PGII levels increased significantly (P < .001), whereas PGR levels decreased (P = .001) in the gastritis group. The ROC analysis revealed that PGR had a sensitivity and specificity of 70.83% and 86.67%, respectively, in predicting Helicobacter pylori-infected gastritis and a sensitivity and specificity of 88% and 65.52%, respectively, in predicting active gastritis. The G17 levels were significantly elevated in gastritis patients undergoing concurrent colonoscopies (P < .05). CONCLUSION: Pepsinogen I:pepsinogen II ratio was found to be a useful predictor of active gastritis and H pylori-infected gastritis. Furthermore, G17 was found to be closely related to pathological conditions found by colonoscopy and may provide recommendations for whether gastritis patients should undergo a concurrent colonoscopy.

Influence of a diet meal plan on pepsinogen I and II, gastrin-17, and nutritional status in gastric ulcer patients.

BACKGROUND: Gastric ulcers (GUs) have a high risk of clinical morbidity and recurrence, and further exploration is needed for the prevention, diagnosis, and treatment of the disease. AIM: To investigated the effects of a diet plan on pepsinogen (PG) I, PG II, gastrin-17 (G-17) levels and nutritional status in patients with GUs. METHODS: A total of 100 patients with GUs treated between May 2022 and May 2023 were enrolled, with 47 patients in the control group receiving routine nursing and 53 patients in the experimental group receiving dietary nursing intervention based on a diet plan. The study compared the two groups in terms of nursing efficacy, adverse events (vomiting, acid reflux, and celialgia), time to symptom improvement (burning sensation, acid reflux, and celialgia), gastric function (PG I, PG II, and G-17 levels), and nutritional status [prealbumin (PA) and albumin (ALB) levels]. RESULTS: The experimental group showed a markedly higher total effective rate of nursing, a significantly lower incidence of adverse events, and a shorter time to symptom improvement than the control group. Additionally, the experimental group's post-intervention PG I, PG II, and G-17 levels were significantly lower than pre-intervention or control group levels, whereas PA and ALB levels were significantly higher. CONCLUSION: The diet plan significantly reduced PG I, PG II, and G-17 levels in patients with GUs and significantly improved their nutritional status.

A feasibility study on utilizing machine learning technology to reduce the costs of gastric cancer screening in Taizhou, China.

Aim: To optimize gastric cancer screening score and reduce screening costs using machine learning models. Methods: This study included 228,634 patients from the Taizhou Gastric Cancer Screening Program. We used three machine learning models to optimize Li's gastric cancer screening score: Gradient Boosting Machine (GBM), Distributed Random Forest (DRF), and Deep Learning (DL). The performance of the binary classification models was evaluated using the area under the curve (AUC) and area under the precision-recall curve (AUCPR). Results: In the binary classification model used to distinguish low-risk and moderate- to high-risk patients, the AUC in the GBM, DRF, and DL full models were 0.9994, 0.9982, and 0.9974, respectively, and the AUCPR was 0.9982, 0.9949, and 0.9918, respectively. Excluding Helicobacter pylori IgG antibody, pepsinogen I, and pepsinogen II, the AUC in the GBM, DRF, and DL models were 0.9932, 0.9879, and 0.9900, respectively, and the AUCPR was 0.9835, 0.9716, and 0.9752, respectively. Remodel after removing variables IgG, PGI, PGII, and G-17, the AUC in GBM, DRF, and DL was 0.8524, 0.8482, 0.8477, and AUCPR was 0.6068, 0.6008, and 0.5890, respectively. When constructing a tri-classification model, we discovered that none of the three machine learning models could effectively distinguish between patients at intermediate and high risk for gastric cancer (F1 scores in the GBM model for the low, medium and high risk: 0.9750, 0.9193, 0.5334, respectively; F1 scores in the DRF model for low, medium, and high risks: 0.9888, 0.9479, 0.6694, respectively; F1 scores in the DL model for low, medium, and high risks: 0.9812, 0.9216, 0.6394, respectively). Conclusion: We concluded that gastric cancer screening indicators could be optimized when distinguishing low-risk and moderate to high-risk populations, and detecting gastrin-17 alone can achieve a good discriminative effect, thus saving huge expenditures.

Serum gastrin 17, pepsinogen I and pepsinogen II in atrophic gastritis patients living in North-East of Iran.

BACKGROUND: Gastric carcinoma is the second most common cause of cancer-related death in Iran. It is well-known that atrophic gastritis is a major risk factor for gastric cancer, which leads to variations in the serum levels of gastrin 17 (G-17), pepsinogen I (P-I), and pepsinogen II (P-II). The aim of this study was to investigate the diagnostic accuracy of these serum biomarkers in the early detection of atrophic gastritis. MATERIALS AND METHODS: A total of 132 dyspeptic patients underwent upper endoscopy and biopsies were taken. The biopsy specimens were evaluated as the gold standard according to operative link for gastritis assessment staging system. Serum levels of G-17, P-I, and P-II were investigated using enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) analysis was used to calculate the diagnostic indices and optimal cut-off values using Statistical Package for the Social Sciences SPSS statistical software. RESULTS: A total of 67 men and 65 women were analyzed, among which 48 (36.4%) had atrophic gastritis. The mean age was 45.8 (±15.8) years. ROC curve analysis demonstrated that the biomarkers (including pepsinogen I/II [P-I/II] ratio), except for P-I, are diagnostically significant in detecting gastric atrophy. The area under the curve (95% confidence interval [CI]) for G-17, P-I, P-II, and P-I/II ratio were 0.65 (0.55-0.76), 0.42 (0.32-0.53), 0.62 (0.52-0.72), and 0.61 (0.50-0.72), respectively. However, the diagnostic indices were low (sensitivity <50%, specificity < 90%). The prevalence of Helicobacter pylori infection was significantly higher in patients with atrophy against those without atrophy (75.0% vs. 57.4%, P value < 0.0001). CONCLUSION: In the studied population, the serum biomarkers of atrophic gastritis are not useful screening tests due to their low sensitivity.

Value of Serological Biomarker Panel in Diagnosis of Atrophic Gastritis and Helicobacter pylori Infection.

Background: Gastric cancer is one of the most common types of cancer worldwide. Helicobacter pylori infection is clearly correlated with gastric carcinogenesis. Therefore, the use of a new non-invasive test, known as the GastroPanel test, can be very helpful to identify patients at a high risk, including those with atrophic gastritis, intestinal metaplasia, and dysplasia. This study aimed to compare the results of GastroPanel test with the pathological findings of patients with gastric atrophy to find a safe and simple alternative for endoscopy and biopsy as invasive methods. Methods: This cross-sectional study was performed on patients with indigestion, who were referred to Motahari Clinic and Shahid Faghihi Hospital of Shiraz, Iran, since April 2017 until August 2017 for endoscopy of the upper gastrointestinal tract. The serum levels of gastrin-17 (G17), pepsinogen I (PGI), and pepsinogen II (PGII), as well as H. pylori antibody IgG, were determined by ELISA assays. Two biopsy specimens from the antrum and gastric body were taken for standard histological analyses and rapid urease test. A pathologist examined the biopsy specimens of patients blindly. Results: A total of 153 patients with indigestion (62.7% female; mean age, 63.7 years; 37.3% male; mean age, 64.9 years) were included in this study. The G17 levels significantly increased in patients with chronic atrophic gastritis (CAG) of the body (9.7 vs. 32.8 pmol/L; P = 0.04) and reduced in patients with antral CAG (1.8 vs. 29.1 pmol/L; P = 0.01). The results were acceptable for all three types of CAG, including the antral, body, and multifocal CAG (AUCs of 97%, 91%, and 88% for body, antral, and multifocal CAG, respectively). The difference in PGII level was not significant. Also, the PGI and PGI/PGII ratio did not show a significant difference (unacceptably low AUCs for all). The H. pylori antibody levels were higher in patients infected with H. pylori (251 EIU vs. 109 EIU, AUC = 70, P = 0.01). There was a significant relationship between antibody tests and histopathology. Conclusion: Contrary to Biohit's claims, the GastroPanel kit is not accurate enough to detect CAG; therefore, it cannot be used for establishing a clinical diagnosis.