Pepsinogen Research Articles

Incidence of Infection among Subjects with Helicobacter pylori Seroconversion.

Background/Aims:Helicobacter pylori (H. pylori) seroconversion may occur during screening for gastric cancer. Our study aimed to assess the number of seroconverted subjects with H. pylori and their results in follow-up tests. Methods:Data were consecutively collected on subjects who were H. pylori-seronegative and presented for gastric cancer screening. Subjects who were followed up using the same serology test and pepsinogen (PG) assays on the day of endoscopy were included in the study. Results:During the follow-up of 57.7±21.4 months, 61 (15.0%) of 407 seronegative subjects showed seroconversion. H. pylori infection was detected in six (9.8%) of 61 seroconverted subjects. A diffuse red fundal appearance, with a significant increase in the Kyoto classification scores for gastritis, was observed in the infected subjects (p<0.001). Compared to the false-seropositive subjects, infected subjects showed higher serology titers (p<0.001) and PG II levels (p<0.001) and lower PG I/II ratios (p=0.002), in the follow-up tests. Conclusions:Seroconversion occurred in 3.3% of seronegative subjects per year; however, only 9.8% had H. pylori infection. The majority (90.2%) of the seroconverted subjects showed false seropositivity without significant changes in the follow-up test results. The diffuse red fundal appearance could be an indicator of H. pylori infection.

High Prevalence of Helicobacter pylori Infection, Atrophic Gastritis and Hypochlorhydria in HIV-Positive Cameroonians Tested by Serological Stomach-Specific Biomarkers (GastroPanel®)

Background: The human immunodeficiency virus (HIV) and Helicobacter pylori (H. pylori) are associated with significant chronic inflammation of the gastric mucosa. Gastric inflammation is a precursor to many gastrointestinal disorders including, peptic ulcer disease, atrophic gastritis (AG) and gastric cancer (GC). AG is usually accompanied by low hydrochloric acid (hypochlorhydria), low pepsinogens (PG) and high gastrin (G) levels and is the most significant risk condition for GC. Acid-free stomach is a risk factor for impaired drug absorption including anti-retroviral therapy and antibiotics. The role of H. pylori infection in HIV-infected subjects has been conflicting.&#x0D; Objectives: We assessed the prevalence of H. pylori infection, AG and acid-free stomach (hypochlorhydria) amongst HIV/AIDS subjects in Yaounde Cameroon.&#x0D; Methods: HIV/AIDS subjects were recruited during January-May 2018. Clinical and socio-demographic data of the subjects were recorded. An aliquot of 5 ml of blood was aseptically collected for analysis by GastroPanel® biomarker test for PGI, PGII, G-17 and H.pylori IgG antibodies. GastroPanel results were interpreted using the software application GastroSoft®. Statistical analyses were run by Epiinfo7.0. Ethical clearance was obtained from the National Ethics Committee.&#x0D; Results: A total of 84 subjects were recruited, aged between 17-63 years (mean 37.6 ± 8.9 years). H. pylori seropositivity (IgG ≥30 EIU) was detected in 68(81.0%) of the subjects. H. pylori seropositivity was closely associated with low CD4 counts (p=0.01). Altogether, 26(31.0%) of the subjects presented with AG of the corpus while, hypochlorhydria was detected in 32(38.1%) of the patients. AG and hypochlorhydria were associated with low CD4 counts&lt;200μl/l (p=0.01) and (p=0.005), respectively.&#x0D; Conclusion: H. pylori infection, AG and acid-free stomach were common among HIV/AIDS patients, associated with an increased risk for GC and impaired absorption of micronutrients and some medicines.

HELICOBACTER PYLORI CHRONIC GASTRITIS ON PATIENTS WITH PREMALIGNANT CONDITIONS: OLGA AND OLGIM EVALUATION AND SERUM BIOMARKERS PERFORMANCE.

H. pylori chronic atrophic gastritis is a premalignant lesion, and its staging, according to OLGA and OLGIM systems aims to identify patients at increased risk of developing gastric cancer and optimize their follow-up. GastroPanel®, serum biomarkers panel including pepsinogen I (PGI), pepsinogen II (PGII), Gastrin 17 (G17) and anti- H. pylori antibodies is a noninvasive test for adenocarcinoma risk assessment in chronic H. pylori gastritis patients. Prospective study to evaluate the concordance between OLGA and OLGIM grading systems, as well as to evaluate GastroPanel´s performance in patients with premalignant lesions secondary to H. pylori chronic gastritis in Brazil. Patients with H. pylori chronic gastritis with premalignant lesions confirmed by histology were recruited from the gastrointestinal clinic of a University Hospital. All participants underwent endoscopic examination with biopsies which were reported according to updated Sydney system and premalignant lesions grading systems (OLGA and OLGIM). Blood samples were collected for biomarkers serological analysis (GastroPanel®, Biohit, Helsinki, Finland). The cut off values used to define high risk patients were those recommended by the manufacturer: PGI ≤30 µm/L and PGI/PGII ≤3. 41 patients were recruited: 28 women, 13 men, mean age 67.3 (47-89, SD: 9.6) years. By OLGA system, were obtained: OLGA 0 (n=1), OLGA I (n=7), OLGA II (n=17), OLGA III (n=9), and OLGA IV (n=7). By OLGIM system, were obtained: OLGIM 0 (n=14), OLGIM I (n=5), OLGIM II (n=10), OLGIM III (n=10), and OLGIM IV (n=2). Regarding histological staging among patients staged as low risk (OLGA/OLGIM 0, I and II) and high risk (OLGA/OLGIM III and IV) for gastric cancer development, the concordance rate found between both classifications was 85.4%. Considering high risk patients, those patients thus included in at least one of the systems the final distribution of our sample considered 24 low-risk and 17 high-risk patients for the development of gastric cancer. To determine by GastroPanel® whether the patient would be at low or high risk of developing gastric cancer, PGI showed a sensitivity, specificity and accuracy of 0.47 (95%CI: 0.26-0.69), 0.67 (95%CI: 0.47-0.82), and 0.58 (95%CI: 0.43-0.72), respectively, while PGI/PGII showed sensitivity, specificity and accuracy of 0.06 (95%CI: 0.01-0.27), 0.83 (95%CI: 0.64-0.93) and 0.51 (95%CI: 0.36-0.66), respectively. The histological classifications OLGA and OLGIM presented a substantial concordance rate among themselves. Simultaneous use of both histological classification systems increased the identification's rate of high-risk patients. Biomarker analysis was not effective to distinguish low to high risk patients in the studied population. Further studies are needed to validate its use in clinical practice in Brazil.

A comparative study of new gastric cancer screening scoring system and new ABC method for screening gastric cancer and precancerous lesions

Objective: To compare the value of new gastric cancer screening scoring system and serum pepsinogen (PG) combined with gastrin-17 (G-17) (new ABC method) in screening gastric cancer and precancerous lesions. Methods: A total of 576 patients were enrolled after the examination of endoscopy at Endoscopy Center,Department of Gastroenterology,from December 2017 to December 2019. There were 275 males and 301 females with an age of 40-72 (52±10) years. According to the new ABC method and the new gastric cancer screening scoring system, the population was divided into three groups according to age,gender,serum helicobacter pylori antibody test, PG Ⅰ/PG Ⅱ(PGR) and G-17 before endoscopy. The detection rates of gastric cancer and atrophic gastritis by two different methods were analyzed and the value in screening gastric cancer and precancerous lesions were evaluated. Statistical analysis was accomplished by Chi-square test and Gamma coefficient analysis. Results: A total of 576 patients were enrolled. According to the new ABC method, 382 patients were classified into low-risk group, 170 patients into middle-risk group and 24 patients into high-risk group, respectively. In the new ABC method, 1 case of gastric cancer (0.3%) was detected in low-risk group, 8 cases (4.7%) in middle-risk group and 3 cases (12.5%) in high-risk group. As for atrophic gastritis, 89 cases (23.3%) was detected in low-risk group, 94 cases (55.3%) in middle-risk group and 18 cases (75.0%) in high-risk group. According to the new gastric cancer screening scoring system, 336 patients were classified into low-risk group, 205 patients into middle-risk group and 35 patients into high-risk group, respectively. One case of gastric cancer (0.3%) was detected in low-risk group, 6 cases (2.9%) in middle-risk group and 5 cases (14.3%) in high-risk group. As for atrophic gastritis, 41 cases (12.2%) were detected in low-risk group, 134 cases (65.4%) in middle-risk group and 26 cases (74.3%) in high-risk group. In this two methods, the prevalence of gastric cancer increased according to the disease stage (χ²=22.509, P<0.01; χ²=24.156, P<0.01); in terms of atrophic gastritis, the detection rate of the new screening scoring system in the low-risk group was significantly lower than that in the new ABC method (χ²=14.844, P<0.01), but higher in the middle-risk group (χ2=3.955, P=0.047). Gamma coefficient test showed that there were strong correlations between gastroscopy pathology and classification grade of both methods (P<0.01). Conclusions: Both methods are suitable for screening gastric cancer and precancerous lesions, and the new scoring system may be more valuable in screening gastric cancer and precancerous lesions.

Factors associated with the progression of gastric intestinal metaplasia: a multicenter, prospective cohort study.

Background and study aims Gastric cancer (GC) is usually preceded by premalignant gastric lesions (GPLs) such as gastric intestinal metaplasia (GIM). Information on risk factors associated with neoplastic progression of GIM are scarce. This study aimed to identify predictors for progression of GIM in areas with low GC incidence. Patients and methods The Progression and Regression of Precancerous Gastric Lesions (PROREGAL) study includes patients with GPL. Patients underwent at least two upper endoscopies with random biopsy sampling. Progression of GIM means an increase in severity according to OLGIM (operative link on gastric intestinal metaplasia) during follow-up (FU). Family history and lifestyle factors were determined through questionnaires. Serum Helicobacter pylori infection, pepsinogens (PG), gastrin-17 and GC-associated single nucleotide polymorphisms (SNPs) were determined. Cox regression was performed for risk analysis and a chi-squared test for analysis of single nucleotide polymorphisms. Results Three hundred and eight patients (median age at inclusion 61 years, interquartile range (IQR: 17; male 48.4 %; median FU 48 months, IQR: 24) were included. During FU, 116 patients (37.7 %) showed progression of IM and six patients (1.9 %) developed high-grade dysplasia or GC. The minor allele (C) on TLR4 (rs11536889) was inversely associated with progression of GIM (OR 0.6; 95 %CI 0.4–1.0). Family history (HR 1.5; 95 %CI 0.9–2.4) and smoking (HR 1.6; 95 %CI 0.9–2.7) showed trends towards progression of GIM. Alcohol use, body mass index, history of H. pylori infection, and serological markers were not associated with progression. Conclusions Family history and smoking appear to be related to an increased risk of GIM progression in low GC incidence countries. TLR4 (rs11536889) showed a significant inverse association, suggesting that genetic information may play a role in GIM progression.

Significance of pepsinogen in screening for gastric intestinal metaplasia in Guangdong, China.

ObjectiveDiagnosis of gastric intestinal metaplasia (GIM) relies on gastroscopy and histopathologic biopsy, but their application in screening for GIM is limited. We aimed to identify serological biomarkers of GIM via screening in Guangdong, China.MethodsCross-sectional field and questionnaire data, demographic information, past medical history, and other relevant data were collected. Blood samples were collected for pepsinogen (PG)I, PGII, gastrin-17, and Helicobacter pylori antibody testing, and gastroscopy and histopathologic biopsy were performed. Single factor and logistic regression analyses were used to evaluate the correlation between these indicators and GIM, and decision tree models were used to determine the cut-off points between indicators.ResultsOf 443 participants enrolled, 87 (19.6%) were diagnosed with GIM. Single factor analysis showed that pepsin indicators (PGI, PGII, and PGI/PGII ratio) and the factors Mandarin as native language, urban residency, hyperlipidemia, and age were associated with GIM. Logistic regression analysis showed that PGI and age were associated with GIM.ConclusionsAge is an important factor for predicting GIM progression; age >60 years increased its risk. Detection of GIM was higher in individuals with PGI levels >127.20 ng/mL, which could be used as a threshold indicating the need to perform gastroscopy and histopathologic biopsy.

The TNF-A–857*T Polymorphism is Associated with Gastric Adenocarcinoma Risk in a Costa Rican Population

BackgroundCosta Rica is ranked as one of the countries with highest incidence of gastric cancer worldwide. Previous studies in Costa Rican populations have revealed associations between gastric cancer risk and several cytokine polymorphisms that seem to play a role in the regulation of the expression of these proteins. In this study, we assessed associations of the polymorphisms IL-6-174 G/C, IFNGR1-56 C/T, IL-8-251 T/A and TNF-A (-857 C/T, -308 A/G) with gastric pathologies in a high-risk population of Latin America. MethodsDNA samples of 47 patients with gastric adenocarcinoma, 53 with chronic gastritis, 56 with duodenal ulcer and 94 healthy controls, were genotyped for the five mentioned SNPs. All participants were ≥50-years-old. Genotyping was performed by PCR-RFLP and 5’-nuclease PCR assay. H. pylori infection, CagA status, pepsinogen (PG) I and II blood levels were determined by ELISA. Logistic regression analysis was used to determine possible associations of the polymorphisms with cancer, gastritis and duodenal ulcer, and linear regression analysis to determine associations with blood PG levels. ResultsA total of 86.6% of the population was positive for H. pylori; of them, 51.6% was CagA+. Patients with the TNF-A-857*T allele had an increased risk for gastritis (OR: 3.67, p = 0.015) and gastric adenocarcinoma (OR:6.15, p = 0.001). Associations between other polymorphisms and gastric diseases, or PG levels, were not found. ConclusionsOur results indicate that the TNF-A-857*T SNP is among the risk factors associated with the risk of gastric cancer in Costa Rica.

Pyloric, pseudopyloric, and spasmolytic polypeptide-expressing metaplasias in autoimmune gastritis: a case series of 22 Japanese patients

There are two types of pyloric gland-like metaplasia in the corpus of stomach: pyloric and pseudopyloric metaplasias. They show the same morphology as the original pyloric glands in H&E staining. Pseudopyloric metaplasia is positive for pepsinogen (PG) I immunohistochemically, whereas pyloric metaplasia is negative. Recently, spasmolytic polypeptide-expressing metaplasia (SPEM) is proposed for pyloric gland-like metaplasia mainly in animal experiments. SPEM expresses trefoil factor family 2 (TFF2) and is often considered synonymous with pseudopyloric metaplasia. We reviewed consecutive 22 Japanese patients with autoimmune gastritis (AIG) to investigate TFF2 expression in pyloric and pseudopyloric metaplasias by counting all pyloric gland-like glands in biopsy specimens taken from greater curvature of the middle corpus according to the Updated Sydney System. Pyloric metaplasia was seen in all the 22 cases, and pseudopyloric metaplasia was found in 15 cases. Of 1567 pyloric gland-like glands in all the cases, 1381 (88.1%) glands were pyloric metaplasia glands, and the remaining 186 (11.9%) glands were pseudopyloric metaplasia glands. TFF2 expression was observed in pyloric or pseudopyloric metaplasia glands in 20 cases. TFF2 expression was recognized in 409 of 1381 (26.9%) pyloric metaplasia glands and 27 of 186 (14.5%) pseudopyloric metaplasia glands (P<0.01, chi-square test). In conclusion, SPEM was not always the same as pseudopyloric metaplasia in human AIG, and the majority of metaplasia in AIG was not pseudopyloric but pyloric metaplasia.

Serum pepsinogen as a biomarker for gastric cancer: A nested case-control study using the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial data.

188 Background: Gastric cancer (GC) lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, which is an intermittent phase in the development of GC. A serum based biomarker that indicates increased risk of GC would be useful for targeted prevention strategies. Methods: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a large randomized trial conducted over 10 centers in the US between 1993 and 2001. Serum samples were collected at baseline and participants were followed for development of incident GC. ELISA-based pepsinogen tests were conducted on pre-diagnostic serum samples of patients who developed GC and age, sex, and race-matched controls. Pepsinogen negative (PG-) and positive (PG+) status was determined using pepsinogen I (PGI) and pepsinogen I to II ratio (PGR). Those with PGR ≥ 3 and PGI &gt; 70µg/L were considered PG- while those with lower levels on either or both were considered PG+. Cox proportional hazard models were used to determine the hazard ratio (HR) and 95% confidence intervals (95%CI) of PG+ for GC. To examine the association of PG with non-cardia and cardia GC separately, propensity matching was used to create control subsets matched on age, sex, and race. Results: Pepsinogen test results were available on 105 GC cases (70 non-cardia and 35 cardia) and 220 matched controls. Median and range of time from pepsinogen measurement to incident GC diagnosis was 78.6 and 3.0-152.2 months, respectively. GC patients were more likely to be PG+ (31.4% vs 5.5%, p &lt; 0.001) and current smokers (20.0% vs 7.7%, p = 0.004) at baseline than controls. Compared to PG-, PG+ were at an increased risk of any GC (HR = 3.77; 95%CI = 2.50-5.71). After adjusting for family history of GC, smoking, and BMI, PG+ were still at a significantly increased risk of GC compared to PG- (adjusted HR = 4.42; 95%CI = 3.14-6.21). For 138 controls matched to 70 non-cardia cancers, PG+ were at an increased risk of non-cardia GC compared to PG- (HR = 5.65, 95%CI = 3.67-8.70; adjusted HR = 7.26, 95%CI = 4.84-10.90). For 70 controls matched to 35 cardia cancers, PG+ were not at greater risk of cardia GC compared to PG- (HR = 1.79, 95%CI = 0.72-4.44; adjusted HR = 1.95, 95%CI = 0.81-5.37). Conclusions: Pre-diagnostic serum pepsinogen levels from a large prospective cohort study predicted development of non-cardia GC but not cardia GC. PG could be considered as a potential risk biomarker to identify individuals at higher risk of non-cardia GC for targeted screening or interventions.

Pepsinogens and Gastrin Demonstrate Low Discrimination for Gastric Precancerous Lesions in a Multi-Ethnic United States Cohort

Early identification of gastric precancerous lesions, including atrophic gastritis (AG) and intestinal metaplasia (IM), may improve gastric cancer detection and prevention. Because AG and IM are generally asymptomatic, many of the estimated 15 million Americans who carry these lesions remain undiagnosed.1 AG and IM are associated with either active or prior Helicobacter pylori (Hp) infection. Hp infection leads to perturbations in the serum concentration of gastric hormones pepsinogen I (PGI), pepsinogen II, the pepsinogen I/II ratio (PGR), gastrin-17 (G-17), and Hp IgG.2,3 In East Asia and other regions with high burden of Hp infection and gastric cancer, these biomarkers have been used as screening tools for AG and IM.4 However, there exists limited data on the sensitivity and discrimination of these serologic markers in low-Hp-prevalence populations, such as the United States.

Polymorphisms in Pepsinogen C and miRNA Genes Associate with High Serum Pepsinogen II in Gastric Cancer Patients

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Serum pepsinogen levels and OLGA/OLGIM staging in the assessment of atrophic gastritis types

BackgroundWe assessed the validity of using serum pepsinogen tests (sPGTs) to differentiate autoimmune atrophic gastritis (AAG) from environmental atrophic gastritis (EAG). We also investigated the correlation and prognostic value between...

High prevalence of Helicobacter pylori infection, atrophic gastritis and hypochlorhydria in HIV-positive Cameroonians

Background: The human immunodeficiency virus (HIV) and Helicobacter pylori (H. pylori) are associated with significant chronic inflammation of the gastric mucosa. Gastric inflammation is a precursor to many gastrointestinal disorders including, peptic ulcer disease, atrophic gastritis (AG) and gastric cancer (GC). AG is usually accompanied by low hydrochloric acid (hypochlorhydria), low pepsinogens (PG) and high gastrin (G) levels and is the most significant risk condition for GC. Acid-free stomach is a risk factor for impaired drug absorption including anti-retroviral therapy and antibiotics. The role of H. pylori infection in HIV-infected subjects has been conflicting. We assessed the prevalence of H. pylori infection, AG and acid-free stomach (hypochlorhydria) amongst HIV/AIDS subjects in Yaounde Cameroon. Methods and materials: A total of 84 HIV/AIDS subjects were recruited in Yaounde (Cameroon) during January-May 2018. Clinical and socio-demographic data of the subjects were recorded. An aliquot of 5 ml of blood was aseptically collected for analysis by GastroPanel® (Biohit Oyj, Helsinki, Finland) biomarker test for PGI, PGII, G-17 and H.pylori IgG antibodies. GastroPanel results were interpreted using the software application GastroSoft® (Biohit). Statistical analyses were run by Epi info 7.0. The study was agreed by the Jammot Hospital of Yaounde, and ethical clearance was obtained from the National Ethics Committee. Results: Results: A total of 84 subjects were recruited, aged between 17-63 years(mean 37.6 ± 8.9 years). H. pyloriseropositivity (IgG ≥30 EIU) was detected in 68(81.0%) of the subjects. H. pyloriseropositivity was closely associated with low CD4 counts (p = 0.01). Altogether, 26(31.0%) of the subjects presented with AG of the corpus while, hypochlorhydria (acid-free stomach) was detected in 32(38.1%) of the patients. AG and hypochlorhydria were associated with low CD4 counts<200 μl/l (p = 0.01) and (p = 0.005), respectively. Conclusion: H. pylori infection, AG and acid-free stomach were common among HIV/AIDS patients, associated with an increased risk for GC and impaired absorption of micronutrients and some medicines.

Changes of serum pepsinogen level and ABC classification after bariatric surgery

Very few studies have explored the changes of serum pepsinogen after bariatric surgery and no research has evaluated the feasibility of ABC classification to predict gastric cancer risk after bariatric surgery. We enrolled 94 obese subjects that received bariatric surgery, including 41 sleeve gastrectomy (SG) and 53 Roux-en-Y gastric bypass (RYGB). The serum pepsinogen I (PGI), pepsinogen II (PGII), PGI/II ratio and seropositivity of Helicobacter pylori ( H. pylori ) were measured before and one year after surgery. Patients were classified according to ABC classification and post-operative change was evaluated. Preoperatively, four (4.2%) patients were classified into high risk group (classification C and D) for gastric cancer. Significant reduction of PGI, PGII and decrease of PGI/II ratio were noted after bariatric surgery. H. pylori seropositive patients had a greater postoperative change of PGI (-38.6μg/L vs -22.1μg/L, p=0.003) and PGII (-8.0μg/L vs -2.5μg/L, p <0.001) but a less postoperative change of PGI/II ratio (-0.6 vs -2.1, p =0.04) than H. pylori seronegative patients. One year after surgery, the portion of high risk group of ABC classification for gastric cancer increased markedly from 4.2% to 23.7%. Both of SG and RYGB resulted in significant reduction of serum PGI and PGII after bariatric surgery, and significantly influenced the ABC classification. The application of ABC classification for gastric cancer screening was limited after bariatric surgery.

The panoramic picture of pepsinogen gene family with pan‐cancer

BackgroundIt is well known that pepsinogen (PGs), as an important precursor of pepsin performing digestive function, has a good correlation with the occurrence and development of gastric cancer and it is also known that ectopic PGs expression is related to the prognosis of some cancers. However, the panoramic picture of pepsinogen gene family in human cancer is not clear. This study focused on elucidating the expression profile, activated pathway, immune cells infiltration, mutation, and copy number variation of PGs and their potential role in human cancer.MethodBased on the next generation sequence data from TCGA, Oncomine, and CCLE, the molecular changes and clinical correlation of PGs in 33 tumor types were analyzed systematically by R language, including the expression, mutation, and copy number variation of PGs and their correlation with cancer‐related signal transduction pathway, immune cell infiltration, and prognostic potential in different cancers.ResultsPGs expression profiles appear different in 33 tumors. The transcriptional expression of PGs was detected in 16 of all 33 tumors. PGC was highly expressed in cholangiocarcinoma, colon adenocarcinoma, rectum adenocarcinoma, uterine corpus endometrial carcinoma, bladder urothelial carcinoma and breast cancer, while decreased in stomach adenocarcinoma, kidney renal clear cell carcinoma, prostate adenocarcinoma, lung squamous cell carcinoma, and esophageal carcinoma. PGA3, PGA4, and PGA5 were expressed in most normal tissues, but decreased in cancer tissues. PGs expression was significantly related to the activation or inhibition of many signal transduction pathways, in which PGC and PGA5 are more likely to be associated with cancer‐related pathways. PGC participated in 33 regulatory network pathways in pan‐cancer, mainly distributed in stomach adenocarcinoma, esophageal carcinoma, and lung squamous cell carcinoma, respectively. PGC and PGA3 expression were significantly correlated with immune cell infiltration. The results of survival analysis showed that different PGs expression play significantly different prognostic roles in different cancers. PGC was correlated with poor survival in brain lower grade glioma, skin cutaneous melanoma, and higher survival in kidney renal clear cell carcinoma, acute myeloid leukemia, mesothelioma, and uveal melanoma. PGA4 was only associated with higher survival in kidney renal clear cell carcinoma. Genetic variation analysis showed that PGC gene often mutated in uterine corpus endometrial carcinoma and stomach adenocarcinoma had extensive copy number amplification in various tumor types. PGC expression was upregulated with the increase of copy number in cholangiocarcinoma, esophageal carcinoma, and kidney renal papillary cell carcinoma, while in stomach adenocarcinoma, PGC was upregulated regardless of whether the copy number was increased or decreased.ConclusionsPGs was expressed unevenly in a variety of cancer tissues and was related to many carcinogenic pathways and involved in the immune regulation. PGC participated in 33 regulatory pathways in human cancer. Different PGs expression play significantly different prognostic roles in different cancers. The variation of copy number of PGC gene could affect the PGC expression. These findings suggested that PGs, especially PGC have characteristic of broad‐spectrum expression in multiple cancers rather than being confined to the gastric mucosa, which may made PGs be useful biomarkers for prediction/diagnosis/prognosis and effective targets for treatment in human cancer.

Development and validation of a serum microRNA biomarker panel for detecting gastric cancer in a high-risk population

ObjectiveAn unmet need exists for a non-invasive biomarker assay to aid gastric cancer diagnosis. We aimed to develop a serum microRNA (miRNA) panel for identifying patients with all stages of...

Prediction of true Helicobacter pylori-uninfected status using a combination of age, serum antibody and pepsinogen: Logistic regression analysis.

To prevent gastric cancer, it is important to accurately determine the presence of Helicobacter pylori (HP) infection. However, correctly identifying HP-uninfected individuals is difficult when using the combination of HP antibody and pepsinogen (PG). The aim of this study was to discriminate true HP-uninfected individuals from others without the need for endoscopic examination. A total of 684 subjects with no history of HP eradication who underwent a medical checkup at our hospital were enrolled. The "true uninfected individuals" were determined by a negative stool antigen test and no endoscopic findings of HP-associated gastritis. HP antibody was measured by the latex immunoassay method. Logistic regression analysis using a combination of noninvasive parameters was performed to develop a formula for predicting true uninfected individuals. A total of 528 subjects were classified as true uninfected individuals. Logistic regression analysis showed that statistically significant factors for true uninfected individuals were age (p < 0.001), HP antibody (p <0.001), PGI (p <0.001), and PGII (p = 0.012). The areas under the curve (AUCs) for true uninfected individuals were the highest (0.944) upon applying the prediction formula including four parameters: age, HP antibody, PGI, and PGII. Both the sensitivity and the specificity of the four-parameter prediction formula were higher than those of the traditional three-parameter model using HP antibody, PGI, and PGI/II ratio (sensitivity: 93.2% vs. 86.6% and specificity: 88.5% vs. 82.7%). Our findings suggest that a model with a combination of four noninvasive parameters is useful for predicting true HP-uninfected individuals without the need for endoscopic examination.

Establish a Scoring Model for High-Risk Population of Gastric Cancer and Study on the Pattern of Opportunistic Screening.

Objective To investigate and study the related risk factors of gastric cancer (GC) patients, to establish a high-risk scoring model of GC by multiple logistic regression analysis, and to explore the establishment of a GC screening mode with clinical opportunistic screening as the main method, and by using the pattern of opportunistic screening to establish the screening of high-risk GC patients and the choice of screening methods in the clinical outpatient work. Methods Collected the epidemiological questionnaire of 99 GC cases and 284 non-GC patients (other chronic gastric diseases and normal) diagnosed by the General Hospital of Ningxia Medical University from October 2017 to March 2019. Serum pepsinogen (PG) levels were measured by enzyme-linked immunosorbent assay (ELISA) and confirmed Helicobacter pylori (Hp) infection in gastric mucosa tissues by Giemsa staining. Determined the high-risk factors and established a scoring model through unconditional logistic regression model analysis, and the ROC curve determined the cut-off value. Then, we followed up 26 patients of nongastric cancer patients constituted a validation group, which validated the model. Results The high-risk factors of GC included age ≥ 55, male, drinking cellar or well water, family history of GC, Hp infection, PGI ≤ 43.6 μg/L, and PGI/PGII ≤ 2.1. Established the high-risk model: Y = A × age + 30 × gender + 30 × drinking water + 30 × Hp infection + 50 × family history of GC + B × PG level. The ROC curve determined that the cut-off value for high-risk GC population was ≥155, and the area under the curve (AUC) was 0.875, the sensitivity and specificity were 87.9% and 71.5%. Conclusions According to the risk factors of GC, using statistical methods can establish a high-risk scoring model of GC, and the score ≥ 155 is divided into the screening cut-off value for high-risk GC population. Using this model for clinical outpatient GC screening is cost-effective and has high sensitivity and specificity.

Helicobacter pylori-negative Gastric Cancer

&lt;i&gt;Helicobacter pylori (H. pylori)&lt;/i&gt;-negative gastric cancer is diagnosed when gastric malignancies are found in patients in &lt;i&gt;H. pylori&lt;/i&gt;-naïve stomachs. There are four types of noncardiac &lt;i&gt;H. pylori&lt;/i&gt;-negative gastric cancers. The signet ring cell-type poorly cohesive carcinoma is most common, followed by the chief cell-predominant type gastric adenocarcinoma of the fundic gland. Extremely well-differentiated adenocarcinoma of the corpus and well-differentiated pyloric gland cancers are rare outside Japan because of country-specific differences in diagnostic criteria. In endemic areas of &lt;i&gt;H. pylori&lt;/i&gt; infection, strict criteria are required for diagnosing an &lt;i&gt;H. pylori&lt;/i&gt;-naïve stomach. Both invasive and noninvasive &lt;i&gt;H. pylori&lt;/i&gt; tests should show negative results in a subject without a history of &lt;i&gt;H. pylori&lt;/i&gt; infection. Furthermore, the serum pepsinogen (PG) assay and endoscopic findings of the background gastric mucosa are required to discriminate subjects with past infections owing to spontaneous regression or unintended eradication of &lt;i&gt;H. pylori&lt;/i&gt;. There should be no gastric corpus atrophy (PG I ≤70 ng/mL and PG I/II ≤3.0). Gastroscopy should reveal a regular arrangement of collecting venules without gastric xanthoma, metaplastic gastritis, or advanced atrophy over the angle. On biopsy, there should be no gastric atrophy, intestinal metaplasia, neutrophils, or &lt;i&gt;H. pylori&lt;/i&gt; infiltration, and only a mild degree of mononuclear cell infiltration is permitted. The types and characteristics of noncardiac &lt;i&gt;H. pylori&lt;/i&gt;-negative gastric cancers are summarized in this review, along with current diagnostic challenges found in Korea.

Expression and clinical significance of paired- related homeobox 1 and Smad2 in gastric cancer.

China has a high incidence rate and low survival rate of gastric cancer. Therefore, there is a great need to further identify novel oncogenes and clinically applicable molecular targets for the diagnosis and treatment of this disease. Expressions of PRRX1, Smad2, epithelial phenotype marker E-cadherin, and interstitial phenotype vimentin protein in a sample of 64 gastric carcinoma and adjacent nontumorous tissues were detected by immunohistochemistry. Their relationship and correlations with clinicopathological features were analyzed. The positive rates of PRRX1, Smad2, E-cadherin, and vimentin protein in primary tumors were 60.94% (39/64), 59.38% (38/64), 34.38%(22/64), and 64.06% (41/64), respectively. A significant correlation was found among the expression of PRRX1, Smad2, E-cadherin, and vimentin (P < 0.05). Expression of the PRRX1, Smad2, and vimentin protein in gastric cancer tissue was correlated with Borrmann classification, lymph node-positive number, the degree of differentiation, depth of tumor invasion, and serum pepsinogen I (PGI) level (P < 0.05), but not with age, sex, serum carcinoembryonic antigen, serum CA199, or PGI/PGII (P > 0.05). The positive rate of PRRX1 protein expression was positively correlated with the protein expression of Smad2 and vimentin, but negatively correlated with E-cadherin protein. PRRX1, Smad2, and vimentin proteins are associated with Borrmann type, lymph node positives, histologic grade, depth of tumor invasion, and serum PGI levels, all of which contribute to a poor prognosis for patients with gastric cancer.