Gastric Cancer Conditions Research Articles

Helicobacter Pylori is the Cause of Human Gastric Cancer

Background—Helicobacter pylori (HP) infection has been repeatedly reported to be associated with human gastric cancer (GC). However, Epstein Bar virus (EBV) has been found in gastric cancer tissues too. It is therefore not surprising that it proved difficult to establish a causal relationship between Helicobacter pylori and gastric cancer. A systematic review and meta-analysis of observational studies was performed to re-investigate the relationship between Helicobacter pylori and gastric cancer. Material and methods—The electronic database PubMed was searched for titles and abstracts of studies which investigated the relationship between HP and GC. Four eligible Japanese studies were included in this meta-analysis (196 incident gastric cancers among a total of 14792 individuals). The data available were analysed by new statistical methods. This study considers 5% as a reasonable cut-off for statistical significance. Results—The studies reviewed provided highly significant evidence that a HP infection is a necessary condition of GC. In everyday language, without a helicobacter pylori infection, no human gastric cancer (P Value < .004). In the same respect, the causal relationship between HP and GC was highly significant too. Conclusion—In a systematic review and meta-analysis, it was possible to establish a causal relationship between HP and GC. Helicobacter pylori is the cause of human gastric cancer. Keywords: Helicobacter pylori, human gastric cancer, cause effect relationshi

Gastric epithelial histology and precancerous conditions

The most common histological type of gastric cancer (GC) is gastric adenocarcinoma arising from the gastric epithelium. Less common variants include mesenchymal, lymphoproliferative and neuroendocrine neoplasms. The Lauren scheme classifies GC into intestinal type, diffuse type and mixed type. The WHO classification includes papillary, tubular, mucinous, poorly cohesive and mixed GC. Chronic atrophic gastritis (CAG) and intestinal metaplasia are recommended as common precancerous conditions. No definite precancerous condition of diffuse/poorly/undifferentiated type is recommended. Chronic superficial inflammation and hyperplasia of foveolar cells may be the focus. Presently, the management of early GC and precancerous conditions mainly relies on endoscopy including diagnosis, treatment and surveillance. Management of precancerous conditions promotes the early detection and treatment of early GC, and even prevent the occurrence of GC. In the review, precancerous conditions including CAG, metaplasia, foveolar hyperplasia and gastric hyperplastic polyps derived from the gastric epithelium have been concluded, based on the overview of gastric epithelial histological organization and its renewal.

Bioinformatic Analysis Identified Potentially Prognostic Long Noncoding RNAs and MicroRNAs for Gastric Cancer.

Gastric cancer (GC) is the fifth most common malignant tumor in the world. The present study was performed to discover the potential diagnostic and therapeutic long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) of GC. Data used in this study to identify differentially expressed lncRNAs (DElncRNAs) and miRNAs (DEmiRNAs) were obtained from 187 GC tissues and 32 adjacent nontumor tissues. The total clinical data on GC included 187 cases. The above data were from the TCGA database. RStudio/Bioconductor software was used to conduct univariate analysis, the least absolute shrinkage and selection operator (LASSO) Cox, and multivariate Cox proportional risk regression for the DElncRNAs and DEmiRNAs. Clinical information was analyzed through univariate and multivariate Cox analysis. Results: five lncRNAs (AC007785.3, AC079385.3, LINC00392, LINC01729, and U95743.1) and two miRNAs (hsa-miR-3174, hsa-miR-605) were proven to be independent prognostic indicators of GC. Results of the Kaplan-Meier survival analysis showed that AC007785.3, AC079385.3, LINC01729, miR-3174, and miR-605 were significantly correlated with OS of GC. The target genes of AC079385.3, miR-3174, and miR-605 were obtained and clustered mainly on MAPK and cGMP-PKG signaling pathways. The clinical data showed that age and clinicopathologic stage were correlated with the prognosis of GC. Furthermore, AC007785.3 was associated with metastasis of GC, and miR-3174 was associated with the primary tumor condition of GC. We identified three lncRNAs (AC007785.3, AC079385.3, LINC01729), two miRNAs (miR-3174, miR-605), and clinical factors related to the pathogenesis and prognosis of GC. Our predicted results provide a possible entry point for the study of prognostic markers for GC.

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.
 Objectives: We assessed the prevalence of H. pylori infection, AG and acid-free stomach (hypochlorhydria) amongst HIV/AIDS subjects in Yaounde Cameroon.
 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.
 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<200μl/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.

Germline FFPE inherited cancer panel testing in deceased family members: implications for clinical management of unaffected relatives

Where previously, germline genetic testing in deceased affected relatives was not possible due to the absence of lymphocytic DNA, the North-West-Genomic-Laboratory Hub (NWGLH) has developed and validated next-generation sequencing based gene panels utilising formalin-fixed-paraffin-embedded (FFPE) tissue DNA from deceased individuals. This technology has been utilised in the clinical setting for the management of unaffected relatives seen in the Clinical Genetics Service (CGS). Here we assess the clinical impact. At the time of data collection, the NWGLH had analysed 180 FFPE tissue samples from deceased affected individuals: 134 from breast and/or ovarian cancer cases for germline variants in the BRCA1/BRCA2 genes and 46 from colorectal, gastric, ovarian and endometrial cancer cases for germline variants in a panel of 13 genes implicated in inherited colorectal cancer and gastric cancer conditions. Successful analysis was achieved in 140/180 cases (78%). In total, 29 germline pathogenic/likely pathogenic variants were identified in autosomal dominant cancer predisposition genes where the gene was pertinent to the cancer family history (including BRCA1/BRCA2, the mismatch-repair genes and APC). Of the 180 cases, the impact of the result on clinical management of unaffected relatives was known in 143 cases. Of these, the results in 54 cases (38%) directly impacted the clinical management of relatives seen by the CGS. This included changes to risk assessments, screening recommendations and the availability of predictive genetic testing to unaffected relatives. Our data demonstrate how FFPE testing in deceased relatives is an accurate and informative tool in the clinical management of patients referred to the CGS.

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.

P57: The first Siberian experience of gastric cancer riskometry: Prospective “case-control” study

Gastric cancer (GC) remains one of the most important gastrointestinal cancers worldwide. The incidence and mortality rate from GC in Russia is higher in comparison with other European countries and USA. It should be noted that riskometry for the GC doesn’t exist. Parallel assessment of pepsinogen I (PG I), pepsinogen II (PG II), PG I/PG II ratio and gastrin-17 (G-17), as well as antibodies to Helicobacter pylori is an exact and validated set of stomach-specific biomarkers that reflect the extent and grade of gastric atrophy as a main premalignant condition for GC. To study the diagnostic and predicting value of biomarkers of atrophic gastritis (AG) in retro-prospective cohort case-control study in Siberian population. General population sample was surveyed in Novosibirsk in 2003–2005 (10.000 subjects aged 45–69 years). Each serum sample was deeply frozen and stored. In 2008 and 2012 this database was compared with the data of the Population Cancer Registry. As a result of cross-sectional analysis of two databases 60 novel cases of GC were identified until 2011. For each case of GC, an appropriate control case was selected at the ratio 1:2 matching the area of residence, sex and age. Finally, 156 serum samples (52 – GC group and 104 – control group) were available for the analysis using a panel of serum biomarkers “Gastropanel” (Biohit, Finland). Criteria for “Gastropanel” in the diagnosis of AG were used: PG I <30μg/l, PG II <3μg/l, the ratio PG I/PG II <3, the level of basal G-17<1 pmol/l, and the presence of antibodies to H. pylori. Mean level of biomarkers did not differ between those with, and without GC, with the exception for PG I/PGII ratio, which was significantly lower in GC group. Indicators of gastric atrophy (OR; 95% CI) were associated with GC for PG I (2.9; 1.3–6.4), PG II (9.0; 1.8–44.3), and PG I/PG II (3.3; 1.5–7.3), but neither for G-17 (0.7, 0.4–1.6), nor for the presence of antibodies to H. pylori (0.4; 0.1–1.3). Multivariate regression analysis including sex, age of the patients, all biomarkers of “Gastropanel” confirmed PG I and PGI/PGII ratio as the most powerful indicators in the model. Atrophy Index (AI) was calculated as a sum of abnormal parameters of gastric atrophy (PG I, PG I/PG II ratio and G-17, see Table, ∗p < 0.019; ∗∗p < 0.006). AI 3 (all biomarkers below normal range) was more common in GC patients than in controls. GroupsSeverity of atrophy (Atrophy Index score) (%)Empty Cell3210Gastric cancer14.0∗∗20.010.056.0Control2.210.811.875.3∗ As a first step in the development of GC riskometry was found that noninvasive set of serological biomarkers is an informative and non-expensive tool for the early detection of GC in population-based retrospective cohort survey in Siberian population. Low levels of PGI and PGI/PGII ratio were proven as the most valuable prognostic factors. The low level of G-17 as a single index did not significantly predict the risk of GC.

Ultrasensitive silicon nanowire for real-world gas sensing: noninvasive diagnosis of cancer from breath volatolome.

We report on an ultrasensitive, molecularly modified silicon nanowire field effect transistor that brings together the lock-and-key and cross-reactive sensing worlds for the diagnosis of (gastric) cancer from exhaled volatolome. The sensor is able to selectively detect volatile organic compounds (VOCs) that are linked with gastric cancer conditions in exhaled breath and to discriminate them from environmental VOCs that exist in exhaled breath samples but do not relate to the gastric cancer per se. Using breath samples collected from actual patients with gastric cancer and from volunteers who do not have cancer, blind analysis validated the ability of the reported sensor to discriminate between gastric cancer and control conditions with >85% accuracy, irrespective of important confounding factors such as tobacco consumption and gender. The reported sensing approach paves the way to use the power of silicon nanowires for simple, inexpensive, portable, and noninvasive diagnosis of cancer and other disease conditions.

Hypoxia-Inducible lncRNA-AK058003 Promotes Gastric Cancer Metastasis by Targeting γ-Synuclein

Hypoxia has been implicated as a crucial microenvironmental factor that induces cancer metastasis. We previously reported that hypoxia could promote gastric cancer (GC) metastasis, but the underlying mechanisms are not clear. Long noncoding RNAs (lncRNAs) have recently emerged as important regulators of carcinogenesis that act on multiple pathways. However, whether lncRNAs are involved in hypoxia-induced GC metastasis remains unknown. In this study, we investigated the differentially expressed lncRNAs resulting from hypoxia-induced GC and normoxia conditions using microarrays and validated our results through real-time quantitative polymerase chain reaction. We found an lncRNA, AK058003, that is upregulated by hypoxia. AK058003 is frequently upregulated in GC samples and promotes GC migration and invasion in vivo and in vitro. Furthermore, AK058003 can mediate the metastasis of hypoxia-induced GC cells. Next, we identified γ-synuclein (SNCG), which is a metastasis-related gene regulated by AK058003. In addition, we found that the expression of SNCG is positively correlated with that of AK058003 in the clinical GC samples used in our study. Furthermore, we found that the SNCG gene CpG island methylation was significantly increased in GC cells depleted of AK058003. Intriguingly, SNCG expression is also increased by hypoxia, and SNCG upregulation by AK058003 mediates hypoxia-induced GC cell metastasis. These results advance our understanding of the role of lncRNA-AK058003 as a regulator of hypoxia signaling, and this newly identified hypoxia/lncRNA-AK058003/SNCG pathway may help in the development of new therapeutics.

A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions

Background:Upper digestive endoscopy with biopsy and histopathological evaluation of the biopsy material is the standard method for diagnosing gastric cancer (GC). However, this procedure may not be widely available for screening in the developing world, whereas in developed countries endoscopy is frequently used without major clinical gain. There is a high demand for a simple and non-invasive test for selecting the individuals at increased risk that should undergo the endoscopic examination. Here, we studied the feasibility of a nanomaterial-based breath test for identifying GC among patients with gastric complaints.Methods:Alveolar exhaled breath samples from 130 patients with gastric complaints (37 GC/32 ulcers / 61 less severe conditions) that underwent endoscopy/biopsy were analyzed using nanomaterial-based sensors. Predictive models were built employing discriminant factor analysis (DFA) pattern recognition, and their stability against possible confounding factors (alcohol/tobacco consumption; Helicobacter pylori) was tested. Classification success was determined (i) using leave-one-out cross-validation and (ii) by randomly blinding 25% of the samples as a validation set. Complementary chemical analysis of the breath samples was performed using gas chromatography coupled with mass spectrometry.Results:Three DFA models were developed that achieved excellent discrimination between the subpopulations: (i) GC vs benign gastric conditions, among all the patients (89% sensitivity; 90% specificity); (ii) early stage GC (I and II) vs late stage (III and IV), among GC patients (89% sensitivity; 94% specificity); and (iii) ulcer vs less severe, among benign conditions (84% sensitivity; 87% specificity). The models were insensitive against the tested confounding factors. Chemical analysis found that five volatile organic compounds (2-propenenitrile, 2-butoxy-ethanol, furfural, 6-methyl-5-hepten-2-one and isoprene) were significantly elevated in patients with GC and/or peptic ulcer, as compared with less severe gastric conditions. The concentrations both in the room air and in the breath samples were in the single p.p.b.v range, except in the case of isoprene.Conclusion:The preliminary results of this pilot study could open a new and promising avenue to diagnose GC and distinguish it from other gastric diseases. It should be noted that the applied methods are complementary and the potential marker compounds identified by gas-chromatography/mass spectrometry are not necessarily responsible for the differences in the sensor responses. Although this pilot study does not allow drawing far-reaching conclusions, the encouraging preliminary results presented here have initiated a large multicentre clinical trial to confirm the observed patterns for GC and benign gastric conditions.

Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project

In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection. In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII(®)). By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4). Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.

Helicobacter Pylori Infection and Chronic Atrophic Gastritis, a Precursor Condition of Gastric Cancer, Among Asian Immigrants in the United States

Helicobacter Pylori Infection and Chronic Atrophic Gastritis, a Precursor Condition of Gastric Cancer, Among Asian Immigrants in the United States