Noninvasive, MultiOmic, and Multicompartmental Biomarkers of Reflux Disease: A Systematic Review.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder that may complicate conditions such as obstructive airway disease. Our group has identified predictive biomarkers of GERD in particulate exposed first responders with obstructive airway disease. In addition, GERD diagnosis and treatment is costly and invasive. In light of these clinical concerns, we aimed to systematically review studies identifying noninvasive, multiOmic, and multicompartmental biomarkers of GERD. METHODS: A systematic review of PubMed and Embase was performed using keywords focusing on reflux disease and biomarkers and registered with PROSPERO. We included original human studies in English, articles focusing on noninvasive biomarkers of GERD published after December 31, 2009. GERD subtypes (non-erosive reflux disease and erosive esophagitis) and related conditions (Barrett's Esophagus [BE] and Esophageal Adenocarcinoma). Predictive measures were synthesized and risk of bias assessed (Newcastle-Ottawa Scale). RESULTS: Initial search identified n = 238 studies andn 13 articles remained after applying inclusion/exclusion criteria. Salivary pepsin was the most studied biomarker with significant sensitivity and specificity for GERD. Serum assessment showed elevated levels of Tumor Necrosis Factor-alpha in both GERD and Barrett's. Exhaled breath volatile sulfur compounds and acetic acid were associated with GERD. Oral Microbiome: Models with Lautropia, Streptococcus, and Bacteroidetes showed the greatest discrimination between BE and controls vs Lautropia; ROCAUC 0.94 (95% confidence interval; 0.85-1.00). CONCLUSION: Prior studies identified significant multiOmic, multicompartmental noninvasive biomarker risks for GERD and BE. However, studies have a high risk of bias and the reliability and accuracy of the biomarkers identified are greatly limited, which further highlights the need to discover and validate clinically relevant noninvasive biomarkers of GERD.

Oral and gastric microbiome in relation to gastric intestinal metaplasia.

Evidence suggests that Helicobacter pylori plays a role in gastric cancer (GC) initiation. However, epidemiologic studies on the specific role of other bacteria in the development of GC are lacking. We conducted a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic-net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29-1.50, P = .004-.01) while Lactobacillus gasseri, Streptococcus mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.66-0.76, P = .006-.042) in cases. Species J ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = .005 and .035, respectively), while S mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.61-0.75, P = .024-.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under-represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions.

Use of TP53 reference materials to validate mutations in clinical tissue specimens by single-strand conformational polymorphism analysis.

BACKGROUND: As genetic information moves from basic research laboratories in to the clinical testing environment, there is a critical need for reliable reference materials for the quality assurance of genetic tests. A panel of 12 plasmid clones containing wild-type or point mutations within exons 5-9 have been developed as reference materials for the detection of TP53 mutations. AIM: The goal of this study was to validate the reference materials in providing quality assurance for the detection of TP53 mutations in clinical specimens. METHODS: We studied 33 gynecological samples, 11 apparently normal samples and 22 malignant tumors of various origins. Mutations were identified using single-strand conformational polymorphism analysis with both slab gel and capillary electrophoresis. All DNA samples were amplified with fluorescently labeled PCR primers specific for exons 5-9 for mutation detection. RESULTS: Of the 33 patient samples tested, mutations and polymorphisms were found in six specimens in three of the five exons scanned; no mutations were found in exons 7 or 9. Both a mutation and polymorphism were found in non-malignant specimens from the control group. The mutations were confirmed by DNA sequence analysis of the regions scanned. CONCLUSIONS: Mutations and polymorphisms were detected in the clinical samples. All of the mutations were silent except for one non-conservative mutation in exon 5, codon 181. This study demonstrates the usefulness of the National Institute of Standards and Technology (NIST) TP53 reference panel in TP53 mutation detection in clinical tissue specimens.