Differences in Gut Virome Related to Barrett Esophagus and Esophageal Adenocarcinoma.
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SUBMITTER: Ma T
PROVIDER: S-EPMC8401523 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimThe aim of this study is to determine the prevalence of Barrett esophagus (BE) in first-degree relatives of patients with esophageal adenocarcinoma (EAC) and Barrett high-grade dysplasia (HGD).MethodsAfter Institutional Review Board approval, first-degree relatives of patients with EAC/HGD underwent unsedated ultrathin transnasal endoscopy (UUTNE) with biopsy. BE was suspected if any salmon-colored epithelial tongues were seen above the gastroesophageal junction. A diagnosis of BE was made only if biopsy from these areas confirmed columnar-lined epithelium with intestinal metaplasia.ResultsFrom 23 families, 47 first-degree relatives underwent ultrathin transnasal endoscopy and 1 patient underwent routine upper endoscopy with sedation as part of this study. The mean age of cases was 44.4 years. All patients tolerated the procedure well and there were no procedure-related complications. BE was suspected in 16 (34%) patients and confirmed in 13 of 16 (27.7%) patients. There were 4 long segments (>3 cm) and 9 short segments (<3 cm) of BE.ConclusionThere is a significantly higher than expected prevalence of BE in first-degree relatives of patients with EAC/HGD. This should be taken in to consideration to develop further screening guidelines. Further work is needed to confirm these findings. Unsedated transnasal endoscopy is a safe and well-tolerated method for BE screening.
| S-EPMC3189338 | biostudies-literature
Project description:Barrett esophagus (BE) occurs in 1% to 10% of the general population and is believed to be the precursor of esophageal adenocarcinoma (EAC). The incidence of EAC has increased 350% in the last 3 decades without clear etiology. Finding predisposition genes may improve premorbid risk assessment, genetic counseling, and management. Genome-wide multiplatform approaches may lead to the identification of genes important in BE/EAC development.To identify risk alleles or mutated genes associated with BE/EAC.Model-free linkage analyses of 21 concordant-affected sibling pairs with BE/EAC and 11 discordant sibling pairs (2005-2006). Significant germline genomic regions in independent prospectively accrued series of 176 white patients with BE/EAC and 200 ancestry-matched controls (2007-2010) were validated and fine mapped. Integrating data from these significant genomic regions with somatic gene expression data from 19 BE/EAC tissues yielded 12 "priority" candidate genes for mutation analysis (2010). Genes that showed mutations in cases but not in controls were further screened in an independent prospectively accrued validation series of 58 cases (2010).Identification of germline mutations in genes associated with BE/EAC cases. Functional interrogation of the most commonly mutated gene.Three major genes, MSR1, ASCC1, and CTHRC1 were associated with BE/EAC (all P < .001). In addition, 13 patients (11.2%) with BE/EAC carried germline mutations in MSR1, ASCC1, or CTHRC1. MSR1 was the most frequently mutated, with 8 of 116 (proportion, 0.069; 95% confidence interval [CI], 0.030-0.130; P < .001) cases with c.877C>T (p.R293X). An independent validation series confirmed germline MSR1 mutations in 2 of 58 cases (proportion, 0.035; 95% CI, 0.004-0.120; P = .09). MSR1 mutation resulted in CCND1 up-regulation in peripheral-protein lysate. Immunohistochemistry of BE tissues in MSR1-mutation carriers showed increased nuclear expression of CCND1.MSR1 was significantly associated with the presence of BE/EAC in derivation and validation samples, although it was only present in a small percentage of the cases.
| S-EPMC3574553 | biostudies-literature
Project description:This study fills a gap in literature by providing contemporary real-world evidence on the prevalence of patients with gastroesophageal reflux disease (GERD), Barrett esophagus (BE), and Barrett esophagus-related neoplasia (BERN) and their upper endoscopy utilization patterns in the United States. A retrospective cohort study design was used: adults with GERD, nondysplastic Barrett esophagus (NDBE), and BERN (indefinite for dysplasia [IND], low-grade dysplasia [LGD], high-grade dysplasia [HGD], or esophageal adenocarcinoma [EAC]) were identified from the MarketScan databases (January 01, 2015-December 31, 2019). For each disease stage, prevalence of adults in commercial claims by calendar year, annual number of upper endoscopies per patient and time between upper endoscopies were reported. In 2019, in commercial claims (N = 12,363,227), the annual prevalence rate of GERD was 13.7% and 0.70% for BE/BERN, among which, 87.1% had NDBE, 6.8% had IND, 2.3% had LGD, 1.0% had HGD, and 2.8% had EAC. From 2015-2019, the study included 3,310,385 patients with GERD, 172,481 with NDBE, 11,516 with IND, 4332 with LGD, 1549 with HGD, and 11,676 with EAC. Annual mean number of upper endoscopies was 0.20 per patient for GERD, 0.37 per patient for NDBE, 0.43 for IND, 0.58 for LGD, and 0.87 for HGD. Median time (months) to second upper endoscopy was 38.10 for NDBE, 36.63 for IND, 22.63 for LGD, and 11.90 for HGD. Upper endoscopy utilization increased from GERD to BE to BERN, and time between upper endoscopies decreased as the disease stage progressed from BE to BERN, with less frequent utilization in BERN than what would be expected from guideline recommendations for surveillance.
| S-EPMC10036066 | biostudies-literature
Project description:Aberrant DNA methylation (DNAm) is a feature of most types of cancers. Genome-wide DNAm profiling has been performed successfully on tumor tissue DNA samples. However, the invasive procedure limits the utility of tumor tissue for epidemiological studies. While recent data indicate that cell-free circulating DNAm (cfDNAm) profiles reflect DNAm status in corresponding tumor tissues, no studies have examined the association of cfDNAm with cancer or precursors on a genome-wide scale. The objective of this pilot study was to evaluate the putative significance of genome-wide cfDNAm profiles in esophageal adenocarcinoma (EA) and Barrett esophagus (BE, EA precursor). We performed genome-wide DNAm profiling in EA tissue DNA (n = 8) and matched serum DNA (n = 8), in serum DNA of BE (n = 10), and in healthy controls (n = 10) using the Infinium HumanMethylation27 BeadChip that covers 27,578 CpG loci in 14,495 genes. We found that cfDNAm profiles were highly correlated to DNAm profiles in matched tumor tissue DNA (r = 0.92) in patients with EA. We selected the most differentially methylated loci to perform hierarchical clustering analysis. We found that 911 loci can discriminate perfectly between EA and control samples, 554 loci can separate EA from BE samples, and 46 loci can distinguish BE from control samples. These results suggest that genome-wide cfDNAm profiles are highly consistent with DNAm profiles detected in corresponding tumor tissues. Differential cfDNAm profiling may be a useful approach for the noninvasive screening of EA and EA premalignant lesions.
| S-EPMC3281939 | biostudies-literature
Project description:Esophageal adenocarcinoma currently has one of the most rapidly increasing tumor incidences in the United States, with the vast majority of cases occurring on the backdrop of metaplastic epithelium (Barrett esophagus). The availability of appropriate cell line models is essential for maintaining the pace of esophageal cancer research and for pre-clinical validation of new therapeutic modalities. The identity of several of the widely utilized esophageal adenocarcinoma cell lines (BIC-1, SEG-1 and TE-7) have recently been called into question. Here we describe the establishment and characterization of a bona fide esophageal cancer cell line, JH-EsoAd1, from a patient with Barrett-associated adenocarcinoma. The rapid dissemination of this cancer cell line to the esophageal cancer research community should help ameliorate the current scarcity of preclinical models in this disease.
| S-EPMC3596869 | biostudies-literature
Project description:Esophageal adenocarcinoma is a major cause of cancer-related morbidity and mortality in Western countries. The incidences of esophageal adenocarcinoma and its precursor Barrett's esophagus have increased substantially in the last four decades. Current care guidelines recommend that endoscopy be used for the early detection and monitoring of patients with Barrett's esophagus; however, the efficacy of this approach is unclear. To prevent the increasing morbidity and mortality from esophageal adenocarcinoma, there is a tremendous need for early detection and surveillance biomarker assays that are accurate, low-cost, and clinically feasible to implement. The last decade has seen remarkable advances in the development of minimally invasive molecular biomarkers, an effort led in large part by the Early Detection Research Network (EDRN). Advances in multi-omics analysis, the development of swallowable cytology collection devices, and emerging technology have led to promising assays that are likely to be implemented into clinical care in the next decade. In this review, an updated overview of the molecular pathology of Barrett's esophagus and esophageal adenocarcinoma and emerging molecular biomarker assays, as well as the role of EDRN in biomarker discovery and validation, will be discussed.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."
| S-EPMC7710621 | biostudies-literature
Project description:The increasing incidence of esophageal adenocarcinoma (EAC) is mirrored by the increasing prevalence of Barrett esophagus, a precursor lesion resulting in a large number of individuals "at risk" for this lethal malignancy. Among patients with Barrett esophagus, only about 0.3% annually will develop EAC. Because large numbers of patients are followed in endoscopic surveillance, there is a need for risk prediction among a growing population of patients with Barrett esophagus. We identified four potential biomarkers from an inflammation (IL1β)-dependent mouse model of Barrett esophagus and tested them in 189 patients with Barrett esophagus with and without high-grade dysplasia (HGD)/early cancer (T1). The primary goal was to distinguish patients with Barrett esophagus with no evidence of dysplasia from those with dysplasia. Increasing stem cell marker LGR5 and niche cell marker DCLK1 and decreasing differentiation marker (secretory mucus cells, TFF2+ cells) correlated with elevated tumor score in the mouse. Having outlined the origin of those markers in the Barrett esophagus mouse model, we showed the applicability for human Barrett esophagus. We compared 94 patients with nondysplastic Barrett esophagus tissue with 95 patients with Barrett esophagus and HGD or early cancer. Low levels of TFF2 (AUC 87.2%) provided the best discrimination between nondysplastic Barrett esophagus and Barrett esophagus with cancer, followed by high levels of DCLK1 (AUC 83.4%), low goblet cell ratio (AUC 79.4%), and high LGR5 (AUC 71.4%). The goblet cell ratio, rather than the presence of goblet cells per se, was found to be an important discriminator. These findings may be useful in developing future risk prediction models for patients with Barrett esophagus and ultimately to improve EAC surveillance. Cancer Prev Res; 10(1); 55-66. ©2016 AACR.
| S-EPMC5219855 | biostudies-literature
Project description:BackgroundThe tissue specificity and robustness of miRNAs may aid risk prediction in individuals diagnosed with Barrett's esophagus. As an initial step, we assessed whether miRNAs can positively distinguish esophageal adenocarcinoma from the precursor metaplasia Barrett's esophagus.MethodsIn a case-control study of 150 esophageal adenocarcinomas frequency matched to 148 Barrett's esophagus cases, we quantitated expression of 800 human miRNAs in formalin-fixed paraffin-embedded tissue RNA using NanoString miRNA v2. We tested differences in detection by case group using the χ(2) test and differences in expression using the Wilcoxon rank-sum test. Bonferroni-corrected statistical significance threshold was set at P < 6.25E-05. Sensitivity and specificity were assessed for the most significant miRNAs using 5-fold cross-validation.ResultsWe observed 46 distinct miRNAs significantly increased in esophageal adenocarcinoma compared with Barrett's esophagus, 35 of which remained when restricted to T1b and T2 malignancies. Three miRNAs (miR-663b, miR-421, and miR-502-5p) were detected in >80% esophageal adenocarcinoma, but <20% of Barrett's esophagus. Seven miRNAs (miR-4286, miR-630, miR-575, miR-494, miR-320e, miR-4488, and miR-4508) exhibited the most extreme differences in expression with >5-fold increases. Using 5-fold cross-validation, we repeated feature (miR) selection and case-control prediction and computed performance criteria. Each of the five folds selected the same top 10 miRNAs, which, together, provided 98% sensitivity and 95% specificity.ConclusionThis study provides evidence that tissue miRNA profiles can discriminate esophageal adenocarcinoma from Barrett's esophagus. This large analysis has identified miRNAs that merit further investigation in relation to pathogenesis and diagnosis of esophageal adenocarcinoma.ImpactThese candidate miRNAs may provide a means for improved risk stratification and more cost-effective surveillance.
| S-EPMC4779694 | biostudies-literature
Project description:Barrett esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), a cancer that continues to have a poor 5-year survival rate of 20%. Current BE screening strategies aim to detect BE and EAC at early, curable stages, but the majority of patients with EAC are diagnosed outside of BE screening and surveillance programs. Guidelines around the world suggest screening for BE in patients with gastroesophageal reflux disease (GERD) and additional demographic and clinical risk factors using high-definition white-light endoscopy (HDWLE). However, current strategies relying on HDWLE are problematic with high direct and indirect costs, procedural risks, and limitations in patient selection owing to the low sensitivity of GERD as a risk factor for detection of BE. In an effort to address these shortcomings, a variety of other screening strategies are under investigation, including risk prediction algorithms, noninvasive cell collection devices, and other new technologies to make screening more efficient and cost-effective. At this time, only cell collection devices have been integrated into professional guidelines, and clinical implementation of alternatives to endoscopy has lagged. In the future, screening may be personalized using a combination of different screening modalities. This article discusses the current state of BE screening and new approaches that may alter the future of screening.
| S-EPMC10524417 | biostudies-literature
Project description:Preliminary studies suggested a possible correlation of microbiota with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), where the need for tools to ameliorate its poor prognosis is mandatory. We explored the potential signature of esophageal microbiota and its predicted functional profile along the continuous spectrum from BE to EAC. We analyzed through 16S-based amplicon sequencing the mucosal microbiota and the microbiota-related functional predictions in 10 BE and 6 EAC patients compared with 10 controls, exploring also potential differences between the metaplastic mucosa (BEM) and the adjacent normal areas of BE patients (BEU). BEM and EAC showed a higher level of ? and ?-diversity. BEM evidenced a decrease of Streptococcus and an increase of Prevotella, Actinobacillus, Veillonella, and Leptotrichia. EAC displayed a striking reduction of Streptococcus, with an increase of Prevotella, Veillonella and Leptotrichia. LefSe analysis identified Leptotrichia as the main taxa distinguishing EAC. BEM showed a decreased ?-diversity compared with BEU and a reduction of Bacteroidetes, Prevotella and Fusobacterium. Functional predictions identified peculiar profiles for each group with a high potential for replication and repair in BEM; an upregulated energy, replication and signaling metabolisms, with the fatty-acids biosynthesis and nitrogen and D-alanine pathways down-regulated in EAC. Our pilot study identifies a unique microbial structure and function profile for BE and EAC, as well as for metaplastic and near-normal areas. It proposes a new concept for BE, which could be intended not only as the histological, but, also, as the microbial closest precursor of EAC. This requires further larger follow-up studies, but opens intriguing horizons towards innovative diagnostic and therapeutic options for EAC.
| S-EPMC7199943 | biostudies-literature