ArticleProceedings of the National Academy of Sciences of the United States of America2012
Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00081354 (Barrett's Esophagus Early Detection Study), which is not on this map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Barrett's Esophagus Early Detection Study
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2015Pooled it
- Imbalance in WNT: retinoic acid signaling dysregulates HOX gene expression: implications for cancer stem cell heterogeneity and CRC patient survival.Stem cells translational medicine · 2026Article
- Intrinsic mechanisms and microenvironmental cues fine-tune plasticity of esophageal progenitors.Nature communications · 2026Article
- Macrophages in tertiary lymphoid structures promote apoptosis of ATF4-positive gastric cancer cells via IL18.Journal of translational medicine · 2025Article
- The Evolving Paradigm of Esophageal and Esophagogastric Junction Adenocarcinoma: Current Insights, Emerging Therapies, and Future Directions.Journal of cancer science and clinical therapeutics · 2025Article
- Article
- Differential Expression of NEK Kinase Family Members in Esophageal Adenocarcinoma and Barrett's Esophagus.Cancers · 2023Article
- TRIM29 hypermethylation drives esophageal cancer progression via suppression of ZNF750.Cell death discovery · 2023Article
- Chromatin modifier developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders.BMC medicine · 2022Article
- A risk variant for Barrett's esophagus and esophageal adenocarcinoma at chr8p23.1 affects enhancer activity and implicates multiple gene targets.Human molecular genetics · 2022Article
- Long noncoding RNA HOXC-AS3 interacts with CDK2 to promote proliferation in hepatocellular carcinoma.Biomarker research · 2022Article
- Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review.Cell death discovery · 2022Review
- Transcription factor-mediated intestinal metaplasia and the role of a shadow enhancer.Genes & development · 2022Article
- Hybrid Stomach-Intestinal Chromatin States Underlie Human Barrett's Metaplasia.Gastroenterology · 2021Article
- HOXA13 in etiology and oncogenic potential of Barrett's esophagus.Nature communications · 2021Article
- Forkhead box F1 induces columnar phenotype and epithelial-to-mesenchymal transition in esophageal squamous cells to initiate Barrett's like metaplasia.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Epithelial expression of Gata4 and Sox2 regulates specification of the squamous-columnar junction via MAPK/ERK signaling in mice.Nature communications · 2021Article
- Characterizing caspase-1 involvement during esophageal disease progression.Cancer immunology, immunotherapy : CII · 2020Article
- Molecular Profile of Barrett's Esophagus and Gastroesophageal Reflux Disease in the Development of Translational Physiological and Pharmacological Studies.International journal of molecular sciences · 2020Article
- ST8SIA6-AS1 promotes hepatocellular carcinoma by absorbing miR-5195-3p to regulate HOXB6.Cancer biology & therapy · 2020Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Barrett esophagus (BE) is a human metaplastic condition that is the only known precursor to esophageal adenocarcinoma. BE is characterized by a posterior intestinal-like phenotype in an anterior organ and therefore it is reminiscent of homeotic transformations, which can occur in transgenic animal models during embryonic development as a consequence of mutations in HOX genes. In humans, acquired deregulation of HOX genes during adulthood has been linked to carcinogenesis; however, little is known about their role in the pathogenesis of premalignant conditions. We hypothesized that HOX genes may be implicated in the development of BE. We demonstrated that three midcluster HOXB genes (HOXB5, HOXB6, and HOXB7) are overexpressed in BE, compared with the anatomically adjacent normal esophagus and gastric cardia. The midcluster HOXB gene signature in BE is identical to that seen in normal colonic epithelium. Ectopic expression of these three genes in normal squamous esophageal cells in vitro induces markers of intestinal differentiation, such as KRT20, MUC2, and VILLIN. In BE-associated adenocarcinoma, the activation midcluster HOXB gene is associated with loss of H3K27me3 and gain of AcH3, compared with normal esophagus. These changes in histone posttranslational modifications correlate with specific chromatin decompaction at the HOXB locus. We suggest that epigenetically regulated alterations of HOX gene expression can trigger changes in the transcriptional program of adult esophageal cells, with implications for the early stages of carcinogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.