Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas

Ferrer-Torres, Daysha; Nancarrow, Derek J.; Kuick, Rork; Thomas, Dafydd G.; Nadal, Ernest; Lin, Jules; Chang, Andrew C.; Reddy, Rishindra M.; Taylor, Jeremy M. G.; Wang, Thomas D.; Beer, David G.

doi:10.18632/oncotarget.10253

Cited by 14 publications

(16 citation statements)

References 65 publications

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Section: Mrna Extraction and Affymetrix Expression Analysismentioning

confidence: 99%

“…RNA was isolated from the normal esophageal squamous mucosa from individuals selfidentified as either EA or AA, as previously described 10 . mRNA extraction and Human Gene ST 2.1 array (Affymetrix, Santa Clara, CA) hybridizations were performed as previously described 10 . Expression values for each gene were determined using the robust multi-array average (RMA) method 11 in the Bioconductor package 12 of the R statistical platform.…”

Section: Mrna Extraction and Affymetrix Expression Analysismentioning

confidence: 99%

“…An extended normal squamous tissue cohort, consisting of the 12 AA and 12 EA examined by ST 2.1 array, plus an additional 9 AA, 9 EA, and one AA:BE were for quantitative realtime polymerase chain reaction (qRT-PCR) validation of selected gene transcripts. Total RNA was converted to cDNA and used for qRT-PCR as previously described 10 , with details of qRT-PCR primers and analysis provided in Supplementary Methods.…”

Section: Qrt-pcr Validationmentioning

confidence: 99%

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Constitutively Higher Level of GSTT2 in Esophageal Tissues From African Americans Protects Cells Against DNA Damage

et al. 2019

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Section: Mrna Extraction and Affymetrix Expression Analysismentioning

confidence: 99%

Section: Mrna Extraction and Affymetrix Expression Analysismentioning

confidence: 99%

Section: Qrt-pcr Validationmentioning

confidence: 99%

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Constitutively Higher Level of GSTT2 in Esophageal Tissues From African Americans Protects Cells Against DNA Damage

et al. 2019

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“…Indeed, genetic and epigenetic analyses have also consistently shown BE and EAC to be very similar, [28][29][30][31] and one study that sought genomic differences between adenocarcinomas with and without BE failed to reveal molecular differences between the two. 32 Nonetheless, this is fortunate news that, with adequate uptake, screening for BE by upper endoscopy or minimally-invasive non-endoscopic technologies 16,33 could potentially identify and enroll all patients who are at risk for developing EAC into a surveillance program. Practically speaking, this would require very sensitive screening to detect all prevalent BE of any size and location (such as small BE patches at irregular Z-lines) but our results suggest these patients would constitute the majority of future EAC cases if detected.…”

Section: Discussionmentioning

confidence: 99%

Barrett’s esophagus is the precursor of all esophageal adenocarcinomas

Curtius

Rubenstein

Chak

et al. 2020

Preprint

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ObjectiveBarrett's esophagus (BE) is a known precursor to esophageal adenocarcinoma (EAC) but current clinical data have not been consolidated to address whether BE is the origin of all incident EAC, which would reinforce evidence for BE screening efforts. We aimed to answer whether all expected prevalent BE, diagnosed and undiagnosed, could account for all incident EACs in the US cancer registry data. DesignWe used a multi-scale computational model of EAC that includes the evolutionary process from normal esophagus through BE in individuals from the US population. The model was previously calibrated to fit SEER cancer incidence curves. Here we also utilized age-and sexspecific US census data for numbers at-risk. The primary outcome for model validation was the expected number of EAC cases for a given calendar year. Secondary outcomes included the comparisons of resulting model-predicted prevalence of BE and BE-to-EAC progression to the observed prevalence and progression rates. ResultsThe model estimated the total number of EAC cases in 2010 was 9,970 (95% CI 9,140 -11,980), which recapitulates all EAC cases from population data. The model simultaneously predicted 8-9% BE prevalence in high-risk males age 45-55, and 0.1-0.2% non-dysplastic BEto-EAC annual progression in males, consistent with clinical studies. ConclusionThere are no additional EAC cases that plausibly arise in the US population outside the BE pathway. Effective screening of high-risk patients could capture the majority of population destined for EAC progression and decrease mortality through early detection and curative removal of small (pre)cancers during surveillance. Summary Box What is already known about this subject?• Barrett's esophagus (BE) patients have a 40 to 50-fold higher risk of developing esophageal adenocarcinoma (EAC) than the general population yet many remain undiagnosed. • Identified BE patients receiving surveillance can have early cancers discovered endoscopically, which decreases the high overall EAC-associated mortality. • Currently around 90% of patients who develop EAC were never part of a BE surveillance program, and those BE patients on surveillance have a low annual progression rate of 0.1 -0.3% to develop EAC. What are the new findings?• By applying a model that incorporates the evolution from normal cells to BE to EAC in patients, we found that the numbers add up -the expected number of EAC cases in the US population are explained by the published rates of BE described above. • We cohesively examined the published estimates to determine that all EAC likely arises from both identified BE and occult, undiagnosed BE in the population. How might it impact on clinical practice in the foreseeable future?• Based on current best estimates, our findings suggest there is no public health need to seek cases of a non-BE alternative pathway to EAC. • Increasing efforts for effective, sensitive screening and surveillance of the true BE population will decrease EAC mortality in the coming years.

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“…CLND3 encodes Claudin 3, which is associated with the tight junction representing cell-to-cell adhesion (38). The association between CLND3 and cancer remains controversial; upregulation of CLND3 has been reported to act as a biomarker and a predictor of poor prognosis in different types of cancer, including triple-negative breast, oesophageal and gastric cancer (39,40). By contrast, downregulation of CLDN3 has been demonstrated to be associated with the progression and metastasis of lung squamous cell carcinoma (41).…”

Section: Kif11 Expression -------------------------------------------mentioning

confidence: 99%

Identification and validation of core genes for serous ovarian adenocarcinoma via bioinformatics analysis

et al. 2020

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Ovarian cancer is a fatal gynaecological malignancy in women worldwide, and serous ovarian cancer (SOC) is considered the most common histological subtype of this malignancy. Thus, the present study aimed to identify the core genes for SOC via bioinformatics analysis. The GSE18520 and GSE14407 datasets were downloaded from the Gene Expression Omnibus (GEO) database to screen for differentially expressed genes (DEGs) and perform gene set enrichment analysis (GSEA). A protein-protein interaction (PPI) network was constructed to identify the core genes, while The Cancer Genome Atlas (TCGA) database was used to screen for prognosis-associated DEGs. Furthermore, clinical samples were collected for further validation of kinesin family member 11 (KIF11) gene. In the GEO analysis, a total of 198 DEGs were identified, including 81 upregulated and 117 downregulated genes compared SOC to normal tissue. GSEA across the two datasets demonstrated that 16 gene sets, including those involved in the cell cycle and DNA replication, were notably associated with SOC. A PPI network of the DEGs was constructed with 130 nodes and 387 edges. Subsequently, 20 core genes involved in the same top-ranked module were filtered out by submodule analysis. Survival analysis identified three predictive genes for SOC prognosis, including KIF11, CLDN3 and FGF13. KIF11 was identified as a core and predictive gene and thus was further validated using clinical samples. The results demonstrated that KIF11 was upregulated in tumour tissues compared with adjacent normal tissues and was associated with aggressive factors, including tumour grade, TNM stage and lymph node invasion. In conclusions, the present study identified the core genes and gene sets for SOC, thus extending the understanding of SOC occurrence and progression. Furthermore, KIF11 was identified as a promising tumour-promoting gene and a potential target for the diagnosis and treatment of SOC.

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Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas

Cited by 14 publications

References 65 publications

Constitutively Higher Level of GSTT2 in Esophageal Tissues From African Americans Protects Cells Against DNA Damage

Constitutively Higher Level of GSTT2 in Esophageal Tissues From African Americans Protects Cells Against DNA Damage

Barrett’s esophagus is the precursor of all esophageal adenocarcinomas

Identification and validation of core genes for serous ovarian adenocarcinoma via bioinformatics analysis

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