Abstract A23: Allele specific regulation of esophageal cancer related gene 2 by miR-1322 in esophageal squamous cell carcinoma

The incidence and histological type of esophageal cancer are highly variable depending on geographic location and race/ethnicity. Here we want to determine if racial difference exists in the molecular features of esophageal cancer. We firstly confirmed that the incidence rate of esophagus adenocarcinoma (EA) was higher in Whites than in Asians and Blacks, while the incidence of esophageal squamous cell carcinoma (ESCC) was highest in Asians. Then we compared the genome-wide somatic mutations, methylation, and gene expression to identify differential genes by race. The mutation frequencies of some genes in the same pathway showed opposite difference between Asian and White patients, but their functional effects to the pathway may be consistent. The global patterns of methylation and expression were similar, which reflected the common characteristics of ESCC tumors from different populations. A small number of genes had significant differences between Asians and Whites. More interesting, the racial differences of COL11A1 were consistent across multiple molecular levels, with higher mutation frequency, higher methylation, and lower expression in White patients. This indicated that COL11A1 might play important roles in ESCC, especially in White population. Additional studies are needed to further explore their functions in esophageal cancer.

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IDDF2021-ABS-0106 Significance of the expression of iron death-related gene hsbp1 in esophageal squamous cell carcinoma

10.1136/gutjnl-2021-iddf.38 ◽

2021 ◽

Author(s):

Mingxin Zhang ◽

Ning Lu ◽

Qian Li ◽

Manli Cui

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Related Gene

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A Novel Ferroptosis-Related Biomarker Signature to Predict Overall Survival of Esophageal Squamous Cell Carcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.675193 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jiahang Song ◽

Yanhu Liu ◽

Xiang Guan ◽

Xun Zhang ◽

Wenda Yu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Risk Score ◽

Squamous Cell ◽

Risk Model ◽

Expression Profiles ◽

Gene Signature ◽

Immune Checkpoints ◽

Related Gene

Esophageal squamous cell carcinoma (ESCC) accounts for the main esophageal cancer (ESCA) type, which is also associated with the greatest malignant grade and low survival rates worldwide. Ferroptosis is recently discovered as a kind of programmed cell death, which is indicated in various reports to be involved in the regulation of tumor biological behaviors. This work focused on the comprehensive evaluation of the association between ferroptosis-related gene (FRG) expression profiles and prognosis in ESCC patients based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). ALOX12, ALOX12B, ANGPTL7, DRD4, MAPK9, SLC38A1, and ZNF419 were selected to develop a novel ferroptosis-related gene signature for GEO and TCGA cohorts. The prognostic risk model exactly classified patients who had diverse survival outcomes. In addition, this study identified the ferroptosis-related signature as a factor to independently predict the risk of ESCC. Thereafter, we also constructed the prognosis nomogram by incorporating clinical factors and risk score, and the calibration plots illustrated good prognostic performance. Moreover, the association of the risk score with immune checkpoints was observed. Collectively, the proposed ferroptosis-related gene signature in our study is effective and has a potential clinical application to predict the prognosis of ESCC.

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Aberrant hypermethylation-mediated downregulation of antisense lncRNA ZNF667-AS1 and its sense gene ZNF667 correlate with progression and prognosis of esophageal squamous cell carcinoma

Cell Death and Disease ◽

10.1038/s41419-019-2171-3 ◽

2019 ◽

Vol 10 (12) ◽

Cited By ~ 12

Author(s):

Zhiming Dong ◽

Shengmian Li ◽

Xuan Wu ◽

Yunfeng Niu ◽

Xiaoliang Liang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Cancer ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Cells ◽

Squamous Cell ◽

Proximal Promoter ◽

Migration And Invasion ◽

Esophageal Cancer Cells ◽

E Cadherin

AbstractNatural antisense lncRNAs can interfere with their corresponding sense transcript to elicit concordant or discordant regulation. LncRNA ZNF667-AS1 and its sense gene ZNF667 were found to be downregulated in esophageal squamous cell carcinoma (ESCC) tissues by RNA sequencing; however, the exact roles of both genes in ESCC occurrence and development have not been clarified. This study was to investigate the expression patterns, epigenetic inactivation mechanisms, function, and prognostic significance of ZNF667-AS1 and ZNF667 in ESCC tumorigenesis. Frequent downregulation of ZNF667-AS1 and ZNF667 was detected in esophageal cancer cells and ESCC tissues. The expression levels of ZNF667-AS1 and ZNF667 were significantly reversed by treatment with 5-Aza-dC and TSA in esophageal cancer cell lines. The CpG sites hypermethylation within proximal promoter influenced the binding ability of transcription factor E2F1 to the binding sites and then affected the transcription and expression of ZNF667-AS1 and ZNF667. Overexpression of ZNF667-AS1 and ZNF667 suppressed the viability, migration, and invasion of esophageal cancer cells in vitro. Overexpression of ZNF667-AS1 increased mRNA and protein expression level of ZNF667. ZNF667-AS1 interacts with and recruits TET1 to its target gene ZNF667 and E-cadherin to hydrolyze 5′-mc to 5′-hmc and further activates their expression, meanwhile, ZNF667-AS1 also interacts with UTX to decrease histone H3K27 tri-methylation to activate ZNF667 and E-cadherin expression. Furthermore, ZNF667-AS1 or ZNF667 expression and promoter methylation status were correlated with ESCC patients’ survival. Thus, these findings suggest that ZNF667-AS1 and ZNF667 may act as tumor suppressors and may serve as potential targets for antitumor therapy.

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Germline BRCA1 mutated esophageal squamous cell carcinoma

Rare Tumors ◽

10.1177/2036361320972218 ◽

2020 ◽

Vol 12 ◽

pp. 203636132097221

Author(s):

Jason Starr ◽

Brian Ramnaraign

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Cancer ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Brca Mutation ◽

Brca Mutations ◽

Ovarian Cancers ◽

First Case

The most common associated malignancies with BRCA mutations include breast and ovarian cancers. Less common malignancies associated with BRCA mutation include: pancreatic, prostate, colon, gastric, and biliary cancers. Esophageal cancer, particularly squamous cell carcinoma, has rarely been reported to harbor BRCA mutations. Here we report, to our knowledge, the first case of germline BRCA1 mutated associated esophageal squamous cell carcinoma.

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Estimating molecular variability of patient-derived xenografts of esophageal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13649 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13649-e13649

Author(s):

Tatiana P. Protasova ◽

Natalya N. Timoshkina ◽

Evgeniy N. Kolesnikov ◽

Mikhail A. Averkin ◽

Umar Muhmadovich Gaziev ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Cancer ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Molecular Genetic ◽

Human Tumor ◽

Genetic Characteristics ◽

Pdx Model ◽

Genetic Subtype

e13649 Background: The survival of patients with esophageal squamous cell carcinoma depends not only on clinical signs (TNM, tumor site), but also on the molecular genetic subtype of the tumor. Identification of the molecular genetic subtype and the presence/absence of clinically significant mutations is an important step towards finding new effective drugs and choosing the most appropriate therapeutic strategies. A patient-derived xenograft (PDX) model is a valuable resource to solving the problem, provided that the model accurately reproduces the basic clinical and molecular genetic characteristics of a human tumor. Our purpose was to create a PDX model of a human tumor and to study 7 polymorphisms of the xenograft tissue and tissues of a donor tumor. Methods: PDX models of esophageal cancer were produced by transplanting a tumor fragment from a patient with esophageal squamous cell carcinoma to the BALB/c Nude athymic mice (n = 10 for one PDX generation). 5 PDX were generated. 7 polymorphisms (NFE2L2 (c.85G > A), NOTCH1 (c.1379C > T), NOTCH1 (c.1451G > T), ZNF750 (c.414C > A), ZNF750 (c.1621G > A), SMARCA4 (c.2272C > T), KMT2D (c.15508C > T)) were determined by the HRM analysis in tissues of each PDX generation and in the donor tumor. Results: All examined samples demonstrated the absence of ZNF750 (c.1621G > A) and NOTCH1 (c.1379C > T) polymorphisms and the presence of ZNF750 (c.414C > A), SMARCA4 (c.2272C > T) and KMT2D (c.15508C > T) polymorphisms. Polymorphisms in the NFE2L2 (c.85G > A) gene and in the NOTCH1 (c.1451G > T) gene were found in the F3, F4 and F5 PDX generations, but were absent in the donor tumor and the F1 and F2 generations. Conclusions: Molecular and genetic characteristics of the donor tumor change through several PDX generations. Early PDX generations are recommended for the studies as they better reproduce molecular and genetic characteristics of the original tumors.

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