Dataset Information

Epigenetic Alterations in Oesophageal Cancer: Expression and Role of the Involved Enzymes.

ABSTRACT: Oesophageal cancer is a life-threatening disease, accounting for high mortality rates. The poor prognosis of this malignancy is mostly due to late diagnosis and lack of effective therapies for advanced disease. Epigenetic alterations may constitute novel and attractive therapeutic targets, owing to their ubiquity in cancer and their reversible nature. Herein, we offer an overview of the most important studies which compared differences in expression of enzymes that mediate epigenetic alterations between oesophageal cancer and normal mucosa, as well as in vitro data addressing the role of these genes/proteins in oesophageal cancer. Furthermore, The Cancer Genome Atlas database was interrogated for the correlation between expression of these epigenetic markers and standard clinicopathological features. We concluded that most epigenetic players studied thus far are overexpressed in tumours compared to normal tissue. Furthermore, functional assays suggest an oncogenic role for most of those enzymes, supporting their potential as therapeutic targets in oesophageal cancer.

SUBMITTER: Lopes N

PROVIDER: S-EPMC7278932 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Epigenetic Alterations in Oesophageal Cancer: Expression and Role of the Involved Enzymes.

Lopes Nair N Correia Margareta P MP Henrique Rui R Jerónimo Carmen C

International journal of molecular sciences 20200515 10

Oesophageal cancer is a life-threatening disease, accounting for high mortality rates. The poor prognosis of this malignancy is mostly due to late diagnosis and lack of effective therapies for advanced disease. Epigenetic alterations may constitute novel and attractive therapeutic targets, owing to their ubiquity in cancer and their reversible nature. Herein, we offer an overview of the most important studies which compared differences in expression of enzymes that mediate epigenetic alterations ...[more]

PMID: 32429269

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Project description:PADI4 post-translationally converts peptidylarginine to citrulline. PADI4 can disrupt the apoptotic process via the citrullination of histone H3 in the promoter of p53-target genes. The current study focused on PADI4 expression in various subtypes of oesophageal carcinoma (EC) by immunohistochemistry, western blotting and real time PCR. The study also investigated the effect of bile acid deoxycholate (DCA) on PADI4 expression in Eca-109 cells that originated from EC. Apoptosis and DCA-induced toxicity were analyzed by TUNEL, MTT assay and flow cytometry. Additionally, the present study investigated the correlation between single nucleotide polymorphism (SNP) in PADI4 gene and EC risk in Chinese population using Illumina GoldenGate assay. Compared with paraneoplastic tissues, the transcriptional and translational levels of PADI4 were significantly elevated in oesophageal squamous cell carcinoma (ESCC, n=9) and oesophageal adenocarcinoma (EAC, n=5) tissues. Immunolabeling detected expression of PADI4 in ESCC tissues (98.56%, n=139), EAC samples (87.5%, n=16) and oesophageal small cell undifferentiated carcinoma (91.7%, n=12) but not in normal tissues (0%, n=16). Furthermore, PADI4 levels is positively correlated with the pathological classification of ESCC (p=0.009). PADI4 expression levels were consistent with the number of apoptotic cells in the induced Eca-109 cells. rs10437048 [OR= 0.012831; 95% CI, 0.001746~0.094278; p=1.556×10(-12)] were significantly associated with decreased risk of EC, whereas rs41265997 [OR=12.7; 95% CI, 0.857077~33.207214; p=3.896×10(-8)] were significantly associated with increased risk of EC. rs41265997 in exon 3 of PADI4 gene is non-synonymous and converts ACG to ATG resulting in a threonine /methionine conversion at position 274 of the protein. Haplotypes GC that carries the variant alleles for rs2501796 and rs2477134 was significantly associated with increased risk of EC (frequency=0.085, p=0.0256, OR=2.7). The results suggest that PADI4 expression is related to the tumorigenic process of EC and the DCA-induced apoptosis. The PADI4 gene may be a valid EC susceptibility gene.

Dataset Information

Epigenetic Alterations in Oesophageal Cancer: Expression and Role of the Involved Enzymes.

Publications

Epigenetic Alterations in Oesophageal Cancer: Expression and Role of the Involved Enzymes.

Similar Datasets

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