Epigenetics in the Pathogenesis of Esophageal Adenocarcinoma

Kailasam, Aparna; Mittal, Sumeet K.; Agrawal, Devendra K.

doi:10.1111/cts.12242

Cited by 23 publications

(15 citation statements)

References 72 publications

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“…Correlation between RKIP protein expression and clinicopathological characteristics. epigenetic alterations also play significant roles in the development of multiple cancers, including ESCC (30)(31)(32). Among various epigenetic alterations, aberrant DNA methylation (including hypomethylation of oncogenes and hypermethylation of tumor suppressor genes) is the best characterized and most crucial mechanism modulating chromatin structure and the expression levels of oncogenes or tumor suppressor genes, contributing to tumor initiation and further development (33).…”

Section: Discussionmentioning

confidence: 99%

Promoter methylation and expression of Raf kinase inhibitory protein in esophageal squamous cell carcinoma

et al. 2017

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Abstract. Raf kinase inhibitory protein (RKIP) regulates multiple cellular processes, and its downregulation is associated with distinct human cancers. In the present study, the status of RKIP promoter methylation, as well as its expression and clinical significance in esophageal squamous cell carcinoma (ESCC), were examined. The promoter methylation status in the 5'-CpG island of the RKIP gene and the expression level of the RKIP protein were examined using a modified methylation-specific polymerase chain reaction (MSP) method and immunohistochemical staining, respectively, in 77 ESCC samples and matched paratumor normal tissues. The incidence of RKIP promoter methylation was significantly higher in tumor samples (75.3%) than in the matched normal tissues (27.3%; P<0.001). A higher incidence of promoter methylation was also detected in poorly differentiated cancers (93.5%) compared with well-differentiated cancers (50.0%; P<0.001), as well as in tumor samples with positive lymph node metastasis (86.7%) compared with those with negative lymph node metastasis (59.4%; P<0.001). Consistent with the promoter methylation status, the expression level of RKIP was significantly reduced in cancer tissues (36.4%) compared with matched normal tissues (76.6%; P<0.01), as well as in cancers with positive lymph node metastasis (24.4%) compared with those with negative lymph node metastasis (53.1%; P=0.01). Promoter methylation-induced gene silencing significantly correlated with the down regulation of RKIP and the development of ESCC. The results of the present study suggested that the methylation status of the RKIP promoter, when combined with its expression level, may serve as a biomarker for predicting the biological behaviors of ESCC.

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Section: Discussionmentioning

confidence: 99%

Promoter methylation and expression of Raf kinase inhibitory protein in esophageal squamous cell carcinoma

et al. 2017

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“…The well-known risk factors include gastroesophageal reflux, Barrett's esophagus (via metaplasia-dysplasia-neoplasia sequence), obesity, caucasian race, increasing age, alcohol and smoking. The study of lncRNAs in EAC is not too advanced [ 92 ].…”

Section: Lncrnas In Esophageal Cancermentioning

confidence: 99%

LONG-NONCODING RNAs in gastroesophageal cancers

Fanelli

Gasparini

Coati

et al. 2018

Non-coding RNA Research

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Despite continuing improvements in multimodal therapies, gastro-esophageal malignances remain widely prevalent in the population and is characterized by poor overall and disease-free survival rates. Due to the lack of understanding about the pathogenesis and absence of reliable markers, gastro-esophageal cancers are associated with delayed diagnosis. The increasing understanding about cancer's molecular landscape in the recent years, offers the possibility of identifying ‘targetable’ molecular events and in particular facilitates novel treatment strategies and development of biomarkers for early stage diagnosis. At least 98% of our genome is actively transcribed into non-coding RNAs encompassing long non-coding RNAs (lncRNAs) constituted of transcripts longer than 200 nucleotides with no protein-coding capacity. Many studies have demonstrated that lncRNAs are functional genomic elements playing pivotal roles in main oncogenic processes. LncRNA can act at multiple levels developing a complex molecular network that can modulate directly or indirectly the expression of genes involved in tumorigenesis. In this review, we focus on lncRNAs as emerging players in gastro-esophageal carcinogenesis and critically assess their potential as reliable noninvasive biomarkers and in next generation targeted therapies.

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“…It is believed that epigenetics plays a larger role in cancer than originally appreciated [64–66]. This indeed has opened many more avenues for researchers to explore.…”

Section: Genetics and Epigeneticsmentioning

confidence: 99%

Emerging therapeutic targets in esophageal adenocarcinoma

2016

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The incidence of gastro-esophageal disease and associated rate of esophageal adenocarcinoma (EAC) is rising at an exponential rate in the United States. However, research targeting EAC is lagging behind, and much research is needed in the field to identify ways to diagnose EAC early as well as to improve the rate of pathologic complete response (pCR) to systemic therapies. Esophagectomy with subsequent reconstruction is known to be a morbid procedure that significantly impacts a patient's quality of life. If indeed the pCR rate of patients can be improved and those patients destined to be pCR can be identified ahead of time, they may be able to avoid this life-altering procedure. While cancer-specific biological pathways have been thoroughly investigated in other solid malignancies, much remains unexplored in EAC. In this review, we will highlight some of the latest research in the field in regards with EAC, along with new therapeutic targets that are currently being explored. After reviewing conventional treatment and current changes in medical therapy for EAC, we will focus on unchartered grounds such as cancer stem cells, genetics and epigenetics, immunotherapy, and chemoradio-resistant pathways as we simultaneously propose some investigational possibilities that could be applicable to EAC.

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Epigenetics in the Pathogenesis of Esophageal Adenocarcinoma

Cited by 23 publications

References 72 publications

Promoter methylation and expression of Raf kinase inhibitory protein in esophageal squamous cell carcinoma

Promoter methylation and expression of Raf kinase inhibitory protein in esophageal squamous cell carcinoma

LONG-NONCODING RNAs in gastroesophageal cancers

Emerging therapeutic targets in esophageal adenocarcinoma

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