Methylated DAPK and APC promoter DNA detection in peripheral blood is significantly associated with apparent residual tumor and outcome

Hoffmann, Andreas-Claudius; Vallböhmer, Daniel; Prenzel, Klaus L.; Metzger, Ralf; Heitmann, Michaela; Neiss, Susanne; Ling, Frederike C.; Hölscher, Arnulf H.; Schneider, Paul M.; Brabender, Jan

doi:10.1007/s00432-009-0564-x

Cited by 48 publications

(29 citation statements)

References 28 publications

(25 reference statements)

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“…However, there was a strong correlation between stage of the tumor and plasma positivity for methylated APC (131). In combination with DAPK methylation, measurement of preoperative APC methylation in peripheral blood was able to discriminate between long (>2.5 years) and short survivors with a sensitivity of 99.9% and specificity of 57.1% (132). Taken together, tracking circulatory DNA methylation changes during EAC development may be an alternative approach to predict early EAC.…”

Section: Outlook-circulating Biomarkersmentioning

confidence: 93%

Early Diagnostic Biomarkers for Esophageal Adenocarcinoma—The Current State of Play

Shah

Saunders

Barbour

et al. 2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Esophageal adenocarcinoma (EAC) is one of the two most common types of esophageal cancer with alarming increase in incidence and very poor prognosis. Aiming to detect EAC early, currently high-risk patients are monitored using an endoscopic-biopsy approach. However, this approach is prone to sampling error and interobserver variability. Diagnostic tissue biomarkers related to genomic and cell-cycle abnormalities have shown promising results, although with current technology these tests are difficult to implement in the screening of high-risk patients for early neoplastic changes. Differential miRNA profiles and aberrant protein glycosylation in tissue samples have been reported to improve performance of existing tissue-based diagnostic biomarkers. In contrast to tissue biomarkers, circulating biomarkers are more amenable to population-screening strategies, due to the ease and low cost of testing. Studies have already shown altered circulating glycans and DNA methylation in BE/EAC, whereas disease-associated changes in circulating miRNA remain to be determined. Future research should focus on identification and validation of these circulating biomarkers in large-scale trials to develop in vitro diagnostic tools to screen population at risk for EAC development. Cancer Epidemiol Biomarkers Prev; 22(7); 1185-209. Ó2013 AACR.

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Section: Outlook-circulating Biomarkersmentioning

confidence: 93%

Early Diagnostic Biomarkers for Esophageal Adenocarcinoma—The Current State of Play

Shah

Saunders

Barbour

et al. 2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Methylation-specific PCR techniques have been employed by most of the studies to quantify the methylation statues of genes ( Table 4). The genomic DNA was treated with bisulphite (a critical step in methylation analysis) in all studies in order to convert unmethylated cytosines of CpG dinucleotides into uracil or UpG [47,75,82]. In the past, researchers had to collect relatively large amounts of clinical samples to avoid DNA degradation during bisulfite treatment, but now, some commercial kits have been developed successfully which enable highly efficient bisulfite conversion, even the amount of starting material is limited.…”

Section: Microsatellite Instabilitymentioning

confidence: 99%

Cell-free circulating tumor DNA in plasma/serum of non-small cell lung cancer

2014

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Non-small cell lung cancer (NSCLC) is the common type of lung cancer, which is the leading cause of cancer death throughout the world. Most patients were diagnosed too late for curative treatment. So, it is necessary to develop a minimal invasive method to identify NSCLC at an early stage. In recent years, cell-free circulating tumor DNA (ctDNA) has attracted increasing attention as a potential tumor marker for its minimal invasive, convenient, and easily accepted properties. The amount of ctDNA in plasma or serum was significantly higher in NSCLC patients than that in healthy controls or patients with benign diseases. Furthermore, many studies have proved an association among tumor stage, tumor grade, lymph node involvement, the number of metastatic sites, tumor response, survival outcome, and the ctDNA levels. Many genetic changes, such as gene mutation, loss of heterozygosity, microsatellite instability, and gene methylation were also found in ctDNA in NSCLC patients. These findings demonstrated that the ctDNA could serve as a viable tool to monitor NSCLC and prompted us to find more sensitive and specific biomarkers for clinical practice, especially monitor these cases with at least one known gene abnormality. Here, we reviewed the evidence of ctDNA in NSCLC and consider possible future applications in patient management.

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“…Studies have shown that DRP-1 is a calcium calmodulin-regulated serine/threonine kinase involved in apoptotic and autophagic cell death, and the suppression of tumors and metastasis (10,11). Decreased or absent DRP-1 expression has been found in a number of tumor cells and tissues, which may be associated with the methylation changes at CpG sites, and play significant roles in tumorigenesis and development (12,13). Ezrin has been demonstrated to be involved in the interactions between the cells and between the cells and the stroma through regulating adhesion molecules and signal transduction.…”

Section: Discussionmentioning

confidence: 99%

DRP-1, ezrin and E-cadherin expression and the association with esophageal squamous cell carcinoma

et al. 2014

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It has been shown that death-associated protein kinase (DAPK) family and E-cadherin play significant roles in the promotion of apoptosis and the suppression of cell adhesion and migration, and are involved in tumor metastasis. Ezrin, a cytoplasmic peripheral membrane protein, has been shown to interact with E-cadherin to participate in the metastasis of tumor cells. The present study aimed to investigate the expression of DRP-1 (a member of the DAPK family), ezrin and E-cadherin in esophageal squamous cell carcinoma (ESCC), and to analyze their association with clinicopathological factors in order to explore their potential in ESCC diagnosis. The expression of these genes was studied in tissue microarrays using in situ hybridization and immunohistochemistry methods in 76 specimens of ESCC and their paracancerous normal squamous epithelium tissues. Expression was statistically analyzed with regard to clinicopathological factors using χ2 and non-parametric tests. The expression level of DRP-1 was significantly different between the ESCC and paracancerous tissues (P<0.05). The expression level was correlated with the depth of invasion and lymph node metastasis (P<0.05). Abnormal E-cadherin expression was found to be associated with a high degree of cancer differentiation and lymph node metastasis (P<0.05). A positive correlation was observed between the expression of DRP-1 and E-cadherin (P<0.05). The expression of ezrin was found to be correlated with the depth of ESCC invasion, the degree of differentiation and lymph node metastasis (P<0.05). The high expression of ezrin has been previously shown to be correlated with the low or absent expression of E-cadherin. In conclusion, in ESCC, the expression levels of DRP-1, ezrin and E-cadherin were all reduced, and this reduction or absence of expression may have been attributed to ESCC tumorigenesis and progression. Simultaneous analyses of DRP-1, ezrin and E-cadherin expression levels would be useful to determine the malignancy and metastatic potential of ESCC, and these genes are consequently of potential use as biomarkers for the diagnosis and prognosis assessment of early-stage ESCC.

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Methylated DAPK and APC promoter DNA detection in peripheral blood is significantly associated with apparent residual tumor and outcome

Cited by 48 publications

References 28 publications

Early Diagnostic Biomarkers for Esophageal Adenocarcinoma—The Current State of Play

Early Diagnostic Biomarkers for Esophageal Adenocarcinoma—The Current State of Play

Cell-free circulating tumor DNA in plasma/serum of non-small cell lung cancer

DRP-1, ezrin and E-cadherin expression and the association with esophageal squamous cell carcinoma

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