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. 2017 May 9;8(19):31948-31958.
doi: 10.18632/oncotarget.16654.

DFNA5 promoter methylation a marker for breast tumorigenesis (VSports在线直播)

Lieselot Croes  1   2 , Ken Op de Beeck  1   2 , Patrick Pauwels  2 , Wim Vanden Berghe  3 , Marc Peeters  2 , Erik Fransen  1   4 , Guy Van Camp  1
Affiliations

DFNA5 promoter methylation a marker for breast tumorigenesis

Lieselot Croes et al. Oncotarget. .

Abstract

Background: Identification of methylation markers that are sensitive and specific for breast cancer may improve early detection. We hypothesize that DFNA5 promoter methylation can be a valuable epigenetic biomarker, based upon strong indications for its role as tumor suppressor gene and its function in regulated cell death VSports手机版. .

Results: Statistically different levels of methylation were seen, with always very low levels in healthy breast reduction samples, very high levels in part of the adenocarcinoma samples and slightly increased levels in part of the normal tissue samples adjacent the tumor V体育安卓版. One of the CpGs (CpG4) showed the best differentiation. A ROC curve for DFNA5 CpG4 methylation showed a sensitivity of 61. 8% for the detection of breast cancer with a specificity of 100%. .

Materials and methods: We performed methylation analysis on four CpGs in the DFNA5 promoter region by bisulfite pyrosequencing on 123 primary breast adenocarcinomas and 24 healthy breast reductions. For 16 primary tumors, corresponding histological normal tissue adjacent to the tumor was available V体育ios版. .

Conclusions: We conclude that DFNA5 methylation shows strong potential as a biomarker for detection of breast cancer. Slightly increased methylation in histologically normal breast tissue surrounding the tumor suggests that it may be a good early detection marker VSports最新版本. .

Keywords: DFNA5; DNA methylation; biomarker; breast cancer; detection V体育平台登录. .

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. DFNA5 CpG4 methylation percentages of primary breast adenocarcinomas compared to normal breast tissues at a distance of the tumor and healthy breast reductions
The plot shows DFNA5 CpG4 promoter methylation percentages in 123 untreated, primary breast adenocarcinomas; 16 untreated, histological normal breast tissues at a distance of the tumor and 24 untreated, healthy breast reduction samples of non-cancerous patients. The optimal methylation cutoff (7.0%), determined by a ROC analysis, showed DFNA5 CpG4 methylation in 61.8% of 123 breast adenocarcinomas, in 43.8% of 16 histological normal breast tissues at a distance of the tumor and in none of 24 healthy breast reduction samples. The horizontal black lines indicate the median DFNA5 CpG4 methylation percentage per group.
Figure 2
Figure 2. DFNA5 CpG4 methylation percentage as a biomarker for breast adenocarcinomas
Sensitivity and specificity at various cutoff values for our dataset (123 breast adenocarcinomas and 24 healthy breast reductions) are shown in the ROC curve. The full line represents the ROC curve. The dotted line represents the line of no discrimination between tumor and healthy breast samples. The determined optimal cutoff value for DFNA5 CpG4 methylation is 7.0%.
Figure 3
Figure 3. DFNA5 CpG4 methylation percentages in 16 paired breast adenocarcinomas and histologically normal breast tissues at a distance of the tumor
The x-axis shows the DFNA5 CpG4 methylation percentage and each number on the y-axis depicts a patient, from whom both breast adenocarcinoma tissue and histologically normal breast tissue at a distance of the tumor were available.
Figure 4
Figure 4. Kaplan Meier analyses of 5-year OS, 5-year PFS and 5-year DFS
(A) shows 5-year OS in 120 breast adenocarcinoma patients, 11 patients died in 5 years after diagnosis. In (B) 5-year PFS in 111 breast adenocarcinoma patients is shown. In only 8 patients recurrence or metastatic disease occurred. (C) shows 5-year DFS in 116 patients. In 5 years after diagnosis a total of 14 patients have had metastatic disease, recurrence or died.
See this image and copyright information in PMC

References

    1. Van Laer L, Huizing EH, Verstreken M, van Zuijlen D, Wauters JG, Bossuyt PJ, van de Heyning P, McGuirt WT, Smith RJ, Willems PJ, Legan PK, Richardson GP, van Camp G. Nonsyndromic hearing impairment is associated with a mutation in DFNA5. Nat Genet. 1998;20:194–7. doi: 10.1038/2503. - DOI - PubMed
    1. Van Rossom S, Op de Beeck K, Franssens V, Swinnen E, Schepers A, Ghillebert R, Caldara M, van Camp G, Winderickx J. The splicing mutant of the human tumor suppressor protein DFNA5 induces programmed cell death when expressed in the yeast Saccharomyces cerevisiae. Front Oncol. 2012;2:77. doi: 10.3389/fonc.2012.00077. - DOI - PMC - PubMed
    1. Van Rossom S, Op de Beeck K, Hristovska V, Winderickx J, van Camp G. The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways. Front Cell Neurosci. 2015;9:231. doi: 10.3389/fncel.2015.00231. - DOI - PMC - PubMed
    1. Op de Beeck K, van Camp G, Thys S, Cools N, Callebaut I, Vrijens K, van Nassauw L, van Tendeloo VF, Timmermans JP, van Laer L. The DFNA5 gene, responsible for hearing loss and involved in cancer, encodes a novel apoptosis-inducing protein. Eur J Hum Genet. 2011;19:965–73. doi: 10.1038/ejhg.2011.63. - "VSports手机版" DOI - PMC - PubMed
    1. Wang C, Tang L, Shen D, Wang C, Yuan Q, Gao W, Wang Y, Xu R, Zhang H. The expression and regulation of DFNA5 in human hepatocellular carcinoma DFNA5 in hepatocellular carcinoma. Mol Biol Rep. 2013;40:6525–31. doi: 10.1007/s11033-013-2581-8. - DOI - PubMed

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