Strategic Approach to Validating Methylated Genes as Biomarkers for Breast Cancer

Wang, Ke; Srivastava, Sudhir

doi:10.1158/1940-6207.capr-09-0098

Cited by 16 publications

(12 citation statements)

References 50 publications

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“… 37 Moreover, such DNA methylation-based biomarkers of disease can be also used for risk stratification and may have utility in personalized medicine. 38 In addition, both genetic and epigenetic abnormalities can be used in monitoring the effect of chemopreventive drugs. 38 Therefore, the findings of this study may represent a novel and valuable therapeutic approach for melanoma.…”

Section: Discussionmentioning

confidence: 99%

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Identification of epigenetically altered genes and potential gene targets in melanoma using bioinformatic methods

Duan

Jiang

Wei

et al. 2017

OTT

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This study aimed to analyze epigenetically and genetically altered genes in melanoma to get a better understanding of the molecular circuitry of melanoma and identify potential gene targets for the treatment of melanoma. The microarray data of GSE31879, including mRNA expression profiles (seven melanoma and four melanocyte samples) and DNA methylation profiles (seven melanoma and five melanocyte samples), were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated positions (DMPs) were screened using the linear models for microarray data (limma) package in melanoma compared with melanocyte samples. Gene ontology (GO) and pathway enrichment analysis of the DEGs were carried out using the Database for Annotation, Visualization, and Integrated Discovery. Moreover, differentially methylated genes (DMGs) were identified, and a transcriptional regulatory network was constructed using the University of California Santa Cruz genome browser database. A total of 1,215 DEGs (199 upregulated and 1,016 downregulated) and 14,094 DMPs (10,450 upregulated and 3,644 downregulated) were identified in melanoma compared with melanocyte samples. Additionally, the upregulated and downregulated DEGs were significantly associated with different GO terms and pathways, such as pigment cell differentiation, biosynthesis, and metabolism. Furthermore, the transcriptional regulatory network showed that DMGs such as Aristaless-related homeobox (ARX), damage-specific DNA binding protein 2 (DDB2), and myelin basic protein (MBP) had higher node degrees. Our results showed that several methylated genes (ARX, DDB2, and MBP) may be involved in melanoma progression.

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Section: Discussionmentioning

confidence: 99%

“… 38 In addition, both genetic and epigenetic abnormalities can be used in monitoring the effect of chemopreventive drugs. 38 Therefore, the findings of this study may represent a novel and valuable therapeutic approach for melanoma.…”

Section: Discussionmentioning

confidence: 99%

Identification of epigenetically altered genes and potential gene targets in melanoma using bioinformatic methods

Duan

Jiang

Wei

et al. 2017

OTT

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“…This may be a result of not including matched normal tissue, but only Sss I-treated human peripheral white-blood-cell DNA from the same patient or from healthy subjects as a control. This method of comparison cannot accurately reflect the number of positive methylation cases, as methylation modification is influenced by many factor, including lifestyle, environmental exposures, ethnicity, age and tissue heterogeneity ( 40 , 45 ). The present study used breast cancer tissue and matched healthy breast tissue and methylation percentage of a particular area was assessed using the 2 −ΔΔCq method.…”

Section: Methodsmentioning

confidence: 99%

Aberrant promoter methylation of PCDH10 as a potential diagnostic and prognostic biomarker for patients with breast cancer

Liu

Shi

et al. 2018

Oncol Lett

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Protocadherin-10 (PCDH10) is a tumor suppressor gene. Its expression level is downregulated by promoter methylation in certain types of human tumors. The aim of the present study was to examine the expression level and promoter methylation status of PCDH10 in breast cancer cells and to evaluate the association of PCDH10 methylation and tumor progression and prognosis. MethyLight was used to detect the methylation status of PCDH10 in breast cancer tissues and healthy breast tissues. Reverse transcription-quantitative polymerase chain reaction was used to assess the mRNA expression level of PCDH10, as well as to evaluate the association between PCDH10 methylation and clinicopathological features, along with patients' overall survival (OS). PCDH10 5′-C-phosphate-G-3′ (CpG) methylated sites were identified in tumor tissues and matched healthy tissues (n=392). Tumor tissues and matched healthy tissues exhibited identifiable PCR results, with PCDH10 gene promoter methylation identified in ductal carcinoma in situ (66%), invasive ductal carcinoma (82%), invasive ductal carcinoma with lymph node metastasis (85.32%) and hereditary breast cancer tissues (72.37%). PCDH10 mRNA expression was significantly decreased in breast cancer tissues compared with healthy breast tissues (P=0.032). PCDH10 methylation was associated with tumor size (P=0.004), but not associated with other clinical factors. Survival analysis revealed that the patients exhibiting methylated-PCDH10 had significantly poorer OS times than patients exhibiting unmethylated-PCDH10 (P<0.0001). Receiver operating characteristic analysis indicated a sensitivity of 75%, a specificity of 62.5%, and an area under the curve of 0.682 for PCDH10. Additionally, the results of the present study indicated that PCDH10 methylation status may be a useful diagnostic and prognostic evaluation biomarker for breast cancer. The results suggested that PCDH10 methylation is a common occurrence in primary breast cancer and is associated with poor survival rates among patients with breast cancer.

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“…The sensitivity of mammography is only moderate, and moreover is greatly affected by age and breast density [22]. Similarly, the use of USG for breast cancer screening incurs a high rate of false negative results, particularly in women with dense breast tissue.…”

Section: Current Procedures For Breast Cancer Detection and Diagnosismentioning

confidence: 99%

Detection of Methylated Circulating DNA as Noninvasive Biomarkers for Breast Cancer Diagnosis

2017

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Internationally, breast cancer is the most common female cancer, and is induced by a combination of environmental, genetic, and epigenetic risk factors. Despite the advancement of imaging techniques, invasive sampling of breast epithelial cells is the only definitive diagnostic procedure for patients with breast cancer. To date, molecular biomarkers with high sensitivity and specificity for the screening and early detection of breast cancer are lacking. Recent evidence suggests that the detection of methylated circulating cell-free DNA in the peripheral blood of patients with cancer may be a promising quantitative and noninvasive method for cancer diagnosis. Methylation detection based on a multi-gene panel, rather than on the methylation status of a single gene, may be used to increase the sensitivity and specificity of breast cancer screening. In this review, the results of 14 relevant studies, investigating the efficacy of cell-free DNA methylation screening for breast cancer diagnosis, have been summarized. The genetic risk factors for breast cancer, the methods used for breast cancer detection, and the techniques and limitations related to the detection of cell-free DNA methylation status, have also been reviewed and discussed. From this review, we conclude that the analysis of peripheral blood or other samples to detect differentially methylated cell-free DNA is a promising technique for use in clinical settings, and may improve the sensitivity of screening for both, early detection and disease relapse, and thus improve the future prognosis of patients with breast cancer.

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Strategic Approach to Validating Methylated Genes as Biomarkers for Breast Cancer

Cited by 16 publications

References 50 publications

Identification of epigenetically altered genes and potential gene targets in melanoma using bioinformatic methods

Identification of epigenetically altered genes and potential gene targets in melanoma using bioinformatic methods

Aberrant promoter methylation of PCDH10 as a potential diagnostic and prognostic biomarker for patients with breast cancer

Detection of Methylated Circulating DNA as Noninvasive Biomarkers for Breast Cancer Diagnosis

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