Dataset Information

DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy.

ABSTRACT:

Background

We analysed critically the potential usefulness of RNA- and DNA-based biomarkers in supporting conventional histological diagnostic tests for prostate carcinoma (PCa) detection.

Methods

Microarray profiling of gene expression and DNA methylation was performed on 16 benign prostatic hyperplasia (BPH) and 32 cancerous and non-cancerous prostate samples extracted by radical prostatectomy. The predictive value of the selected biomarkers was validated by qPCR-based methods using tissue samples extracted from the 58 prostates and, separately, using 227 prostate core biopsies.

Results

HOXC6, AMACR and PCA3 expression showed the best discrimination between PCa and BPH. All three genes were previously reported as the most promising mRNA-based markers for distinguishing cancerous lesions from benign prostate lesions; however, none were sufficiently sensitive and specific to meet the criteria for a PCa diagnostic biomarker. By contrast, DNA methylation levels of the APC, TACC2, RARB, DGKZ and HES5 promoter regions achieved high discriminating sensitivity and specificity, with area under the curve (AUCs) reaching 0.95-1.0. Only a small overlap was detected between the DNA methylation levels of PCa-positive and PCa-negative needle biopsies, with AUCs ranging between 0.854 and 0.899.

Conclusions

DNA methylation-based biomarkers reflect the prostate malignancy and might be useful in supporting clinical decisions for suspected PCa following an initial negative prostate biopsy.

SUBMITTER: Paziewska A

PROVIDER: S-EPMC4134497 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Publications

DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy.

Paziewska A A Dabrowska M M Goryca K K Antoniewicz A A Dobruch J J Mikula M M Jarosz D D Zapala L L Borowka A A Ostrowski J J

British journal of cancer 20140617 4

<h4>Background</h4>We analysed critically the potential usefulness of RNA- and DNA-based biomarkers in supporting conventional histological diagnostic tests for prostate carcinoma (PCa) detection.<h4>Methods</h4>Microarray profiling of gene expression and DNA methylation was performed on 16 benign prostatic hyperplasia (BPH) and 32 cancerous and non-cancerous prostate samples extracted by radical prostatectomy. The predictive value of the selected biomarkers was validated by qPCR-based methods u ...[more]

PMID: 24937670

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Project description:DNA methylation change has been useful for cancer biomarker discovery, classification, and potential treatment development. So far, existing methods use either differentially methylated CpG sites or combined CpG sites, namely differentially methylated regions, that can be mapped to genes. However, such methylation signal mapping has limitations. To address these limitations, in this study, we introduced a combinatorial framework using linear regression, differential expression, deep learning method for accurate biological interpretation of DNA methylation through integrating DNA methylation data and corresponding TCGA gene expression data. We demonstrated it for uterine cervical cancer. First, we pre-filtered outliers from the data set and then determined the predicted gene expression value from the pre-filtered methylation data through linear regression. We identified differentially expressed genes (DEGs) by Empirical Bayes test using Limma. Then we applied a deep learning method, "nnet" to classify the cervical cancer label of those DEGs to determine all classification metrics including accuracy and area under curve (AUC) through 10-fold cross validation. We applied our approach to uterine cervical cancer DNA methylation dataset (NCBI accession ID: GSE30760, 27,578 features covering 63 tumor and 152 matched normal samples). After linear regression and differential expression analysis, we obtained 6287 DEGs with false discovery rate (FDR) <0.001. After performing deep learning analysis, we obtained average classification accuracy 90.69% (±1.97%) of the uterine cervical cancerous labels. This performance is better than that of other peer methods. We performed in-degree and out-degree hub gene network analysis using Cytoscape. We reported five top in-degree genes (PAIP2, GRWD1, VPS4B, CRADD and LLPH) and five top out-degree genes (MRPL35, FAM177A1, STAT4, ASPSCR1 and FABP7). After that, we performed KEGG pathway and Gene Ontology enrichment analysis of DEGs using tool WebGestalt(WEB-based Gene SeT AnaLysis Toolkit). In summary, our proposed framework that integrated linear regression, differential expression, deep learning provides a robust approach to better interpret DNA methylation analysis and gene expression data in disease study.

Dataset Information

DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy.

Background

Methods

Results

Conclusions

Publications

DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy.

Similar Datasets

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