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Detection of cancer-specific epigenomic changes in biofluids: powerful tools in biomarker discovery and application.

ABSTRACT: The genetic and epigenetic material originating from tumour that can be found in body fluids of individuals with cancer harbours tumour-specific alterations and represents an attractive target for biomarker discovery. Epigenetic changes (DNA methylation, histone modifications and non-coding RNAs) are present ubiquitously in virtually all types of human malignancies and may appear in early cancer development, and thus they provide particularly attractive markers with broad applications in diagnostics. In addition, because changes in the epigenome may constitute a signature of specific exposure to certain risk factors, they have the potential to serve as highly specific biomarkers for risk assessment. While reliable detection of cancer-specific epigenetic changes has proven to be technically challenging, a substantial progress has been made in developing the methodologies that allow an efficient and sensitive detection of epigenomic changes using the material originating from body fluids. In this review we discuss the application of epigenomics as a tool for biomarker research, with the focus on the analysis of DNA methylation in biofluids.

SUBMITTER: Nogueira da Costa A

PROVIDER: S-EPMC5528342 | biostudies-other | 2012 Dec

REPOSITORIES: biostudies-other

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Project description:Lung cancer is the leading cause of cancer deaths worldwide. New diagnostics are needed to detect early stage lung cancer because it may be cured with surgery. However, most cases are diagnosed too late for curative surgery. Here we present a comprehensive clinical biomarker study of lung cancer and the first large-scale clinical application of a new aptamer-based proteomic technology to discover blood protein biomarkers in disease.We conducted a multi-center case-control study in archived serum samples from 1,326 subjects from four independent studies of non-small cell lung cancer (NSCLC) in long-term tobacco-exposed populations. Sera were collected and processed under uniform protocols. Case sera were collected from 291 patients within 8 weeks of the first biopsy-proven lung cancer and prior to tumor removal by surgery. Control sera were collected from 1,035 asymptomatic study participants with ? 10 pack-years of cigarette smoking. We measured 813 proteins in each sample with a new aptamer-based proteomic technology, identified 44 candidate biomarkers, and developed a 12-protein panel (cadherin-1, CD30 ligand, endostatin, HSP90?, LRIG3, MIP-4, pleiotrophin, PRKCI, RGM-C, SCF-sR, sL-selectin, and YES) that discriminates NSCLC from controls with 91% sensitivity and 84% specificity in cross-validated training and 89% sensitivity and 83% specificity in a separate verification set, with similar performance for early and late stage NSCLC.This study is a significant advance in clinical proteomics in an area of high unmet clinical need. Our analysis exceeds the breadth and dynamic range of proteome interrogated of previously published clinical studies of broad serum proteome profiling platforms including mass spectrometry, antibody arrays, and autoantibody arrays. The sensitivity and specificity of our 12-biomarker panel improves upon published protein and gene expression panels. Separate verification of classifier performance provides evidence against over-fitting and is encouraging for the next development phase, independent validation. This careful study provides a solid foundation to develop tests sorely needed to identify early stage lung cancer.

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Detection of cancer-specific epigenomic changes in biofluids: powerful tools in biomarker discovery and application.

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