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DNA-methylation and autoantibodies based cancer diagnosis from body fluids

Authors:

Christa Noehammer ,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Matthias Wielscher,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Johana Fuchs-Luna,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Istvan Gyurjan,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Manuela Hofner,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Ulrike Kegler,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Linda Stoeger,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Christian Singer,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Friedrich Längle,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Johann Hofbauer,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Andrea Gsur,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Rolf Ziesche,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Klemens Vierlinger,

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Andreas Weinhaeusel

AIT Austrian Institute of Technology, Vienna, Austria, AU
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Abstract

Special focus and aim of our research activities at AIT, the Austrian Institute of Technology, is to define reliable biomarkers suitable for early and non-invasive disease diagnosis from body fluids such as serum/plasma and saliva. Along a selection of research projects, which are described in more detail underneath, we will present and introduce the broad portfolio of high throughput technologies we successfully apply for diagnostic biomarker discovery and validation. As a first show case of successful non-invasive disease biomarker discovery we will present a study where we investigated and compared the genome wide methylation levels of lung cancer patients, patients suffering from lung fibrosis, patients with COPD (chronic obstructive pulmonary disease), and DNA samples derived from healthy lungs. Along this study we could identify specific methylation patterns for each of these lung diseases. After quantitative PCR validation of 240 disease specific methylation markers in the discovery sample set, the 90 top markers were picked and applied for serum testing (n=204). When we applied gradient boosting classification for differential diagnosis of tested lung diseases and healthy controls an AUC value of 0.95 was reached here to separate cancer from all other non-cancer samples whereas in differential diagnosis of healthy-, COPD and fibrosis patients AUC values of 0.71 and 0.49 were obtained for fibrosis, respectively COPD. Thus in case of COPD the presented method may be used to monitor cancer risk within COPD patients. Our second show case comprises a study where we screened cancer patients’ sera for tumor-specific antibody profiles using an in-house developed 16k protein-microarray. This methodology, which will be described in detail, enabled us to define different tumor-associated antigen (TAA) classifier panels for the big 4 cancer entities (breast, colon, prostate and lung cancer) which all showed very promising classification successes in distinction of patients versus controls. We will further present preliminary data obtained when comparing serum and saliva autoantibody profiles of breast-cancer patients and healthy controls.
How to Cite: Noehammer, C., Wielscher, M., Fuchs-Luna, J., Gyurjan, I., Hofner, M., Kegler, U., Stoeger, L., Singer, C., Längle, F., Hofbauer, J., Gsur, A., Ziesche, R., Vierlinger, K. and Weinhaeusel, A., 2015. DNA-methylation and autoantibodies based cancer diagnosis from body fluids. European Journal of Molecular & Clinical Medicine, 2(2), p.64. DOI: http://doi.org/10.1016/j.nhtm.2014.11.032
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Published on 07 Feb 2015.
Peer Reviewed

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