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Bioinformatical evaluation of modified nucleosides as biomedical markers in diagnosis of breast cancer
Authors:Bullinger Dino  Fröhlich Holger  Klaus Fabian  Neubauer Hans  Frickenschmidt Antje  Henneges Carsten  Zell Andreas  Laufer Stefan  Gleiter Christoph H  Liebich Hartmut  Kammerer Bernd
Institution:a University Hospital Tübingen, Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, Otfried-Müller-Str. 45, D-72076 Tübingen, Germany
b Center for Bioinformatics Tübingen (ZBIT), Sand 1, D-72076 Tübingen, Germany
c University Hospital Tübingen, Medical Clinic, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany
d Department of Obstetrics and Gynecology, University Hospital Tübingen, Calwerstr. 7, D-72076 Tübingen, Germany
e University of Tübingen, Institute of Pharmacy, Auf der Morgenstelle 8, D-72076 Tübingen, Germany
Abstract:It is known that patients suffering from cancer diseases excrete increased amounts of modified nucleosides with their urine. Especially methylated nucleosides have been proposed to be potential tumor markers for early diagnosis of cancer. For determination of nucleosides in randomly collected urine samples, the nucleosides were extracted using affinity chromatography and then analyzed via reversed phase high-performance liquid chromatography (HPLC) with UV-detection. Eleven nucleosides were quantified in urine samples from 51 breast cancer patients and 65 healthy women.The measured concentrations were used to train a Support Vector Machine (SVM) and a k-nearest-neighbor classifier (k-NN) to discriminate between healthy control subjects and patients suffering from breast cancer. Evaluations of the learned models by computing the leave-one-out error and the prediction error on an independent test set of 29 subjects (15 healthy, 14 breast cancer patients) showed that by using the eleven nucleosides, the occurrence of breast cancer could be forecasted with 86% specificity and 94% sensitivity when using an SVM and 86% for both specificity and sensitivity with the k-NN model.
Keywords:Metabolomics  High performance liquid chromatography with ultraviolett detection (HPLC-UV)  Nucleosides  Breast cancer  Support Vector Machine (SVM)  k-Nearest-neighbor classifier (k-NN)
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