Novel robust biomarkers for human bladder cancer based on activation of intracellular signaling pathways

We recently proposed a new bioinformatic algorithm called OncoFinder for quantifying the activation of intracellular signaling pathways. It was proved advantageous for minimizing errors of high-throughput gene expression analyses and showed strong potential for identifying new biomarkers. Here, for...

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Bibliographic Details
Published in:Oncotarget 2014-10, Vol.5 (19), p.9022-9032
Main Authors: Lezhnina, Ksenia, Kovalchuk, Olga, Zhavoronkov, Alexander A, Korzinkin, Mikhail B, Zabolotneva, Anastasia A, Shegay, Peter V, Sokov, Dmitry G, Gaifullin, Nurshat M, Rusakov, Igor G, Aliper, Alexander M, Roumiantsev, Sergey A, Alekseev, Boris Y, Borisov, Nikolay M, Buzdin, Anton A
Format: Article
Language:English
Subjects:
Algorithms
Biomarkers, Tumor - genetics
Computational Biology - methods
Gene Expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Oligonucleotide Array Sequence Analysis - methods
Research Paper
Signal Transduction - genetics
Transcriptome - genetics
Urinary Bladder - cytology
Urinary Bladder Neoplasms - genetics
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Summary:We recently proposed a new bioinformatic algorithm called OncoFinder for quantifying the activation of intracellular signaling pathways. It was proved advantageous for minimizing errors of high-throughput gene expression analyses and showed strong potential for identifying new biomarkers. Here, for the first time, we applied OncoFinder for normal and cancerous tissues of the human bladder to identify biomarkers of bladder cancer. Using Illumina HT12v4 microarrays, we profiled gene expression in 17 cancer and seven non-cancerous bladder tissue samples. These experiments were done in two independent laboratories located in Russia and Canada. We calculated pathway activation strength values for the investigated transcriptomes and identified signaling pathways that were regulated differently in bladder cancer (BC) tissues compared with normal controls. We found, for both experimental datasets, 44 signaling pathways that serve as excellent new biomarkers of BC, supported by high area under the curve (AUC) values. We conclude that the OncoFinder approach is highly efficient in finding new biomarkers for cancer. These markers are mathematical functions involving multiple gene products, which distinguishes them from "traditional" expression biomarkers that only assess concentrations of single genes.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.2493