Abstract
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.
Highlights
Bladder cancer (BC) is the second most frequent urological cancer and the ninth most common of all cancers
We investigated gene expression profiles generated from 17 clinical BC tissue samples and seven noncancerous bladder tissue samples using Illumina human
We investigated if the uncovered signaling pathway activation strength values may serve as the biomarkers of bladder cancer
Summary
Bladder cancer (BC) is the second most frequent urological cancer and the ninth most common of all cancers. BC incidence varies greatly among different geographic regions (ranging between 1.8–27.1 per 100,000 males and 0.5–4.1 per 100,000 females), with the highest incidences in countries where the dominant population is Caucasoid [2]. BC accounts for 3.1% and 1.8% of the overall cancer mortality in males and females, respectively. Diagnosis is a prerequisite for successful BC treatment. The effectiveness of BC treatment is dramatically decreased and is associated with poor quality of life. Early diagnosis of BC can significantly prolong lifespan as well as quality of life. Associating marker expression with successful medical treatment may provide clues to a more efficient, patient-oriented cancer treatment therapy [6,7,8,9]
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