Signaling pathways activation profiles make better markers of cancer than expression of individual genes
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Nikolay M. Borisov1,2, Nadezhda V. Terekhanova1,3, Alexander M. Aliper1,3, Larisa S. Venkova1,2, Philip Yu Smirnov1,2, Sergey Roumiantsev1,3, Mikhail B. Korzinkin1,2, Alex A. Zhavoronkov1,3,4, Anton A. Buzdin1,3,4
1Pathway Pharmaceuticals, Wan Chai, Hong Kong, Hong Kong SAR
2Laboratory of Systems Biology, A.I. Burnasyan Federal Medical Biophysical Center, Moscow, 123182, Russia
3Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, 117198, Russia
4Group for Genomic Regulation of Cell Signaling Systems, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia
Anton Buzdin, e-mail: firstname.lastname@example.org
Key words: Cancer, Intracellular signaling pathway activation, Gene expression, Transcriptome profiling, Molecular markers, AUC
Received: July 16, 2014 Accepted: August 16, 2014 Published: October 13, 2014
Identification of reliable and accurate molecular markers remains one of the major challenges of contemporary biomedicine. We developed a new bioinformatic technique termed OncoFinder that for the first time enables to quantatively measure activation of intracellular signaling pathways basing on transcriptomic data. Signaling pathways regulate all major cellular events in health and disease. Here, we showed that the Pathway Activation Strength (PAS) value itself may serve as the biomarker for cancer, and compared it with the “traditional” molecular markers based on the expression of individual genes. We applied OncoFinder to profile gene expression datasets for the nine human cancer types including bladder cancer, basal cell carcinoma, glioblastoma, hepatocellular carcinoma, lung adenocarcinoma, oral tongue squamous cell carcinoma, primary melanoma, prostate cancer and renal cancer, totally 292 cancer and 128 normal tissue samples taken from the Gene expression omnibus (GEO) repository. We profiled activation of 82 signaling pathways that involve ~2700 gene products. For 9/9 of the cancer types tested, the PAS values showed better area-under-the-curve (AUC) scores compared to the individual genes enclosing each of the pathways. These results evidence that the PAS values can be used as a new type of cancer biomarkers, superior to the traditional gene expression biomarkers.
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