期刊
ONCOTARGET
卷 5, 期 20, 页码 10198-10205出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2548
关键词
Cancer; Intracellular signaling pathway activation; Gene expression; Transcriptome profiling; Molecular markers; AUC
资金
- Russian Foundation for Basic Research [12-04-33094]
- Presidium of the Russian Academy of Sciences
- First Oncology Research and Advisory Center (Moscow, Russia)
- UMA Foundation (Moscow)
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 similar to 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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