In Silico discovery of transcription factors as potential diagnostic biomarkers of ovarian cancer

Author:

Kaur Mandeep,MacPherson Cameron R,Schmeier Sebastian,Narasimhan Kothandaraman,Choolani Mahesh,Bajic Vladimir B

Abstract

Abstract Background Our study focuses on identifying potential biomarkers for diagnosis and early detection of ovarian cancer (OC) through the study of transcription regulation of genes affected by estrogen hormone. Results The results are based on a set of 323 experimentally validated OC-associated genes compiled from several databases, and their subset controlled by estrogen. For these two gene sets we computationally determined transcription factors (TFs) that putatively regulate transcription initiation. We ranked these TFs based on the number of genes they are likely to control. In this way, we selected 17 top-ranked TFs as potential key regulators and thus possible biomarkers for a set of 323 OC-associated genes. For 77 estrogen controlled genes from this set we identified three unique TFs as potential biomarkers. Conclusions We introduced a new methodology to identify potential diagnostic biomarkers for OC. This report is the first bioinformatics study that explores multiple transcriptional regulators of OC-associated genes as potential diagnostic biomarkers in connection with estrogen responsiveness. We show that 64% of TF biomarkers identified in our study are validated based on real-time data from microarray expression studies. As an illustration, our method could identify CP2 that in combination with CA125 has been reported to be sensitive in diagnosing ovarian tumors.

Publisher

Springer Science and Business Media LLC

Subject

Applied Mathematics,Computer Science Applications,Molecular Biology,Modeling and Simulation,Structural Biology

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