Abstract
BackgroundOur 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.ResultsThe 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.ConclusionsWe 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.
Highlights
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
This study identified potential biomarkers important for overall transcriptional regulation of OC genes and for a sub-group of OC genes controlled by estrogen
To identify genes controlled by estrogen, two approaches were used: (a) prediction of estrogen response elements (EREs) on the promoters of OC genes, and (b) finding the experimental evidence for estrogen control in published databases
Summary
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. Diagnosis greatly enhances the chances of successful cancer treatment To this date, very few earlydetection approaches have shown promise for routine inactive in the cancer affected tissues under normal physiological conditions and their expression and activities are tightly regulated, these TFs represent highly desirable and logical points of therapeutic interference in cancer development, progression and prognostication [7,8,9], markers for cancer [10], potential prognostic markers [7,11] and targets for drug therapy [12]. We anticipate that the target pool of biomarkers could be revealed by studying specific signatures within the hormone dependent regulatory gene networks
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