E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer
- Equal contributors
1 Diagnostic Biomarker Discovery Laboratory, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, 5 Lower Kent Ridge Road, 119074, Singapore
2 Computational Bioscience Research Center (CBRC), 4700 King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia
3 Department of Pathology, National University Health System, Yong Loo Lin School of Medicine, 119074, Singapore
4 National University Medical Institutes, Yong Loo Lin School of Medicine, National University Health System, 119074 Singapore
5 Southend Hospital NHS Trust, Westcliff-on-Sea, Essex, UK
6 Basildon & Thurrock University Hospital NHS, Foundation Trust, Basildon, Essex, UK
BMC Cancer 2010, 10:64 doi:10.1186/1471-2407-10-64Published: 24 February 2010
Ovarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We hypothesized that over-expressed transcription factors (TFs), as well as those that are driving the expression of the OEC over-expressed genes, could be the key for OEC genesis and potentially useful tissue and serum markers for malignancy associated with OEC.
Using a combination of computational (selection of candidate TF markers and malignancy prediction) and experimental approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease. Our hypothesis was supported by our tissue array experiments that showed E2F5 expression only in OEC samples but not in normal and benign tissues, and by significantly positively biased expression in serum samples done using western blotting studies.
Analysis of clinical cases shows that of the E2F5 status is characteristic for a different population group than one covered by CA125, a conventional OEC biomarker. E2F5 used in different combinations with CA125 for distinguishing malignant cyst from benign cyst shows that the presence of CA125 or E2F5 increases sensitivity of OEC detection to 97.9% (an increase from 87.5% if only CA125 is used) and, more importantly, the presence of both CA125 and E2F5 increases specificity of OEC to 72.5% (an increase from 55% if only CA125 is used). This significantly improved accuracy suggests possibility of an improved diagnostics of OEC. Furthermore, detection of malignancy status in 86 cases (38 benign, 48 early and late OEC) shows that the use of E2F5 status in combination with other clinical characteristics allows for an improved detection of malignant cases with sensitivity, specificity, F-measure and accuracy of 97.92%, 97.37%, 97.92% and 97.67%, respectively.
Overall, our findings, in addition to opening a realistic possibility for improved OEC diagnosis, provide an indirect evidence that a cell-cycle regulatory protein E2F5 might play a significant role in OEC pathogenesis.