E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

Handle URI:
http://hdl.handle.net/10754/325253
Title:
E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer
Authors:
Kothandaraman, Narasimhan; Bajic, Vladimir B. ( 0000-0001-5435-4750 ) ; Brendan, Pang NK; Huak, Chan Y; Keow, Peh B; Razvi, Khalil; Salto-Tellez, Manuel; Choolani, Mahesh
Abstract:
Background: 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.Methods: 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.Results: 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.Conclusions: 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. 2010 Kothandaraman et al; licensee BioMed Central Ltd.
KAUST Department:
Computational Bioscience Research Center (CBRC)
Citation:
Kothandaraman N, Bajic VB, Brendan PN, Huak CY, Keow PB, et al. (2010) E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer. BMC Cancer 10: 64. doi:10.1186/1471-2407-10-64.
Publisher:
BioMed Central
Journal:
BMC Cancer
Issue Date:
24-Feb-2010
DOI:
10.1186/1471-2407-10-64
PubMed ID:
20181230
PubMed Central ID:
PMC2841139
Type:
Article
ISSN:
14712407
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorKothandaraman, Narasimhanen
dc.contributor.authorBajic, Vladimir B.en
dc.contributor.authorBrendan, Pang NKen
dc.contributor.authorHuak, Chan Yen
dc.contributor.authorKeow, Peh Ben
dc.contributor.authorRazvi, Khalilen
dc.contributor.authorSalto-Tellez, Manuelen
dc.contributor.authorChoolani, Maheshen
dc.date.accessioned2014-08-27T09:42:40Z-
dc.date.available2014-08-27T09:42:40Z-
dc.date.issued2010-02-24en
dc.identifier.citationKothandaraman N, Bajic VB, Brendan PN, Huak CY, Keow PB, et al. (2010) E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer. BMC Cancer 10: 64. doi:10.1186/1471-2407-10-64.en
dc.identifier.issn14712407en
dc.identifier.pmid20181230en
dc.identifier.doi10.1186/1471-2407-10-64en
dc.identifier.urihttp://hdl.handle.net/10754/325253en
dc.description.abstractBackground: 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.Methods: 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.Results: 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.Conclusions: 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. 2010 Kothandaraman et al; licensee BioMed Central Ltd.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en
dc.subjectbiological markeren
dc.subjectCA 125 antigenen
dc.subjecttranscription factor E2F5en
dc.subjectCA 125 antigenen
dc.subjectE2F5 protein, humanen
dc.subjecttranscription factor E2F5en
dc.subjecttumor markeren
dc.subjectadulten
dc.subjectageden
dc.subjectblood samplingen
dc.subjectcancer diagnosisen
dc.subjectcancer stagingen
dc.subjectcarcinogenesisen
dc.subjectcell proliferationen
dc.subjectdiagnostic accuracyen
dc.subjectdrug targetingen
dc.subjectgene overexpressionen
dc.subjecthuman tissueen
dc.subjecthypothesisen
dc.subjectmajor clinical studyen
dc.subjectovary canceren
dc.subjectsensitivity and specificityen
dc.subjecttissue microarrayen
dc.subjectWestern blottingen
dc.subjectalgorithmen
dc.subjectbiosynthesisen
dc.subjectdisease courseen
dc.subjectgene expression regulationen
dc.subjectmetabolismen
dc.subjectmetastasisen
dc.subjectmiddle ageden
dc.subjectovary tumoren
dc.subjectphysiologyen
dc.subjectreproducibilityen
dc.subjectAdulten
dc.subjectAgeden
dc.subjectAlgorithmsen
dc.subjectCA-125 Antigenen
dc.subjectDisease Progressionen
dc.subjectE2F5 Transcription Factoren
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectMiddle Ageden
dc.subjectNeoplasm Metastasisen
dc.subjectOvarian Neoplasmsen
dc.subjectReproducibility of Resultsen
dc.subjectSensitivity and Specificityen
dc.subjectTumor Markers, Biologicalen
dc.titleE2F5 status significantly improves malignancy diagnosis of epithelial ovarian canceren
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalBMC Canceren
dc.identifier.pmcidPMC2841139en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDiagnostic Biomarker Discovery Laboratory, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, 5 Lower Kent Ridge Road, 119074, Singaporeen
dc.contributor.institutionDepartment of Pathology, National University Health System, Yong Loo Lin School of Medicine, 119074, Singaporeen
dc.contributor.institutionNational University Medical Institutes, Yong Loo Lin School of Medicine, National University Health System, 119074, Singaporeen
dc.contributor.institutionSouthend Hospital NHS Trust, Westcliff-on-Sea, Essex, United Kingdomen
dc.contributor.institutionBasildon and Thurrock University Hospital NHS, Foundation Trust, Basildon, Essex, United Kingdomen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorBajic, Vladimir B.en

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