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Team Project

Validation of Early Detection Ovarian Cancer Biomarkers (Team Project)

330
Skates, StevenMassachusetts General Hospital
Potential Proteins (Gene Name) BCAM, AGRN, ANXA2, IGFBP2, GRN, DSG2, A1P6AP2, FBLN1, FOLR1, LIBP1, NPC2, PROS1, SEC1M1, CIGF, DKK3, IGFBP3, LRG1, PLIP, CD248, CD59, CPA4, CST6, DAG1, DSC2, ECM1, EFEMP1, FSTL1, HSPG2, HTRA1, MXRA5, PCOLCE, SERPINA6, TAGLN2;CCDC19, GLOD4, GM2A, PLEC1, PSAP, QSCN6, NUCB1. Potential Proteins (Accession) P30086, P40305, P03973, O43291, Q12889, Q96910, P16422, P19957, P01024, Q9BXX0, P04275, Q9UBY5, O43194, Q86V14, P02760
Proteomics
Breast and Gynecologic Cancers Research
3

Early detection of Ovarian Cancer (OC) is one of the key clinical problems in this disease. We propose a team EDRN project to address the issue of early detection of OC by performing a validation study on candidate protein markers already identified in previous EDRN research or in the literature (e.g. protein products of TCGA identified mutations specific to ovarian cancer). (See appendix for full listing) Biospecimen sources have been identified which include samples obtained at diagnosis and matched controls (Urban, Godwin, Marks, Skates), and longitudinal samples obtained prior to diagnosis (Urban, Skates, Godwin). Bioinformatic filters will be applied to rank the candidates (Diamandis). In order of ranking, candidate proteins for which high quality antibodies are available will be measured by development of ELISAs at JHU (Chan/Zhang) or through NAPPA at DFCI (Anderson/LaBaer), while for other candidates mass spectrometry based selective reaction monitoring (SRM) assays will be developed at PNNL (Rodland). Three milestones are defined. The first two milestones are to assemble the necessary specimens and to develop the qualifying assay(s). The final milestone is to estimate the markers’ sensitivity one year prior to diagnosis at a given high specificity.

1. Rank candidates identified through past research using bioinformatic analyses (GO, KEGG, Ingenuity), including cancer pathway analyses and gene ontology classifications. 2. Attempt to develop assays for top ranked candidates from step 1 with goal of assay development for 50 candidates (using multiplex immunoassays where high quality mAb pairs or mAb/pAb pairs exist, and SRM targeted mass spec for all other candidates) 3. “Rule in” at least 10 and at most 25 candidates based on assay performance in serum biospecimens obtained at diagnosis, achieving minimal clinical sensitivity (> 5%) at 98% specificity. 4. Measure in pooled samples most proximal to diagnosis of ovarian cancer case in screening study, and in matched control samples, minimizing pooling to achieve minimum required volume for SRM in depleted serum. 5. Rank candidates by sensitivity at fixed high specificity 6. Measure up to top 25 candidates from step 5 in individual longitudinal samples from ovarian cancer cases in screening study, and in matched control samples 7. Candidates validated for early detection of ovarian cancer if clinical sensitivity achieved (5% or greater) at 98% specificity at least 1 year prior to clinical detection.
ELISAs, NAPPA and mass spectrometry based selective reaction monitoring (SRM)

No datasets are currently associated with this protocol.


Announcement 09/14/2014

Thank you to everyone who helped make the 9th EDRN Scientific Workshop a success. We look forward to seeing everyone at the 28th EDRN Steering Committee Meeting from March 31-April 2, 2015, in Atlanta, GA.

Announcement 06/05/2014


Funding Opportunity Available

Both RFAs for Molecular and Cellular Characterization of Screen-Detected Lesions have been published.

RFA-CA-14-010.html

and

RFA-CA-14-011.html