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TI - Development and validation of the gene-expression Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE (PrOTYPE).
JO - Clinical cancer research
VL - 26
IS - 20
SN - 1557-3265
CY - Philadelphia, Pa. [u.a.]
PB - AACR
M1 - DKFZ-2020-01159
SP - 5411-5423
PY - 2020
N1 - 2020 Oct 15;26(20):5411-5423
AB - Gene-expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by non-standardized methods which are not applicable in a clinical setting. We sought to generate a clinical-grade minimal gene-set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features.Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene-expression data from 1650 tumors. We applied resulting models to NanoString data on 3829 HGSOCs from the Ovarian Tumor Tissue Analysis Consortium. We further developed, confirmed, and validated a reduced, minimal gene-set predictor, with methods suitable for a single patient setting.Gene-expression data was used to derive the Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor infiltrating lymphocytes, and outcome. The locked-down clinical-grade PrOTYPE test includes a model with 55 genes that predicted gene-expression subtype with >95
LB - PUB:(DE-HGF)16
C6 - pmid:32554541
DO - DOI:10.1158/1078-0432.CCR-20-0103
UR - https://inrepo02.dkfz.de/record/156842
ER -