Development and validation of PrOTYPE (Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE)

Gene expression-based molecular subtypes of high grade serous tubo-ovarian cancer (HGSOC) are distinguished by differential immune and stromal infiltration and may provide opportunities for the development of targeted therapies. Integration of molecular subtypes into clinical trials has been hindered by inconsistent subtyping methodology. Adopting two independent approaches, we derived and internally validated algorithms for molecular subtype prediction from gene-expression array data in 1650 tumors. We applied resulting models to assign labels to 3829 HGSOCs from the Ovarian Tumor Tissue Analysis (OTTA) consortium evaluated on NanoString. Using the labeled NanoString data, we developed, confirmed, and validated a clinical-grade test and prediction tool. We also used the OTTA dataset to evaluate associations between molecular subtype, biological, and clinical features. A gene expression study from the Ovarian Tumor Tissue Analysis (OTTA) consortium 4077 total samples including 3829 unique high-grade serous ovarian cancer specimens plus controls analyzed on a custom NanoString panel including 513 assay genes (housekeeping genes are also present in raw data). Unique clinical samples are denoted as clinical in the specimen title. Biological replicates are denoted as OTTA2014_####_REPB1 where #### matches a clinical sample. Technical replicates are denoted similarly with REPT1 or XSITE in the sample title. XSITE further denotes sample that are technical replicates but run in different laboratories (experimental site). Only a subset of XSITE samples will be replicates of clinical specimens, others are exclusively for control purpose.