title: Identification of Prognostic Groups in High-Grade Serous Ovarian Cancer Treated with Platinum-Taxane Chemotherapy.
abstract: Disseminated high-grade serous ovarian cancer (HGS-OvCa) is an aggressive disease treated with platinum and taxane combination therapy. While initial response can be favorable, the disease typically relapses and becomes resistant to treatment. As genomic alterations in HGS-OvCa are heterogeneous, identification of clinically meaningful molecular markers for outcome prediction is challenging. We developed a novel computational approach (PSFinder) that fuses transcriptomics and clinical data to identify HGS-OvCa prognostic subgroups for targeted treatment. Application of PSFinder to transcriptomics data from 180 HGS-OvCa patients treated with platinum-taxane therapy revealed 61 transcript isoforms that characterize two poor and one good survival-associated groups (P = 0.007). These groups were validated in eight independent data sets, including a prospectively collected ovarian cancer cohort. Two poor prognostic groups have distinct expression profiles and are characteristic by increased hypermethylation and stroma-related genes. Integration of the PSFinder signature and BRCA1/2 mutation status allowed even better stratification of HGS-OvCa patients' prognosis. The herein introduced novel and generally applicable computational approach can identify outcome-related subgroups and facilitate the development of precision medicine to overcome drug resistance. A limited set of biomarkers divides HGS-OvCa into three prognostic groups and predicts patients in need of targeted therapies.
authors.affiliation: Research Programs Unit, Genome-Scale Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Pathology, Institute of Biomedicine, Medicity, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Huhtinen
authors.affiliation: Department of Pathology, Institute of Biomedicine, Medicity, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Katja
authors.initials: K
authors.lastname: Kaipio
authors.affiliation: Department of Pathology, Institute of Biomedicine, Medicity, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Piia
authors.initials: P
authors.lastname: Mikkonen
authors.affiliation: Research Programs Unit, Genome-Scale Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Viljami
authors.initials: V
authors.lastname: Aittomäki
authors.affiliation: Research Programs Unit, Genome-Scale Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Rony
authors.initials: R
authors.lastname: Lindell
authors.affiliation: Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Hynninen
authors.affiliation: Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland.
authors.forename: Annika
authors.initials: A
authors.lastname: Auranen
authors.affiliation: Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland.
authors.forename: Seija
authors.initials: S
authors.lastname: Grénman
authors.affiliation: Research Programs Unit, Genome-Scale Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Rainer
authors.initials: R
authors.lastname: Lehtonen
authors.affiliation: Department of Pathology, Institute of Biomedicine, Medicity, University of Turku and Turku University Hospital, Turku, Finland. Auria Biobank, Turku, Finland. sampsa.hautaniemi@helsinki.fi olli.carpen@utu.fi.
authors.forename: Olli
authors.initials: O
authors.lastname: Carpén
authors.affiliation: Research Programs Unit, Genome-Scale Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland. sampsa.hautaniemi@helsinki.fi olli.carpen@utu.fi.
authors.forename: Sampsa
authors.initials: S
authors.lastname: Hautaniemi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001952:Bridged-Ring Compounds; D015331:Cohort Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005819:Genetic Markers; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D015203:Reproducibility of Results; D012984:Software; D043823:Taxoids
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D001952:Bridged-Ring Compounds; D005819:Genetic Markers; D043823:Taxoids; C080625:taxane