title: High-risk ovarian cancer based on 126-gene expression signature is uniquely characterized by downregulation of antigen presentation pathway.
abstract: OBJECTIVE
  High-grade serous ovarian cancers are heterogeneous not only in terms of clinical outcome but also at the molecular level. Our aim was to establish a novel risk classification system based on a gene expression signature for predicting overall survival, leading to suggesting novel therapeutic strategies for high-risk patients.
  
  
  METHODS
  In this large-scale cross-platform study of six microarray data sets consisting of 1,054 ovarian cancer patients, we developed a gene expression signature for predicting overall survival by applying elastic net and 10-fold cross-validation to a Japanese data set A (n = 260) and evaluated the signature in five other data sets. Subsequently, we investigated differences in the biological characteristics between high- and low-risk ovarian cancer groups.
  
  
  RESULTS
  An elastic net analysis identified a 126-gene expression signature for predicting overall survival in patients with ovarian cancer using the Japanese data set A (multivariate analysis, P = 4 × 10(-20)). We validated its predictive ability with five other data sets using multivariate analysis (Tothill's data set, P = 1 × 10(-5); Bonome's data set, P = 0.0033; Dressman's data set, P = 0.0016; TCGA data set, P = 0.0027; Japanese data set B, P = 0.021). Through gene ontology and pathway analyses, we identified a significant reduction in expression of immune-response-related genes, especially on the antigen presentation pathway, in high-risk ovarian cancer patients.
  
  
  CONCLUSIONS
  This risk classification based on the 126-gene expression signature is an accurate predictor of clinical outcome in patients with advanced stage high-grade serous ovarian cancer and has the potential to develop new therapeutic strategies for high-grade serous ovarian cancer patients.
authors.affiliation: Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yoshihara
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Daichi
authors.initials: D
authors.lastname: Shigemizu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hatae
authors.forename: Hisaya
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Masuzaki
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Katabuchi
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Aikou
authors.initials: A
authors.lastname: Okamoto
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Nogawa
authors.forename: Noriomi
authors.initials: N
authors.lastname: Matsumura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Udagawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itamochi
authors.forename: Masashi
authors.initials: M
authors.lastname: Takano
authors.forename: Etsuko
authors.initials: E
authors.lastname: Miyagi
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sudo
authors.forename: Kimio
authors.initials: K
authors.lastname: Ushijima
authors.forename: Haruko
authors.initials: H
authors.lastname: Iwase
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seki
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Terao
authors.forename: Takayuki
authors.initials: T
authors.lastname: Enomoto
authors.forename: Mikio
authors.initials: M
authors.lastname: Mikami
authors.forename: Kohei
authors.initials: K
authors.lastname: Akazawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Takuya
authors.initials: T
authors.lastname: Moriya
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tajima
authors.forename: Ituro
authors.initials: I
authors.lastname: Inoue
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D017951:Antigen Presentation / Q000235:genetics*; D016000:Cluster Analysis; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015398:Signal Transduction; D016019:Survival Analysis