Details

Autor(en) / Beteiligte

• YOSHIHARA, Kosuke
• TSUNODA, Tatsuhiko
• NOGAWA, Takayoshi
• MATSUMURA, Noriomi
• UDAGAWA, Yasuhiro
• SAITO, Tsuyoshi
• ITAMOCHI, Hiroaki
• TAKANO, Masashi
• MIYAGI, Etsuko
• SUDO, Tamotsu
• USHIJIMA, Kimio
• IWASE, Haruko
• SHIGEMIZU, Daichi
• SEKI, Hiroyuki
• TERAO, Yasuhisa
• ENOMOTO, Takayuki
• MIKAMI, Mikio
• AKAZAWA, Kohei
• TSUDA, Hitoshi
• MORIYA, Takuya
• TAJIMA, Atsushi
• INOUE, Ituro
• TANAKA, Kenichi
• FUJIWARA, Hiroyuki
• HATAE, Masayuki
• FUJIWARA, Hisaya
• MASUZAKI, Hideaki
• KATABUCHI, Hidetaka
• KAWAKAMI, Yosuke
• OKAMOTO, Aikou

Titel

High-Risk Ovarian Cancer Based on 126-Gene Expression Signature Is Uniquely Characterized by Downregulation of Antigen Presentation Pathway

Ist Teil von

• Clinical cancer research, 2012-03, Vol.18 (5), p.1374-1385

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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.