title: Prediction of taxane and platinum sensitivity in ovarian cancer based on gene expression profiles.
abstract: OBJECTIVE
  Prognoses of ovarian cancer (OC) have improved with the paclitaxel-carboplatin regimen. However, it remains unclear which cases exhibit a genuine benefit from taxane or from platinum. We aimed to predict taxane and platinum sensitivity in OC via gene expression.
  
  
  METHODS
  We identified differentially expressed genes in responsive and resistant cases from advanced OC biopsy expression dataset GSE15622, containing responses to paclitaxel or carboplatin monotherapy. These genes generated a scoring system for prediction of drug response by applying single-sample gene set enrichment analysis. Discriminative metrics termed the T-score and C-score were derived.
  
  
  RESULTS
  High C-score levels were significant in responders compared to non-responders in a separate cisplatin treatment dataset (GSE18864, p=0.043). High C-score groups also had significantly better progression-free survival in three OC datasets (The Cancer Genome Atlas, TCGA: p=0.02; GSE9891: p=0.03; GSE30161: p=0.001). In two additional datasets of advanced OC, high T-scores could associate taxane and platinum regimens with better survival than non-taxane and platinum regimens (GSE9891: p<0.0001; GSE3149: p=0.045), whereas in cases with low T-scores, different chemotherapeutic regimens did not result in a significant difference. Assessing TCGA and GSE9891, T-scores were elevated in the C1/Mesenchymal subtype, whereas C-scores were elevated in the C5/Proliferative subtype and were lower in the C1/Mesenchymal subtype (p<0.0001, respectively). C- and T-scores negatively correlated with each other, suggesting complementary roles of taxane and platinum.
  
  
  CONCLUSIONS
  Our proposal and finding of a scoring system that could predict platinum or taxane response could be useful to develop individualized treatments to ovarian cancer.
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Murakami
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Japan. Electronic address: noriomi@kuhp.kyoto-u.ac.jp.
authors.forename: Noriomi
authors.initials: N
authors.lastname: Matsumura
authors.affiliation: Kyoto University Graduate School of Medicine, Center for Medical Education, Life Science Informatics Research Unit, Japan.
authors.forename: J B
authors.initials: JB
authors.lastname: Brown
authors.affiliation: Laboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University Graduate School of Medicine, Japan.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Abiko
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yoshioka
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Hamanishi
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Baba
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Koshiyama
authors.affiliation: Department of Obstetrics and Gynecology, Kinki University Faculty of Medicine, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mandai
authors.affiliation: The Center for Genomic Medicine, Kyoto University, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000032:analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use*; D059467:Transcriptome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D016190:Carboplatin; D017239:Paclitaxel
keywords: Gene expression profile; Ovarian cancer; Platinum; Prediction; Sensitivity; Taxane