title: Integrated analysis of gene expression profiles associated with response of platinum/paclitaxel-based treatment in epithelial ovarian cancer.
abstract: OBJECTIVE
  This study aims to explore gene expression signatures and serum biomarkers to predict intrinsic chemoresistance in epithelial ovarian cancer (EOC).
  
  
  METHODS
  Gene expression profiling data of 322 high-grade EOC cases between 2009 and 2010 in The Cancer Genome Atlas project (TCGA) were used to develop and validate gene expression signatures that could discriminate different responses to first-line platinum/paclitaxel-based treatments. A gene regulation network was then built to further identify hub genes responsible for differential gene expression between the complete response (CR) group and the progressive disease (PD) group. Further, to find more robust serum biomarkers for clinical application, we integrated our gene signatures and gene signatures reported previously to identify secretory protein-encoding genes by searching the DAVID database. In the end, gene-drug interaction network was constructed by searching Comparative Toxicogenomics Database (CTD) and literature.
  
  
  RESULTS
  A 349-gene predictive model and an 18-gene model independent of key clinical features with high accuracy were developed for prediction of chemoresistance in EOC. Among them, ten important hub genes and six critical signaling pathways were identified to have important implications in chemotherapeutic response. Further, ten potential serum biomarkers were identified for predicting chemoresistance in EOC. Finally, we suggested some drugs for individualized treatment.
  
  
  CONCLUSIONS
  We have developed the predictive models and serum biomarkers for platinum/paclitaxel response and established the new approach to discover potential serum biomarkers from gene expression profiles. The potential drugs that target hub genes are also suggested.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research-Ministry of Education, Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xiao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Cao
authors.forename: Like
authors.initials: L
authors.lastname: Qu
authors.forename: Chengchao
authors.initials: C
authors.lastname: Shou
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000188:drug therapy; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage; D025341:Principal Component Analysis; D012372:ROC Curve; D043823:Taxoids / Q000008:administration & dosage; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel; D002945:Cisplatin