title: Prediction of chemo-response in serous ovarian cancer.
abstract: Nearly one-third of serous ovarian cancer (OVCA) patients will not respond to initial treatment with surgery and chemotherapy and die within one year of diagnosis. If patients who are unlikely to respond to current standard therapy can be identified up front, enhanced tumor analyses and treatment regimens could potentially be offered. Using the Cancer Genome Atlas (TCGA) serous OVCA database, we previously identified a robust molecular signature of 422-genes associated with chemo-response. Our objective was to test whether this signature is an accurate and sensitive predictor of chemo-response in serous OVCA.
  
  
  
  We first constructed prediction models to predict chemo-response using our previously described 422-gene signature that was associated with response to treatment in serous OVCA. Performance of all prediction models were measured with area under the curves (AUCs, a measure of the model's accuracy) and their respective confidence intervals (CIs). To optimize the prediction process, we determined which elements of the signature most contributed to chemo-response prediction. All prediction models were replicated and validated using six publicly available independent gene expression datasets.
  
  
  
  The 422-gene signature prediction models predicted chemo-response with AUCs of ~70 %. Optimization of prediction models identified the 34 most important genes in chemo-response prediction. These 34-gene models had improved performance, with AUCs approaching 80 %. Both 422-gene and 34-gene prediction models were replicated and validated in six independent datasets.
  
  
  
  These prediction models serve as the foundation for the future development and implementation of a diagnostic tool to predict response to chemotherapy for serous OVCA patients.
authors.affiliation: Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USA. jesus-gonzalezbosquet@uiowa.edu.
authors.forename: Jesus
authors.initials: J
authors.lastname: Gonzalez Bosquet
authors.affiliation: Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USA.
authors.forename: Andreea M
authors.initials: AM
authors.lastname: Newtson
authors.affiliation: Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USA.
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Chung
authors.affiliation: Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USA.
authors.forename: Kristina W
authors.initials: KW
authors.lastname: Thiel
authors.affiliation: Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.|Biostatistics, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Ginader
authors.affiliation: Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USA.|Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Goodheart
authors.affiliation: Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USA.|Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Leslie
authors.affiliation: Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.|Biostatistics, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Smith
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D057285:Precision Medicine; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Chemo-response; Data integration; Individualized treatment; Ovarian cancer; Prediction model