title: Molecular biomarkers of residual disease after surgical debulking of high-grade serous ovarian cancer.
abstract: OBJECTIVE
  Residual disease following primary cytoreduction is associated with adverse overall survival in patients with epithelial ovarian cancer. Accurate identification of patients at high risk of residual disease has been elusive, lacking external validity and prompting many to undergo unnecessary surgical exploration. Our goal was to identify and validate molecular markers associated with high rates of residual disease.
  
  
  METHODS
  We interrogated two publicly available datasets from chemonaïve primary high-grade serous ovarian tumors for genes overexpressed in patients with residual disease and significant at a 10% false discovery rate (FDR) in both datasets. We selected genes with wide dynamic range for validation in an independent cohort using quantitative RT-PCR to assay gene expression, followed by blinded prediction of a patient subset at high risk for residual disease. Predictive success was evaluated using a one-sided Fisher exact test.
  
  
  RESULTS
  Forty-seven probe sets met the 10% FDR criterion in both datasets. These included FABP4 and ADH1B, which tracked tightly, showed dynamic ranges >16-fold and had high expression levels associated with increased incidence of residual disease. In the validation cohort (n = 139), FABP4 and ADH1B were again highly correlated. Using the top quartile of FABP4 PCR values as a prespecified threshold, we found 30 of 35 cases of residual disease in the predicted high-risk group (positive predictive value = 86%) and 54 of 104 among the remaining patients (P = 0.0002; OR, 5.5).
  
  
  CONCLUSIONS
  High FABP4 and ADH1B expression is associated with significantly higher risk of residual disease in high-grade serous ovarian cancer. Patients with high tumoral levels of these genes may be candidates for neoadjuvant chemotherapy.
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Tucker
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Kshipra
authors.initials: K
authors.lastname: Gharpure
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Shelley M
authors.initials: SM
authors.lastname: Herbrich
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Unruh
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Alpa M
authors.initials: AM
authors.lastname: Nick
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Erin K
authors.initials: EK
authors.lastname: Crane
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Jamie
authors.initials: J
authors.lastname: Guenthoer
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Dalton
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Sherry Y
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Rajesha
authors.initials: R
authors.lastname: Rupaimoole
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, WashingtonAuthors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Bulent
authors.initials: B
authors.lastname: Ozpolat
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ivan
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Baggerly
authors.affiliation: Authors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, WashingtonAuthors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, WashingtonAuthors' Affiliations: Departments of Bioinformatics and Computational Biology, Gynecologic Oncology and Reproductive Medicine, Experimental Therapeutics, Cancer Biology, and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Fred Hutchinson Cancer Research Center, Seattle, Washington asood@mdanderson.org.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D065426:Cytoreduction Surgical Procedures; D050556:Fatty Acid-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060787:Neoplasm Grading; D018365:Neoplasm, Residual / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D012333:RNA, Messenger; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase
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