title: Clinical and Emergent Biomarkers and Their Relationship to the Prognosis of Ovarian Cancer.
abstract: OBJECTIVE
  Ovarian cancer is the most lethal gynecological malignancy, but information relevant to prognosis and outcomes remain unknown. Here, we used statistical methods to focus specifically on interactions between candidate prognostic variables.
  
  
  RESULTS
  Univariate, multivariate, and elastic net modeling of 42 variables were applied to a cohort of 542 ovarian cancer patients with 393 episodes of cancer recurrence/death. In univariate analyses, overexpression of TFF3, MDM2, and p53 were associated with improved recurrence-free survival. In multivariate analyses adjusted for age, histology, stage, grade, ascites, and residual disease, overexpression of PR appeared to provide a protective effect [hazard ratio for >50% of cells positive, 0.64 (95% confidence interval 0.44-0.94) compared to <1%], and TFF3 showed a nonlinear association. Importantly, we observed no interactions among variables. However, patients with tumors with moderate TFF3 expression were at a marginally increased risk of recurrence, and patients with tumors with high expression were at a similar to slightly lower risk, compared to those with tumors with no TFF3 expression.
  
  
  CONCLUSIONS
  Although no interactions among variables were observed, this study provides important precedent for seeking interactions between clinical and tumor variables in future studies.
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, Minn., USA.
authors.forename: Aminah
authors.initials: A
authors.lastname: Jatoi
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Kieran M
authors.initials: KM
authors.lastname: Hawthorne
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Block
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Larson
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
mesh_terms: D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000737:chemistry*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000473:pathology*; D010455:Peptides / Q000032:analysis*; D011379:Prognosis; D016016:Proportional Hazards Models; D065840:Protective Factors; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis*; D011980:Receptors, Progesterone; D012044:Regression Analysis; D012307:Risk Factors; D013223:Statistics as Topic; D000071165:Trefoil Factor-3; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D010455:Peptides; D011980:Receptors, Progesterone; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2