title: Predictive value of ATP7b, BRCA1, BRCA2, PARP1, UIMC1 (RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) genes in patients with epithelial ovarian cancer who received platinum-taxane first-line therapy.
abstract: To evaluate the predictive value of genes involved in resistance to platinum-taxane chemotherapy in patients with epithelial ovarian cancer (EOC). Microdissected formalin-fixed tumoral samples from 187 EOC patients' primary tumors (90 and 97 samples from matched patients in the experimental and validation sets, respectively) were analyzed. All specimens were analyzed for ATP7b, BRCA1, BRCA2, PARP1, UIMC1(RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) mRNA expression by quantitative real-time PCR. Most of the patients (172 out of 187) received front-line carboplatin-paclitaxel regimen. Expression levels were correlated with overall (OS) and progression-free (PFS) survival by multivariate analysis. Patients with high TXN and THBS1 expression presented longer PFS (P=0.001 and P<0.001, respectively) and OS (P=0.024 and P<0.001, respectively). High TXR1 expression was associated with decreased PFS (P<0.001) and OS (P<0.001). Multivariate analysis demonstrated that high PRR13/low THBS1 expression was an independent factor for decreased PFS (hazards ratio: 1.94; 95% confidence interval (CI): 1.48-2.92; P=0.008) and OS (hazard ratio: 3.89; 95% CI: 2.16-6.87; P<0.001), whereas low TXN expression was correlated with decreased PFS (hazard ratio: 1.44; 95% CI: 1.05-2.84; P=0.043) and OS (hazard ratio: 2.38; 95% CI: 1.78-2.77; P=0.009). These findings indicate that PRR13/THBS1 and TXN expression could be used for the prediction of resistance to treatment of EOC patients and, therefore, merit to be further evaluated.
authors: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors: S
authors: S
authors: Pontikakis
authors: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors: C
authors: C
authors: Papadaki
authors: Department of Pathology, Heraklion, Greece.
authors: M
authors: M
authors: Tzardi
authors: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors: M
authors: M
authors: Trypaki
authors: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors: M
authors: M
authors: Sfakianaki
authors: Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Greece.
authors: F
authors: F
authors: Koinis
authors: Department of Pathology, Heraklion, Greece.
authors: E
authors: E
authors: Lagoudaki
authors: Department of Pathology, Venizelion General Hospital, Heraklion, Greece.
authors: L
authors: L
authors: Giannikaki
authors: Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Greece.
authors: A
authors: A
authors: Kalykaki
authors: Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Greece.
authors: E
authors: E
authors: Kontopodis
authors: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors: Z
authors: Z
authors: Saridaki
authors: Department of Medical Oncology, Elena Venizelou Hospital, Athens, Greece.
authors: N
authors: N
authors: Malamos
authors: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Crete, Greece.|Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Greece.
authors: V
authors: V
authors: Georgoulias
authors: Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Crete, Greece.|Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Greece.
authors: J
authors: J
authors: Souglakos
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use; D000077216:Carcinoma, Ovarian Epithelial; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use; D013879:Thioredoxins / Q000235:genetics*; D019700:Thrombospondin 1 / Q000235:genetics*
chemical_list: D001952:Bridged-Ring Compounds; C513606:PRR13 protein, human; D012097:Repressor Proteins; C491203:TXN protein, human; D043823:Taxoids; D019700:Thrombospondin 1; C000611726:thrombospondin-1, human; C080625:taxane; D013879:Thioredoxins; D016190:Carboplatin