Objective: Approximately 20% of patients receiving platinum-based chemotherapy for epithelial ovarian cancer (EOC) are refractory or develop early recurrence. Identifying these patients early could reduce treatment-associated morbidity and allow quicker transfer to more effective therapies. Much attention has focused on ERCC1 as a potential predictor of response to therapy because of its essential role in the repair of platinum-induced DNA damage. The purpose of this study was to accurately measure protein levels of ERCC1 and its essential binding partner XPF from patients with EOC treated with platinum-based therapy and determine if protein levels correlate with mRNA levels, patient genotypes or clinical outcomes. Methods: ERCC1 and XPF mRNA and protein levels were measured in frozen EOC specimens from 41 patients receiving intraperitoneal platinum-based chemotherapy using reverse transcription polymerase chain reaction and western blots. Genotypes of common nucleotide polymorphisms were also analyzed. Patient outcomes included progression free (PFS) and overall survival (OS). Results: Expression of ERCC1 and XPF were tightly correlated with one another at both the mRNA and protein level. However, the mRNA and protein levels of ERCC1 were not positively correlated. Likewise, none of the SNPs analyzed correlated with ERCC1 or XPF protein levels. There was an inverse correlation between mRNA levels and patient outcomes. Conclusion: Neither genotype nor mRNA levels are predictive of protein expression. Despite this, low ERCC1 mRNA significantly correlated with improved PFS and OS.
Bibliographical noteFunding Information:
N.B. and L.J.N. were supported by the National Institutes of Health ES016114 and ES016114-03S1 . M.S., T.K. and J.D. were supported by the University of Pittsburgh Medical Center Magee Womens Hospital . K.D. and C.T. were supported by the Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- DNA repair
- Platinum therapy
- Single nucleotide polymorphism