paywalled - Gynecologic Oncology - Comparison of ERCC1/XPF genetic variation, mRNA and protein levels in women with advanced stage ovarian cancer treated with intraperitoneal platinum

ScienceDirect.com - Gynecologic Oncology - Comparison of ERCC1/XPF genetic variation, mRNA and protein levels in women with advanced stage ovarian cancer treated with intraperitoneal platinum

Abstract

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.

abstract: Balancing repair and tolerance of DNA damage caused by alkylating agents : Nature Reviews Cancer

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U of Toronto researcher discovers key protein involved in DNA repair Discovery gives insight into the way cells protect their own genetic material

Note: in research

"In a groundbreaking study, U of T researchers including Professors Daniel Durocher, Anne‐Claude Gingras and Frank Sicheri have uncovered a protein called OTUB1 that blocks DNA damage in the cell—a discovery that may lead to the development of strategies to improve some cancer therapies.
Lead author Durocher, a senior investigator at Mount Sinai Hospital’s Samuel Lunenfeld Research Institute and the Thomas Kierans Research Chair in Mechanisms of Cancer Development, as well as colleagues at U of T, Mount Sinai Hospital and the Keio University in Japan, have revealed pivotal new information on how cells regulate their genetic material. In addition, the discovery improves understanding of familial breast and ovarian cancer, as the research shows that OTUB1 inhibits the action of BRCA1, a DNA repair protein often mutated in these cancers...."cont'd