ERCC5 Is a Novel Biomarker of Ovarian Cancer Prognosis

To identify a biomarker of ovarian cancer response to chemotherapy. PATIENTS AND METHODS Study: participants had epithelial ovarian cancer treated with surgery followed by platinum-based chemotherapy. DNA and RNA were isolated from frozen tumors and normal DNA was isolated from matched peripheral bl...

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Bibliographic Details
Published in:	Journal of clinical oncology Vol. 26; no. 18; pp. 2952 - 2958
Main Authors:	WALSH, Christine S, OGAWA, Seishi, SANADA, Masashi, NANNYA, Yasuhito, SLAMON, Dennis J, KOEFFLER, H. Phillip, KARLAN, Beth Y, KARAHASHI, Hisae, SCALES, Daniel R, PAVELKA, James C, TRAN, Hang, MILLER, Carl W, KAWAMATA, Norihiko, GINTHER, Charles, DERING, Judy
Format:	Journal Article
Language:	English
Published:	Baltimore, MD American Society of Clinical Oncology 20-06-2008 Lippincott Williams & Wilkins
Subjects:	Adult Aged Aged, 80 and over Biological and medical sciences Biomarkers, Tumor - biosynthesis Biomarkers, Tumor - genetics Disease-Free Survival DNA, Neoplasm - analysis DNA-Binding Proteins - biosynthesis DNA-Binding Proteins - genetics Endonucleases - biosynthesis Endonucleases - genetics Female Female genital diseases Gene Expression Gynecology. Andrology. Obstetrics Humans Loss of Heterozygosity Medical sciences Middle Aged Nuclear Proteins - biosynthesis Nuclear Proteins - genetics Oligonucleotide Array Sequence Analysis Organoplatinum Compounds - therapeutic use Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Ovarian Neoplasms - metabolism Survival Rate Transcription Factors - biosynthesis Transcription Factors - genetics Tumors Ovarian diseases Cancerology Prognosis Ovary cancer ERCC5 gene Biological marker Malignant tumor Cancer Female genital diseases Repair gene
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Summary:	To identify a biomarker of ovarian cancer response to chemotherapy. PATIENTS AND METHODS Study: participants had epithelial ovarian cancer treated with surgery followed by platinum-based chemotherapy. DNA and RNA were isolated from frozen tumors and normal DNA was isolated from matched peripheral blood. A whole-genome loss of heterozygosity (LOH) analysis was performed using a high-density oligonucleotide array. Candidate genomic areas that predicted enhanced response to chemotherapy were identified with Cox proportional hazards methods. Gene expression analyses were performed through microarray experiments. Candidate genes were tested for independent effects on survival using Cox proportional hazards models, Kaplan-Meier survival curves, and the log-rank test. Using a whole-genome approach to study the molecular determinants of ovarian cancer response to platinum-based chemotherapy, we identified LOH of a 13q region to predict prolonged progression-free survival (PFS; hazard ratio, 0.23; P = .006). ERCC5 was identified as a candidate gene in this region because of its known function in the nucleotide excision repair pathway, the unique DNA repair pathway that removes platinum-DNA adducts. We found LOH of the ERCC5 gene locus and downregulation of ERCC5 gene expression to predict prolonged PFS. Integration of genomic and gene expression data shows a correlation between 13q LOH and ERCC5 gene downregulation. ERCC5 is a novel biomarker of ovarian cancer prognosis and a potential therapeutic target of ovarian cancer response to platinum chemotherapy.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0732-183X 1527-7755
DOI:	10.1200/JCO.2007.13.5806