Gene expression determinants of ovarian cancer platinum-response in older women.

22059 Background: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, and more than half of new ovarian cancer cases arise in women over age 65. Although older women with EOC have poorer overall prognosis compared to younger women, the exact molecular basis to this difference remains unclear. The goal of this study is to improve our understanding of the molecular underpinnings of advanced stage EOC in older women and identify genes associated with chemo-response in older women such that therapy may be tailored to individual patients. METHODS: We performed Affymetrix microarray gene expression analysis on 122 primary advanced stage epithelial ovarian cancers resected from 73 younger (<65 years) and 49 older (>65 years) women. For each age group, gene expression data was compared using Significance Analysis of Microarrays (SAM), between patients who demonstrated a complete-response (>65 years, n=38; <65 years, n=48) and incomplete-response (>65 years, n=11; <65 years, n=25) to primary platinum-based chemotherapy. Differential expression was determined by two class unpaired t-tests (false discovery rate, 0%), and results ranked according to d score. RESULTS: We identified 317 genes associated with platinum-response in cancers from younger women, and 264 genes associated with platinum-response in cancers from older women. Six genes (JRKL, LRP8, OVOL2, PKP4, SRD5A1, TMEM1) demonstrated differential expression associated with platinum-response in cancers from both age groups. Genes associated with platinum-response in older, but not younger, women have functional links to apoptosis regulation, programmed cell death, and cell growth. In contrast, genes associated with platinum-response in younger women have functional links to DNA repair. CONCLUSIONS: We have identified genes associated with response to platinum-based therapy in younger and older women with EOC. Our data provides insights into biologic functions that may underlie differences in chemo-responsiveness in older versus younger women with EOC. Identifying the molecular underpinnings that drive response to chemotherapy in older women may enable clinicians to tailor therapy and identify potential novel therapeutic targets. No significant financial relationships to disclose.

Duke Scholars

Author Andrew Berchuck Obstetrics and Gynecology, Gynecologic Oncology