Gene expression profiles to predict ovarian cancer chemo-response in the elderly

描述（由申请人提供）：上皮性卵巢癌是最致命的妇科恶性肿瘤，超过一半的卵巢癌新病例发生在65岁以上的女性中。尽管与年轻女性相比，患有卵巢癌的老年女性总体预后较差，但这种差异的确切分子基础尚不清楚。我们分析了76例晚期浆液性卵巢癌的初步微阵列数据，表明有可能确定老年和年轻女性上皮性卵巢癌差异的离散全局基因表达模式。此外，我们的初步研究结果表明，它可能预测老年和年轻妇女对化疗的反应。当前提案的目标是扩展我们的初步发现，以提高对老年妇女晚期上皮性卵巢癌分子基础的理解，并确定可能预测化疗反应的基因表达谱，从而使未来的治疗可能针对个体患者进行定制。我们计划对来自老年和年轻女性的64例晚期浆液性卵巢癌进行微阵列基因表达分析。这项分析的数据将与先前在初步研究中收集的76个样本的数据相结合，总共提供140个样本（70个来自老年妇女，70个来自年轻妇女）。将比较老年（65岁以上）和年轻（65岁以下）女性癌症患者的基因表达模式，以确定可能导致两组患者生存率差异的基因。此外，对于两个年龄组，将比较来自对辅助铂/紫杉烷化疗表现出完全反应和不完全反应的患者的癌症的基因表达模式。贝叶斯回归分析将用于开发预测模型，该模型将在留一交叉验证研究中进行测试。将比较预测每个年龄组（老年人和年轻人）反应的概况。预测老年妇女化疗反应的基因谱特征将促进基因表达谱导向疗法的发展，这将有助于老年人口的临床决策。因此，预测谱将使治疗方法适合老年患者，从而提高治疗效果和反应率，减少不必要的毒性，重要的是，提高老年卵巢癌患者的生活质量。

DESCRIPTION (provided by applicant): Epithelial ovarian cancer is the most lethal gynecologic malignancy, and more than half of all new cases of ovarian cancer arise in women over age 65. Although elderly women with ovarian cancer have been shown to have a poorer overall prognosis compared to younger women, the exact molecular basis of this difference remains unclear. We have preliminary microarray data from analysis of 76 advanced serous ovarian cancers suggesting that it may be possible to identify discrete global gene expression patterns that underlie differences in epithelial ovarian cancer between elderly and younger women. Further our preliminary findings suggest that it may be possible to predict response to chemotherapy in elderly and younger women. The goal of the current proposal is to extend our preliminary findings to improve understanding of the molecular underpinnings of advanced stage epithelial ovarian cancer in elderly women and to identify gene expression profiles that may predict chemo-response, such that future therapy may be tailored to individual patients. We plan to perform microarray gene expression analysis of 64 advanced stage serous ovarian cancers from elderly and younger women. Data from this analysis will be combined with data from 76 samples previously arrayed in preliminary studies to provide a total of 140 samples (70 from elderly women and 70 from younger women). Gene expression patterns will be compared between cancers from elderly (>65 yrs age) and younger (<65 yrs age) women to identify genes that may underlie the difference survival between the 2 groups. Additionally, for both age groups, gene expression patterns will be compared between cancers from patients that demonstrated a complete- versus an incomplete-response to adjuvant platinum/taxane chemotherapy. Bayesian regression analysis will be used to develop predictive models which will be tested in leave-one-out cross validation studies. The profiles that predict response in each age group (elderly and younger) will be compared. Characterization of gene profiles that predict chemo- response in elderly women will facilitate the development of gene expression profile-directed therapies that will aid clinical-decision making in the aging population. As such, predictive profiles will enable therapies to be tailored to elderly patients, and thus improve treatment efficacy and response rates, decrease unnecessary toxicities, and importantly, enhance quality of life for aging patients with ovarian cancer.