Improving genomic prediction models in breast cancer

改进乳腺癌基因组预测模型

• 批准号: 6945375
• 负责人: JOHN A. OLSON
• 金额: $ 13.86万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-02 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6945375
• 关键词: biomarker; biopsy; breast neoplasm /cancer diagnosis; clinical research; diagnosis design /evaluation; estrogen receptors; female; gene expression; human subject; ischemia; lymph nodes; menopause; neoplasm /cancer relapse /recurrence; outcomes research; patient oriented research; postmenopause; women' s health

DESCRIPTION (provided by applicant): Breast cancer is a heterogeneous disease with variable biology and often-unpredictable clinical outcomes. Genomic technologies have shown promise to better discriminate between patients of similar clinicopathologic stage and in some cases predict clinical outcomes. We and others have published studies of array-based predictive modeling of breast cancer outcomes, including ER status, lymph node status, and disease recurrence. While these initial studies raise hope for genomic-based personalized outcome predictions, significant questions must be answered before expression array-based prognostics can be incorporated into clinical medicine. For example, does normal variation in breast tumor gene expression affect expression-based outcome predictions? Our recent data suggest that replicate samples of similar tumor taken from the same breast tumor at two different times show consistent patterns of global gene expression. On the other hand, replicate tumor specimens of different cellular heterogeneity or those subjected to different periods of ischemia have significant differences in global gene expression as well. Importantly, this variation, which can reasonably be expected to occur under routine clinical conditions, gives different model predictions of outcome in some cases. We now believe that understanding variation in gene expression and incorporating knowledge about this variation in genomic-based models may provide useful information to improve the accuracy of these models. In this proposal, we will test this hypothesis that ascertainment of biologic and process variability in breast cancer gene expression will improve the ability of gene expression-based models to predict breast cancer outcomes, including ER status, metastasis to axillary lymph nodes and disease recurrence. Specifically, we aim to: Specific Aim 1: To determine whether gene expression data from core biopsy specimens of different cellular content give similar predictions in a gene expression-based predictive model of ER status, axillary lymph node metastasis and recurrence in breast cancer. Specific Aim 2: To identify changes in breast tumor gene expression with tissue ischemia and determine the impact of these changes on gene expression-based predictive models of ER status, axillary lymph node status and recurrence in breast cancer. Specific Aim 3: To measure variability in gene expression in T1N0M0 hormone receptor positive breast cancer in pre- and postmenopausal women and ascertain whether this variability changes expression-based model predictions of ER status, axillary lymph node status and recurrence in breast cancer.

描述（由申请人提供）：乳腺癌是一种异质性疾病，具有可变的生物学特性和常常不可预测的临床结果。基因组技术已显示出有望更好地区分相似临床病理阶段的患者，并在某些情况下预测临床结果。我们和其他人发表了基于阵列的乳腺癌结果预测模型的研究，包括 ER 状态、淋巴结状态和疾病复发。虽然这些初步研究为基于基因组的个性化结果预测带来了希望，但在将基于表达阵列的预后纳入临床医学之前，必须回答重要的问题。例如，乳腺肿瘤基因表达的正常变化是否会影响基于表达的结果预测？我们最近的数据表明，在两个不同时间取自同一乳腺肿瘤的相似肿瘤的复制样本显示出一致的整体基因表达模式。另一方面，不同细胞异质性或经历不同缺血时期的复制肿瘤标本的整体基因表达也存在显着差异。重要的是，这种变化可以合理地预期在常规临床条件下会发生，但在某些情况下给出了不同的结果模型预测。我们现在相信，了解基因表达的变异并将有关这种变异的知识纳入基于基因组的模型中可能会提供有用的信息，以提高这些模型的准确性。在本提案中，我们将测试这一假设，即确定乳腺癌基因表达的生物学和过程变异性将提高基于基因表达的模型预测乳腺癌结果的能力，包括 ER 状态、腋窝淋巴结转移和疾病复发。具体来说，我们的目标是： 具体目标 1：确定不同细胞含量的核心活检标本的基因表达数据是否在基于基因表达的乳腺癌 ER 状态、腋窝淋巴结转移和复发的预测模型中给出相似的预测。 具体目标 2：确定乳腺肿瘤基因表达随组织缺血的变化，并确定这些变化对基于基因表达的 ER 状态、腋窝淋巴结状态和乳腺癌复发预测模型的影响。 具体目标 3：测量绝经前和绝经后女性 T1N0M0 激素受体阳性乳腺癌基因表达的变异性，并确定这种变异性是否会改变基于表达的模型对 ER 状态、腋窝淋巴结状态和乳腺癌复发的预测。

项目成果

A balanced level of profilin-1 promotes stemness and tumor-initiating potential of breast cancer cells.

平衡水平的 profilin-1 可促进乳腺癌细胞的干细胞性和肿瘤启动潜力。

• 发表时间: 2017
• 作者: Jiang, Chang;Ding, Zhijie;Joy, Marion;Chakraborty, Souvik;Kim, Su Hyeong;Bottcher, Ralph;Condeelis, John;Singh, Shivendra;Roy, Partha
• 通讯作者: Roy, Partha