alphaBeta-crystallin: A Novel Biomarker in Breast Cancer

αβ-晶状体蛋白：乳腺癌的新型生物标志物

基本信息

批准号：
7340131
负责人：
VINCENT L. CRYNS
金额：
$ 15.1万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-01-12 至 2008-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7340131
关键词：
Accounting Adjuvant Adjuvant Chemotherapy Aggressive behavior Apoptosis Axillary lymph node group Biological Markers Breast Breast Cancer Cell Breast Carcinoma Cancer Patient Cancer Prognosis Caspase Characteristics Clinical Clinical Data Clinical Trials Collaborations Crystallins Cytokeratin Disease-Free Survival Doxorubicin ERBB2 gene Enrollment Epithelial Cells Estrogen Receptor 2 Estrogen Receptor Status Estrogen receptor negative Gene Expression Genes Heat shock proteins Histocytochemistry Hospitals Immunohistochemistry Individual Journals Lead Link Malignant Neoplasms Mammary Neoplasms Modeling Molecular Multivariate Analysis National Surgical Adjuvant Breast and Bowel Project Nature Neoadjuvant Therapy Neoplasm Metastasis Oncogenic Operative Surgical Procedures Outcome Paclitaxel Pathogenesis Pathology Patients Pharmaceutical Preparations Population Positive Lymph Node Prognostic Factor Prognostic Marker Protein Overexpression Proteins Proto-Oncogene Protein c-kit Publishing Randomized Research Personnel Resistance Resources Sampling Taxane Compound Testing Tissue Microarray Tissues Treatment Protocols Universities Woman base cancer diagnosis caspase-3 chemotherapy cohort cyclophosphamide/doxorubicin protocol indexing lymph nodes malignant breast neoplasm mortality novel outcome forecast prognostic prospective response size tau Proteins taxane tumor

项目摘要

Breast cancer is the most frequently diagnosed cancer in women worldwide and is a major cause of mortality in women. Although clinical indices, such as tumor size, grade and axillary lymph node metastases, are useful prognostic factors in breast cancer, there is an urgent need to identify tumor biomarkers that more accurately predict clinical outcome and guide specific therapies for individual patients. We have recently demonstrated that the small heat shock protein alphaB-crystallin is a novel oncogenic protein that predicts poor survival in breast cancer patients independent of tumor grade, lymph node status, estrogen receptor and HER-2 status. We also showed that alphaB-crystallin is commonly expressed in basal-like breast tumors, a newly described subset of clinically aggressive, estrogen receptor-negative and ErbB2/HER-2- negative tumors whose pathogenesis is poorly understood. In addition, we have demonstrated that alphaB- crystallin overexpression protects breast cancer cells from apoptosis induced by several chemotherapy agents, but not taxanes. Hence, we hypothesize that alphaB-crystallin is a novel biomarker in breast cancer that independently predicts (1) poor survival and (2) resistance to many chemotherapy drugs but not taxanes. This hypothesis will be tested in well annotated tissue microarrays (TMAs) from (1) -2000 women enrolled in the NCI-supported NSABP B-28 cooperative clinical trial, which examined the benefit of adding adjuvant (post-surgery) taxol to doxorubicin and cyclosphosphamide in lymph node-positive patients (aim 1); and (2) -140 patients who received neoadjuvant (pre-surgery)chemotherapy at Northwestern University (aim 2). The aims are: (1) To examine the clinical value of alphaB-crystallin as a prognostic marker and predictor of adjuvant chemotherapy response in breast cancer patients; and (2) To examine the clinical value of alphaB-crystallin as a prognostic marker and predictor of neoadjuvant chemotherapy response in breast cancer patients. In both aims, the expression of alphaB-crystallin will be determined by immuno- histochemistry and its association with other tumor characteristics, survival and chemotherapy response will be determined in univariate and multivariate analyses. Relevance: These studies will examine the value of alphaB-crystallin to determine prognosis and predict chemotherapy response in breast cancer patients. In this way, these studies may help guide patient-specific chemotherapy treatment.

乳腺癌是全球女性最常被诊断出的癌症，是死亡率的主要原因在女性中。尽管临床指标，例如肿瘤大小，坡度和腋窝淋巴结转移，但在乳腺癌中有用的预后因素，迫切需要识别更多的肿瘤生物标志物准确预测临床结果并指导个别患者的特定疗法。我们最近有证明小热休克蛋白字母晶状体蛋白是一种新型的致癌蛋白，可以预测乳腺癌患者的生存率差，独立于肿瘤级，淋巴结状态，雌激素受体和HER-2身份。我们还表明，字母 - 晶状蛋白通常在基底乳房中表达肿瘤是一个新描述的临床攻击性，雌激素受体阴性和ERBB2/HER-2-的子集发病机理的阴性肿瘤知之甚少。此外，我们已经证明了字母结晶蛋白的过表达可保护乳腺癌细胞免受几种化疗诱导的凋亡代理人，但不是紫杉虫。因此，我们假设α-晶状体是乳腺癌的新生物标志物独立地预测（1）生存率不佳和（2）对许多化学疗法药物的抗性紫外线。该假设将在（1）-2000名女性的注释良好的组织微阵列（TMA）中进行检验参加了NCI支持的NSABP B-28合作临床试验，该试验检查了添加的好处淋巴结阳性患者中对阿霉素和环磷酰胺的辅助（手术后）紫杉醇（AIM 1）；（2）-140名在西北大学接受新辅助（手术前）化学疗法的患者（目标2）。目的是：（1）检查字母晶状体作为预后标记的临床价值和预测乳腺癌患者辅助化疗反应的因子；（2）检查临床价值 alphab-晶状蛋白作为预后标记和新辅助化疗反应的预测指标癌症患者。在这两个目的中，字母结晶蛋白的表达将由免疫 - 组织化学及其与其他肿瘤特征，生存和化学疗法反应的关联将会在单变量和多元分析中确定。相关性：这些研究将检查 α-结晶蛋白确定预后并预测乳腺癌患者的化学疗法反应。在这样，这些研究可能有助于指导患者特定的化学疗法治疗。