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

• 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
• 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

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.

乳腺癌是全世界女性最常被诊断出的癌症，也是导致死亡的主要原因。 在女人身上。尽管临床指标，如肿瘤大小，分级和腋窝淋巴结转移， 乳腺癌中有用的预后因素，迫切需要确定更多的肿瘤生物标志物 准确预测临床结果，指导个别患者的具体治疗。我们最近做了 证明小分子热休克蛋白αB-晶体蛋白是一种新的致癌蛋白，可以预测 乳腺癌患者的低生存率与肿瘤分级、淋巴结状况、雌激素受体无关 和她的2号身份。我们还发现α-晶体蛋白在基底样乳房中普遍表达。 肿瘤，一种新发现的临床侵袭性、雌激素受体阴性和ErbB2/HER-2- 阴性肿瘤，其发病机制尚不清楚。此外，我们还证明了字母b- 晶状体蛋白过表达对多种化疗诱导的乳腺癌细胞凋亡的保护作用 代理商，但不是紫杉烷。因此，我们假设α-晶体蛋白是乳腺癌的一种新的生物标志物。 这独立地预测(1)较差的存活率和(2)对许多化疗药物的耐药性，但不是 紫杉烷。这一假设将在(1)-2000名女性的组织微阵列(TMA)中得到验证 登记参加NCI支持的NSABP B-28合作临床试验，该试验检查了添加 淋巴结阳性患者(术后)紫杉醇对阿霉素和环磷酰胺的辅助作用(目标1)； 以及(2)--在西北大学接受新辅助(术前)化疗的140名患者 (目标2)。其目的是：(1)探讨α-晶体蛋白作为预后标志物的临床应用价值。 乳腺癌患者辅助化疗疗效的预测指标；(2)临床应用价值 α-晶体蛋白作为乳腺癌新辅助化疗疗效的预后标志物和预测因子 癌症患者。在这两个目标中，α-晶体蛋白的表达将通过免疫- 组织化学及其与其他肿瘤特征、生存期和化疗反应的关系 在单变量和多变量分析中确定。相关性：这些研究将检验 α-晶体蛋白在判断乳腺癌患者预后和预测化疗疗效中的作用。在……里面 通过这种方式，这些研究可能有助于指导针对患者的化疗治疗。