alphaBeta-crystallin: A Novel Biomarker in Breast Cancer

乳腺癌是全世界妇女最常诊断的癌症，也是死亡的主要原因 在女人身上。虽然临床指标，如肿瘤大小，分级和腋窝淋巴结转移， 乳腺癌的有用的预后因素，迫切需要确定肿瘤生物标志物， 准确预测临床结果并指导个体患者的特定治疗。我们最近 证明了小的热休克蛋白α B-晶状体蛋白是一种新的致癌蛋白， 乳腺癌患者生存率低，与肿瘤分级、淋巴结状态、雌激素受体无关 和HER-2状态。我们还发现，α B-晶状体蛋白通常在基底样乳腺癌中表达， 肿瘤，一个新描述的临床侵袭性，雌激素受体阴性和ErbB2/HER-2- 阴性肿瘤，其发病机制知之甚少。此外，我们还证明了alphaB- 晶状体蛋白过表达对几种化疗药物诱导的乳腺癌细胞凋亡的保护作用 药物，但不是紫杉烷。因此，我们假设α B-晶状体蛋白是乳腺癌的一种新的生物标志物 独立预测（1）生存率差和（2）对许多化疗药物的耐药性，但不 紫杉烷类这一假设将在来自（1）-2000名妇女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 在淋巴结阳性患者中，紫杉醇作为阿霉素和环磷酰胺的辅助（术后）用药（目标1）; 和（2）在西北大学接受新辅助（术前）化疗的140例患者 (aim 2）。目的是：（1）研究α B-晶状体蛋白作为预后标志物的临床价值， 乳腺癌患者辅助化疗反应的预测因素;（2）检查临床价值 α B-晶状体蛋白作为乳腺癌新辅助化疗反应的预后标志物和预测因子 癌症患者。在这两个目标中，α B-晶状体蛋白的表达将通过免疫组织化学测定。 组织化学及其与其他肿瘤特征、存活率和化疗反应的关系将 在单变量和多变量分析中确定。相关性：这些研究将审查 α B-晶状体蛋白用于确定乳腺癌患者的预后和预测化疗反应。在 这样，这些研究可能有助于指导患者特异性化疗。

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.