Disciplina de Oncologia, Departamento de Radiologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Breast Cancer Res Treat. 2011 Feb;126(1):1-14. doi: 10.1007/s10549-010-0867-2. Epub 2010 Apr 6.
An increasing number of studies have shown altered expression of secreted protein acidic and rich in cysteine (SPARC) and N-myc down-regulated gene (NDRG1) in several malignancies, including breast carcinoma; however, the role of these potential biomarkers in tumor development and progression is controversial. In this study, NDRG1 and SPARC protein expression was evaluated by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with 10 years of follow-up. NDRG1 and SPARC protein expression was determined in 596 patients along with other prognostic markers, such as ER, PR, and HER2. The status of NDRG1 and SPARC protein expression was correlated with prognostic variables and patient clinical outcome. Immunostaining revealed that 272 of the 596 cases (45.6%) were positive for NDRG1 and 431 (72.3%) were positive for SPARC. Statistically significant differences were found between the presence of SPARC and NDRG1 protein expression and standard clinicopathological variables. Kaplan-Meier analysis showed that NDRG1 positivity was directly associated with shorter disease-free survival (DFS, P < 0.001) and overall survival (OS, P < 0.001). In contrast, patients expressing low levels of SPARC protein had worse DFS (P = 0.001) and OS (P = 0.001) compared to those expressing high levels. Combined analysis of the two markers indicated that DFS (P < 0.001) and OS rates (P < 0.001) were lowest for patients with NDRG1-positive and SPARC-negative tumors. Furthermore, NDRG1 over-expression and SPARC down-regulation correlated with poor prognosis in patients with luminal A or triple-negative subtype breast cancer. On multivariate analysis using a Cox proportional hazards model, NDRG1 and SPARC protein expression were independent prognostic factors for both DFS and OS of breast cancer patients. These data indicate that NDRG1 over-expression and SPARC down-regulation could play important roles in breast cancer progression and serve as useful biomarkers to better define breast cancer prognosis.
越来越多的研究表明，在包括乳腺癌在内的几种恶性肿瘤中，分泌型酸性富含半胱氨酸蛋白（SPARC）和 N- myc 下调基因 1（NDRG1）的表达发生了改变；然而，这些潜在的生物标志物在肿瘤发生和发展中的作用仍存在争议。在这项研究中，通过免疫组织化学方法，在含有 10 年随访的乳腺癌标本的组织微阵列上评估了 NDRG1 和 SPARC 蛋白的表达。在 596 例患者中，与其他预后标志物（如 ER、PR 和 HER2）一起确定了 NDRG1 和 SPARC 蛋白的表达情况。SPARC 和 NDRG1 蛋白表达的状态与预后变量和患者临床结局相关。免疫染色显示，596 例病例中的 272 例（45.6%）为 NDRG1 阳性，431 例（72.3%）为 SPARC 阳性。SPARC 和 NDRG1 蛋白表达与标准临床病理变量之间存在统计学显著差异。Kaplan-Meier 分析显示，NDRG1 阳性与无病生存期（DFS，P < 0.001）和总生存期（OS，P < 0.001）较短直接相关。相比之下，表达低水平 SPARC 蛋白的患者 DFS（P = 0.001）和 OS（P = 0.001）更差。对这两个标志物的联合分析表明，对于 NDRG1 阳性和 SPARC 阴性肿瘤的患者，DFS（P < 0.001）和 OS 率（P < 0.001）最低。此外，NDRG1 过表达和 SPARC 下调与 luminal A 或三阴性乳腺癌患者的不良预后相关。在使用 Cox 比例风险模型的多变量分析中，NDRG1 和 SPARC 蛋白表达是乳腺癌患者 DFS 和 OS 的独立预后因素。这些数据表明，NDRG1 过表达和 SPARC 下调可能在乳腺癌的进展中发挥重要作用，并可作为更好地定义乳腺癌预后的有用生物标志物。
