The prognostic value of MARCKS-like 1 in lymph node-negative breast cancer
The prognostic value of MARCKS-like 1 in lymph node-negative breast cancer
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DOI：
10.1007/s10549-012-2155-9
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发表时间：
2012-09-01
影响因子：
3.8
通讯作者：
Baak, Jan P. A.
中科院分区：
文献类型：
--
作者：
Jonsdottir, Kristin;Zhang, Hui;Baak, Jan P. A.
需要新的生物标志物来更正确地识别具有良好或不良预后的淋巴结阴性乳腺癌患者。豆蔻酰化富含丙氨酸的C激酶底物样-1（MARCKSL 1）是一种膜结合蛋白，与细胞铺展、整合素活化和胞吐作用有关。305例可手术的T1，2N 0 M0淋巴结阴性乳腺癌患者（中位随访时间121个月，范围10-178个月）通过免疫组织化学和定量实时PCR评估MARCKSL 1表达。采用Kaplan-Meier单因素生存分析和考克斯模型多因素生存分析，将结果与经典的生存分析指标（年龄、肿瘤直径、分级、雌激素受体和增殖）进行比较。47例患者（15%）发生远处转移。单因素和多因素分析显示，MARCKSL 1蛋白表达是最强的预测因子（P < 0.001，HR = 5.1，95%CI = 2.7-9.8）。在15年随访中，MARCKSL 1高表达患者（n = 23）的生存率为44%，而低表达患者的生存率为88%。福尔马林固定石蜡包埋组织中MARCKSL 1 mRNA表达也具有预后意义（P = 0.002，HR = 3.6，95%CI = 1.5-8.3）。然而，高和低的预后作用与蛋白表达相反，即，低表达（相对表达为千分之0.0264，n = 76）显示79%的存活率，而MARCKSL 1 mRNA高表达的那些为92%。以无远处转移生存期为终点的所有特征的多变量分析显示，MARCKSL 1蛋白和磷酸化组蛋白H3（PPH 3）的组合具有最强的独立预后价值。PPH 3高表达（千分之一日元13）和MARCKSL 1蛋白高表达的患者的生存率为45%，而MARCKSL 1蛋白低表达和PPH 3高表达（千分之一日元13）的患者的生存率为78%。总之，MARCKSL 1在淋巴结阴性乳腺癌患者中具有很强的预后价值，特别是在那些高增殖的患者中。
There is a need for new biomarkers to more correctly identify node-negative breast cancer patients with a good or bad prognosis. Myristoylated alanine-rich C kinase substrate like-1 (MARCKSL1) is a membrane-bound protein that is associated with cell spreading, integrin activation and exocytosis. Three hundred and five operable T1,2N0M0 lymph node-negative breast cancer patients (median follow-up time 121 months, range 10-178 months) were evaluated for MARCKSL1 expression by immunohistochemistry and quantitative real-time PCR. The results were compared with classical prognosticators (age, tumor diameter, grade, estrogen receptor, and proliferation), using single (Kaplan-Meier) and multivariate survival analysis (Cox model). Forty-seven patients (15 %) developed distant metastases. With single and multivariate analysis of all features, MARCKSL1 protein expression was the strongest prognosticator (P < 0.001, HR = 5.1, 95 % CI = 2.7-9.8). Patients with high MARCKSL1 expression (n = 23) showed a 44 % survival versus 88 % in patients with low expression at 15-year follow-up. mRNA expression of MARCKSL1 in formalin fixed paraffin-embedded tissue was also prognostic (P = 0.002, HR = 3.6, 95 % CI = 1.5-8.3). However, the prognostic effect of high and low was opposite from the protein expression, i.e., low expression (relative expression a parts per thousand currency sign 0.0264, n = 76) showed a 79 % survival versus 92 % in those with high expression of MARCKSL1 mRNA. Multivariate analysis of all features with distant metastases free survival as the end-point showed that the combination of MARCKSL1 protein and phosphohistone H3 (PPH3) has the strongest independent prognostic value. Patients with high expression (a parts per thousand yen13) of PPH3 and high MARCKSL1 protein had 45 % survival versus 78 % survival for patients with low MARCKSL1 protein expression and high expression (a parts per thousand yen13) of PPH3. In conclusion, MARCKSL1 has strong prognostic value in lymph node-negative breast cancer patients, especially in those with high proliferation.