Department of Surgery, Clinical Science Institute, National University of Ireland, Galway, Ireland.
Oncol Rep. 2012 Jul;28(1):365-9. doi: 10.3892/or.2012.1780. Epub 2012 Apr 23.
HER2/neu is associated with poorer clinical outcome in breast cancer. Expression patterns of co-localised cancer-associated genes at 17q12-21 were examined using RT-PCR. The study group consisted of a 96-patient cohort. Relative quantity of mRNA expression was calculated using the comparative cycle threshold method and Qbase software. Results were analysed to detect expression patterns among the genes, and to identify associations between expression levels and clinical data. Levels of HER2/neu correlated with those of GRB7 (r=0.551, p<0.001), RARA (r=0.391, p<0.001), RPL19 (r=0.549, p<0.001) and LASP1 (r=0.399, p<0.001). GRB7 was significantly inversely associated with improved DFS at 60 months (p=0.036). RARA levels were greater in HER2/neu-positive as opposed to HER2/neu-negative patients (p=0.021); levels were significantly higher in ER-positive patients, relative to those who were ER-negative (p=0.003). Levels of RPL19 were significantly higher in the HER2/neu-overexpressing (p=0.010) and luminal B subtypes (p=0.007). LASP1 levels were higher in those patients who had been classified clinically as HER2/neu-positive (p=0.004). This study reaffirms the correlation between HER2/neu and the co-localised LASP1 and GRB7; the latter target may hold additional significance in addition to being a surrogate marker for HER2/neu expression. The relationship identified between RARA and ER-positivity may herald an avenue for targeted therapy of these tumours.
HER2/neu 与乳腺癌的临床预后较差相关。使用 RT-PCR 检测了 17q12-21 处局部定位的癌症相关基因的表达模式。研究组由 96 例患者组成。使用比较循环阈值法和 Qbase 软件计算 mRNA 表达的相对数量。对结果进行分析,以检测基因之间的表达模式,并确定表达水平与临床数据之间的关联。HER2/neu 水平与 GRB7(r=0.551,p<0.001)、RARA(r=0.391,p<0.001)、RPL19(r=0.549,p<0.001)和 LASP1(r=0.399,p<0.001)的水平相关。GRB7 与 60 个月时的 DFS 显著呈负相关(p=0.036)。与 HER2/neu 阴性患者相比,HER2/neu 阳性患者的 RARA 水平更高(p=0.021);与 ER 阴性患者相比,ER 阳性患者的 RARA 水平更高(p=0.003)。在 HER2/neu 过表达(p=0.010)和管腔 B 型中,RPL19 的水平显著更高(p=0.007)。在临床分类为 HER2/neu 阳性的患者中,LASP1 水平更高(p=0.004)。本研究再次证实了 HER2/neu 与局部定位的 LASP1 和 GRB7 之间的相关性;后者可能除了是 HER2/neu 表达的替代标志物外,还具有额外的意义。确定的 RARA 与 ER 阳性之间的关系可能预示着针对这些肿瘤的靶向治疗途径。