Université de Franche-Comté, UFR Sciences et Techniques, Besançon, France.
Br J Cancer. 2010 Mar 16;102(6):1024-31. doi: 10.1038/sj.bjc.6605568. Epub 2010 Mar 2.
This study evaluates the relation of the early oestrogen-regulated gene gabarapl1 to cellular growth and its prognostic significance in breast adenocarcinoma.
First, the relation between GABARAPL1 expression and MCF-7 growth rate was analysed. Thereafter, by performing macroarray and reverse transcriptase quantitative-polymerase chain reaction (RT-qPCR) experiments, gabarapl1 expression was quantified in several histological breast tumour types and in a retrospective cohort of 265 breast cancers.
GABARAPL1 overexpression inhibited MCF-7 growth rate and gabarapl1 expression was downregulated in breast tumours. Gabarapl1 mRNA levels were found to be significantly lower in tumours presenting a high histological grade, with a lymph node-positive (pN+) and oestrogen and/or progesterone receptor-negative status. In univariate analysis, high gabarapl1 levels were associated with a lower risk of metastasis in all patients (hazard ratio (HR) 4.96), as well as in pN+ patients (HR 14.96). In multivariate analysis, gabarapl1 expression remained significant in all patients (HR 3.63), as well as in pN+ patients (HR 5.65). In univariate or multivariate analysis, gabarapl1 expression did not disclose any difference in metastasis risk in lymph node-negative patients.
Our data show for the first time that the level of gabarapl1 mRNA expression in breast tumours is a good indicator of the risk of recurrence, specifically in pN+ patients.
本研究评估了早期雌激素调节基因 gabarapl1 与细胞生长的关系及其在乳腺腺癌中的预后意义。
首先,分析 GABARAPL1 表达与 MCF-7 生长速度的关系。然后,通过进行宏阵列和逆转录定量聚合酶链反应 (RT-qPCR) 实验,在几种组织学类型的乳腺肿瘤和 265 例乳腺癌的回顾性队列中定量分析了 gabarapl1 的表达。
GABARAPL1 过表达抑制 MCF-7 生长速度,gabarapl1 在乳腺肿瘤中表达下调。发现高组织学分级、淋巴结阳性 (pN+)、雌激素和/或孕激素受体阴性的肿瘤中 gabarapl1 mRNA 水平显著降低。在单因素分析中,高 gabarapl1 水平与所有患者(危险比 (HR) 4.96)以及 pN+患者(HR 14.96)的转移风险降低相关。在多因素分析中,gabarapl1 表达在所有患者(HR 3.63)以及 pN+患者(HR 5.65)中仍然显著。在单因素或多因素分析中,gabarapl1 表达在淋巴结阴性患者的转移风险中未显示出任何差异。
我们的数据首次表明,乳腺肿瘤中 gabarapl1 mRNA 表达水平是复发风险的良好指标,特别是在 pN+患者中。