Prediction of prognosis of estrogen receptor-positive breast cancer with combination of selected estrogen-regulated genes
Prediction of prognosis of estrogen receptor-positive breast cancer with combination of selected estrogen-regulated genes
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DOI：
10.1111/j.1349-7006.2004.tb03239.x
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发表时间：
2004-06-01
期刊：
影响因子：
5.7
通讯作者：
Hayashi, S
中科院分区：
文献类型：
--
作者：
Yoshida, N;Omoto, Y;Hayashi, S
雌激素受体（ER）阳性乳腺癌是乳腺癌的一个独特的亚群，对内分泌治疗表现出高反应率。然而，并不是所有的ER阳性患者对治疗都有反应，并且基于雌激素信号传导的生理学的ER阳性患者的亚组预期可用于预测预后。这项研究表明，选定的雌激素调节基因（ERG）是有用的，在识别ER阳性乳腺癌患者中的预后不良人群。首先，11个ERG的表达水平，选择基于我们早期的微阵列研究在培养细胞，通过实时逆转录-PCR在14 ER阳性的人乳腺癌组织进行了分析。聚类分析将患者明显分为两组。然后，我们用免疫组织化学方法检测了62例ER阳性患者中两种代表性ERG的表达水平，即组蛋白脱乙酰酶6（HDAC 6）和胰岛素样生长因子结合蛋白4（IGFBP-4），以评估ERG表达对预后的影响（中位随访时间为4409天）。阳性HDAC 6染色与较低的无病生存率显著相关。此外，当HDAC 6的表达水平与IGFBP-4在细胞核中的表达相结合时，更准确地鉴定了预后不良的患者。这项研究已经确定了新的候选ERG的预后预测，我们认为，这些ERG的表达水平的综合评估将有助于ER阳性乳腺癌患者的临床有用的分层。
Estrogen receptor (ER)-positive breast cancer is a distinct subpopulation of breast cancer exhibiting a high response rate to endocrine therapy. However, not all ER-positive patients respond to the therapy, and a subgrouping of ER-positive patients based on the physiology of estrogen signaling is expected to be useful for predicting the prognosis. This study has revealed that selected estrogen-regulated genes (ERGs) are useful in identification of a poor-prognosis population among ER-positive breast cancer patients. First, the expression levels of 11 ERGs, selected based on our earlier microarray study in cultured cells, were analyzed by means of real-time reverse transcription-PCR in 14 ER-positive human breast cancer tissues. The patients were clearly divided into two groups in cluster analysis. Then, we examined the expression levels of two representative ERGs, histone deacetylase 6 (HDAC6) and insulin-like growth factor binding protein 4 (IGFBP-4), in 62 ER-positive patients with immunohistochemistry to assess the impact of ERG expression on prognosis (median follow-up 4409 days). Positive HDAC6 staining was significantly correlated with a lower disease-free survival rate. Moreover, when the expression level of HDAC6 was assessed in combination with IGFBP-4 expression in the nucleus, the poor-prognosis patients were more accurately identified. This study has identified new candidate ERGs for prediction of prognosis, and we suggest that combined assessment of the expression levels of these ERGs will contribute to the clinically useful stratification of ER-positive breast cancer patients.