Abnormal expression of miR-1 in breast carcinoma as a potent prognostic factor.
Abnormal expression of miR-1 in breast carcinoma as a potent prognostic factor.
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DOI：
10.1111/cas.12808
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发表时间：
2015-11
期刊：
影响因子：
5.7
通讯作者：
Suzuki T
中科院分区：
文献类型：
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作者：
Minemura H;Takagi K;Miki Y;Shibahara Y;Nakagawa S;Ebata A;Watanabe M;Ishida T;Sasano H;Suzuki T
转移性乳腺癌是一种高致死性疾病，评估与远处转移相关的生物标志物非常重要。MicroRNA（miRNA）是一种小的非蛋白质编码RNA，可调节多种细胞功能。最近的研究表明，一些miRNA在乳腺癌中的重要性，但绝大多数的miRNA的意义在很大程度上仍然不清楚在乳腺癌转移。因此，在本研究中，我们首先检测了miRNA在IV期乳腺癌组织中的表达谱，通过miRNA PCR阵列比较了I-III期病例，并确定miR-1是与远处转移最相关的miRNA。然而，miR-1尚未在乳腺癌组织中进行检测，其意义仍然未知。因此，我们使用原位杂交（ISH）进一步检测了乳腺癌中miR-1的表达。在20%的乳腺癌病例中，miR-1定位于癌细胞中，但在非肿瘤性乳腺或间质中可忽略不计。miR-1 ISH状态与乳腺癌的分期、病理T因子、淋巴结转移、远处转移、组织学分级、雌激素受体、孕激素受体和Ki-67显著相关。此外，使用多变量分析证明miR-1状态是无病生存期和乳腺癌特异性生存期的独立不良预后因素。这些发现表明，异常的miR-1表达与乳腺癌的侵袭性表型相关，并且miR-1状态是人类乳腺癌患者的有效预后因素。
Metastatic breast cancer remains a highly lethal disease, and it is very important to evaluate the biomarkers associated with the distant metastasis. MicroRNA (miRNA) are small non‐protein coding RNA that regulate various cellular functions. Recent investigations have demonstrated the importance of some miRNA in breast cancer, but the significance of the great majority of miRNA remains largely unclear in breast cancer metastasis. Therefore, in this study, we first examined expression profiles of miRNA in stage IV breast carcinoma tissues, comparing stage I–III cases by miRNA PCR array, and identified miR‐1 as the miRNA which was the most associated with the distant metastasis. However, miR‐1 has not yet been examined in breast carcinoma tissue, and its significance remains unknown. Therefore, we further examined miR‐1 expression in breast carcinoma using in situ hybridization (ISH). miR‐1 was localized in carcinoma cells in 20% of breast carcinoma cases, but it was negligible in non‐neoplastic mammary glands or stroma. miR‐1 ISH status was significantly associated with stage, pathological T factor, lymph node metastasis, distant metastasis, histological grade, estrogen receptor, progesterone receptor and Ki‐67 in breast carcinoma. Moreover, the miR‐1 status was demonstrated using multivariate analysis as an independent worse prognostic factor for both disease‐free and breast cancer‐specific survival. These findings suggest that abnormal miR‐1 expression is associated with an aggressive phenotype of breast carcinoma and that miR‐1 status is a potent prognostic factor in human breast cancer patients.