乳癌患者腫瘤組織中miR-21表現量與臨床病理特徵之關聯性

研究目的：近十幾年來，台灣女性乳癌的發生率逐年上升，且已躍升到女性癌症的首位。過去文獻指出，乳癌中 miR-21 之過度表現與乳癌的復發有關。本研究欲瞭解，於台灣女性乳癌中 miR-21 之表現情況及其與臨床因子的關聯性，並釐清 miR-21 與臨床因子的關聯性是否與抑制其標的基因 PTEN有關。研究方法及材料：本研究收集 120 位台灣女性乳癌患者之檢體，利用即時定量反轉錄聚合酶連鎖反應 （real-time RT-PCR） 方式分析 miR-21、 PTEN及乳癌篩選因子 （Estrogen receptor、Progesterone receptor 及 HER-2 receptor）之表現，並利用 Cell invasion and migration assay 及 Wound healing assay 分析三株乳癌細胞株 （T-47D、MDA-MB-231 及 MCF-7） 之浸潤及遷移能力。研究結果：在乳癌檢體中miR-21 與其目標基因 PTEN 並無統計上的關聯性（P=0.356），但與 HER-2/neu 之 mRNA表現呈正相關 （P=0.038）。於無病存活率（DFS）結果中發現，當 miR-21 高表現（p=0.047）、miR-21 及 HER-2/neu 皆為高表現（P=0.009）或miR-21 與 PTEN 皆高表現時（P=0.003），病人的無病存活率較差；PTEN 高表現時，病人的無病存活（P=0.024）也較差。顯示 miR-21、HER-2/neu 及 PTEN 之表現對於患者預後扮演重要角色，且皆與復發有關。於細胞實驗中亦可發現當 miR-21 表現高時，浸潤及遷移能力越強。結論：本研究中發現 miR-21、HER-2/neu 及 PTEN 之高表現與乳癌患者復發有關，但並不影響其下游PTEN的表現，因此可能有其他路徑參與miR-21所調控的乳癌致病過程，但仍需進一步研究。

Objective：Over the last decade, the incidence of breast cancer increased year by year, and the mortality rate is the top of female cancer in Taiwan. Previous study showed that overexpression of miR-21 was associated with recurrence in breast cancer. The aim of this study was to analyze the association of miR-21 expression and clinic pathologic data and to investigate whether the affect of miR-21 through PTEN pathway. Materials and Methods：A total of 120 female breast cancer patients, who were enrolled at a single medical center in Taichung. MiR-21, PTEN, hormone receptor (Estrogen receptor、Progesterone receptor) and HER-2 (Human Epidermal Growth Factor Receptor 2) receptor were analyzed by quantitative RT-PCR. The function of invasion and migration of three breast cancer cell lines (T-47D, MDA-MB-231 and MCF-7) were analyzed by invasion、migration and wound healing assay.Results：Our data showed that no any significantly difference was found between miR-21 and PTEN. MiR-21 expression was positive correlated with HER-2/neu mRNA levels (P=0.038). Patients with high miR-21 had poor disease-free survival (p=0.047) compared with low miR-21 expression patients. In addition, patients with high PTEN expression had poor disease-free survival (P=0.024). We also found that patients with miR-21 high/ HER-2/neu high or miR-21 high/ PTEN high had poor disease-free survival (miR-21/HER-2/neu, p=0.009; miR-21/PTEN, p=0.003). Thus, we suggested that the expressions of miR-21, HER-2/neu and PTEN play important roles in prognosis and associated with recurrence in breast cancer. These results were also confirmed in cell model experiments.Conclusion：In this study, we found that the expression of miR-21, HER-2/neu, and PTEN were associated with the recurrence of breast cancer. Thus, we suggested that the other pathways maybe involved in miR-21 mediated pathogenesis of breast cancer.