miR-29b 在良恶性乳腺肿瘤中的表达分析：浸润性导管癌有希望的预后生物标志物，其表达状态可能与组织类型有关。

Expression Analysis of miR-29b in Malignant and Benign Breast Tumors: A Promising Prognostic Biomarker for Invasive Ductal Carcinoma With a Possible Histotype-Related Expression Status.

机构信息

First Department of Pathology, School of Health Sciences, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece; Department of Pathology, "Saint Savvas" Cancer Hospital of Athens, Athens, Greece.

Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.

出版信息

Clin Breast Cancer. 2018 Aug;18(4):305-312.e3. doi: 10.1016/j.clbc.2017.11.007. Epub 2017 Nov 21.

DOI:10.1016/j.clbc.2017.11.007

PMID:29422258

Abstract

BACKGROUND

Aberrations in microRNA levels seem to provide valuable information regarding breast cancer prognosis and therapy. In this study, we sought to analyze miR-29b expression in breast tumors and thus explore its clinical value.

MATERIALS AND METHODS

One hundred twenty-one malignant and 56 benign breast tissue specimens were collected and subjected to extraction of total RNA, which was polyadenylated and reverse transcribed to cDNA. Subsequently, a highly sensitive quantitative real-time polymerase chain reaction protocol was developed and miR-29b levels, estimated via the comparative C method, were finally subjected to comprehensive statistical analysis.

RESULTS

MiR-29b levels did not differ between the analyzed benign and malignant breast tissue specimens, but were found to be significantly (P = .010) decreased in invasive ductal adenocarcinomas compared with their lobular counterparts, albeit receiver operating characteristics curve analysis did not verify the latter correlation. Additionally, miR-29b expression was elevated in samples with positive estrogen receptor status (P = .021) in the overall population, whereas it was negatively correlated (P = .035) with primary tumor staging in the ductal subset and increased in poorly-differentiated tumors of lobular origin (P = .041). Furthermore, Kaplan-Meier and Cox regression analyses showed that patients with ductal carcinoma and elevated miR-29b levels had a significantly longer disease-free survival (P = .010) and a lower risk to relapse (hazard ratio = 0.35, 95% confidence interval, 0.15-0.81; P = .014).

CONCLUSION

Our results provide evidence that miR-29b levels constitute a promising biomarker of favorable prognosis for patients with invasive ductal breast carcinoma and imply that its expression status might be affected by the histological origin of breast malignancy.

摘要

背景

miRNA 水平的异常似乎为乳腺癌的预后和治疗提供了有价值的信息。在本研究中，我们试图分析乳腺癌肿瘤中的 miR-29b 表达，从而探索其临床价值。

材料与方法

收集了 121 例恶性和 56 例良性乳腺组织标本，提取总 RNA，经 poly(A)加尾和反转录为 cDNA。随后，建立了一种高灵敏度的实时定量聚合酶链反应方案，通过比较 C 法估计 miR-29b 水平，最后进行综合统计分析。

结果

分析的良性和恶性乳腺组织标本之间 miR-29b 水平没有差异，但在浸润性导管腺癌与小叶癌相比，其水平显著降低（P=0.010），尽管接受者操作特征曲线分析未验证后者的相关性。此外，在总人群中，miR-29b 表达在雌激素受体阳性的样本中升高（P=0.021），而在导管亚组中与原发性肿瘤分期呈负相关（P=0.035），在小叶来源的低分化肿瘤中升高（P=0.041）。此外，Kaplan-Meier 和 Cox 回归分析显示，miR-29b 水平升高的导管癌患者无病生存时间显著延长（P=0.010），复发风险降低（风险比=0.35，95%置信区间，0.15-0.81；P=0.014）。