Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status

被引:92
作者
Rask, Lene [1 ,2 ]
Balslev, Eva [3 ]
Sokilde, Rolf [5 ]
Hogdall, Estrid [3 ]
Flyger, Henrik [4 ]
Eriksen, Jens [1 ]
Litman, Thomas [5 ]
机构
[1] Univ Copenhagen, Herlev Hosp, Dept Oncol 54O5, DK-2730 Herlev, Denmark
[2] Univ Copenhagen, Fac Hlth Sci, DK-2200 Copenhagen N, Denmark
[3] Univ Copenhagen, Herlev Hosp, Dept Pathol, DK-2730 Herlev, Denmark
[4] Univ Copenhagen, Herlev Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark
[5] Exiqon AS, DK-2950 Vedbaek, Denmark
关键词
Breast cancer; miRNA; miR-21; miR-486; miR-139; Biomarker; TUMOR-SUPPRESSOR GENE; MICRORNA EXPRESSION; DUCTAL ADENOCARCINOMAS; COLORECTAL-CANCER; GASTRIC-CANCER; RT-PCR; METASTASIS; CARCINOMA; PTEN; MICROARRAY;
D O I
10.1007/s13402-014-0176-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Therapeutic decisions in breast cancer are increasingly guided by prognostic and predictive biomarkers. Non-protein-coding microRNAs (miRNAs) have recently been found to be deregulated in breast cancers and, in addition, to be correlated with several clinico-pathological features. One of the most consistently up-regulated miRNAs is miR-21. Here, we specifically searched for differentially expressed miRNAs in high-risk breast cancer patients as compared to low-risk breast cancer patients. In the same patients, we also compared miR-21 expression with the expression of its presumed target PTEN. Both microarray and RT-qPCR techniques were used to assess miRNA expression levels in lymph node-positive and -negative human invasive ductal carcinoma tissues. Simultaneously, PTEN protein expression levels were assessed using immunohistochemistry. miR-486-5p and miR-139-5p were found to be down-regulated in patients with lymph node metastases, whereas miR-21 was found to be up-regulated in patients with a positive lymph node status. miR-21 expression levels were found to significantly correlate with tumour size (r = 0.403, p = 0.009; Spearman's rank), whereas no relation was found between miR-21 and PTEN expression levels (Kruskal-Wallis test). Down-regulation of miR-486-5p and miR-139-5p, in conjunction with up-regulation of miR-21, may represent a useful signature for the identification of high-risk breast cancer patients.
引用
收藏
页码:215 / 227
页数:13
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