Subtype-specific micro-RNA expression signatures in breast cancer progression

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• 作者：Vilde D. Haakensen ; Vegard Nygaard ; Liliana Greger ; Miriam R. Aure ; Bastian Fromm ; Ida R.K. Bukholm ; Torben Lü ; ders ; Suet-Feung Chin ; Anna Git ; Carlos Caldas ; Vessela N. Kristensen ; Alvis Brazma ; Anne-Lise Bø ; rresen-Dale ; Eivind Hovig and Å ; slaug Helland
• 刊名：International Journal of Cancer
• 出版年：2016
• 出版时间：1 September 2016
• 年：2016
• 卷：139
• 期：5
• 页码：1117-1128
• 全文大小：704K
• ISSN：1097-0215

文摘

Robust markers of invasiveness may help reduce the overtreatment of in situ carcinomas. Breast cancer is a heterogeneous disease and biological mechanisms for carcinogenesis vary between subtypes. Stratification by subtype is therefore necessary to identify relevant and robust signatures of invasive disease. We have identified microRNA (miRNA) alterations during breast cancer progression in two separate datasets and used stratification and external validation to strengthen the findings. We analyzed two separate datasets (METABRIC and AHUS) consisting of a total of 186 normal breast tissue samples, 18 ductal carcinoma in situ (DCIS) and 1,338 invasive breast carcinomas. Validation in a separate dataset and stratification by molecular subtypes based on immunohistochemistry, PAM50 and integrated cluster classifications were performed. We propose subtype-specific miRNA signatures of invasive carcinoma and a validated signature of DCIS. miRNAs included in the invasive signatures include downregulation of miR-139-5p in aggressive subtypes and upregulation of miR-29c-5p expression in the luminal subtypes. No miRNAs were differentially expressed in the transition from DCIS to invasive carcinomas on the whole, indicating the need for subtype stratification. A total of 27 miRNAs were included in our proposed DCIS signature. Significant alterations of expression included upregulation of miR-21-5p and the miR-200 family and downregulation of let-7 family members in DCIS samples. The signatures proposed here can form the basis for studies exploring DCIS samples with increased invasive potential and serum biomarkers for in situ and invasive breast cancer.