Emmadi Rajyasree, Canestrari Emanuele, Arbieva Zarema H, Mu Wenbo, Dai Yang, Frasor Jonna, Wiley Elizabeth
Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
PLoS One. 2015 Dec 30;10(12):e0145346. doi: 10.1371/journal.pone.0145346. eCollection 2015.
Altered expression of miRNAs has been observed in many types of cancer, including breast cancer, and shown to contribute to cancer growth, aggressiveness, and response to therapies. In this pilot study, we investigated the possible correlation of miRNAs with risk of recurrence of estrogen receptor positive, lymph node-negative mammary carcinomas as determined by the Oncotype DX® Breast Cancer assay. To accomplish this, we extracted RNA from a collection of breast carcinomas that had previously been analyzed by Oncotype DX®. Multiple Let-7 family members were negatively correlated with the recurrence score (RS), which is consistent with their tumor suppressor properties. Additional miRNAs were found to positively correlate with RS, including miR-377-5p, miR-633b, miR-548t and miR-3648. Pathway analysis of putative and validated targets suggests that these miRNAs may have a diverse range of functions that may contribute to tumor recurrence. Taken together, these findings provide evidence that a miRNA expression signature can be developed to aid existing methods to determine the risk of recurrence for women with estrogen receptor positive breast cancers treated with endocrine therapy.
在包括乳腺癌在内的多种癌症中均观察到了微小RNA(miRNA)表达的改变,且已表明其与癌症生长、侵袭性及对治疗的反应有关。在这项初步研究中,我们通过Oncotype DX®乳腺癌检测法,研究了miRNA与雌激素受体阳性、淋巴结阴性乳腺癌复发风险之间的可能关联。为实现这一目的,我们从一组先前已通过Oncotype DX®分析的乳腺癌样本中提取了RNA。多个Let-7家族成员与复发评分(RS)呈负相关,这与其肿瘤抑制特性相符。还发现其他一些miRNA与RS呈正相关,包括miR-377-5p、miR-633b、miR-548t和miR-3648。对假定及已验证靶点的通路分析表明,这些miRNA可能具有多种功能,这些功能可能导致肿瘤复发。综上所述,这些发现为开发一种miRNA表达特征以辅助现有方法确定接受内分泌治疗的雌激素受体阳性乳腺癌女性的复发风险提供了证据。