Block Ines, Burton Mark, Sørensen Kristina P, Andersen Lars, Larsen Martin J, Bak Martin, Cold Søren, Thomassen Mads, Tan Qihua, Kruse Torben A
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Human Genetics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Oncotarget. 2018 Jan 9;9(10):9030-9042. doi: 10.18632/oncotarget.24088. eCollection 2018 Feb 6.
Current prognostic markers allocate the majority of lymph node (LN) negative and estrogen receptor (ER) positive breast cancer patients into the high-risk group. Accordingly, most patients receive systemic treatments although approximately 40% of these patients may have been cured by surgery and radiotherapy alone. Two studies identified seven prognostic microRNAs in systemically untreated, LN negative and ER positive breast cancer patients which may allow more precise patient classification. However, six of the seven microRNAs were analyzed in both studies but only found to be prognostic in one study. To validate their prognostic potential, we analyzed microRNA expression in an independent cohort ( = 110) using a pair-matched study design minimizing dependence of classical markers. The expression of hsa-miR-548c-5p was significantly associated with abridged disease-free survival (hazard ratio [HR]:1.96, = 0.027). Contradicting published results, high hsa-miR-516-3p expression was associated with favorable outcome (HR:0.29, = 0.0068). The association is probably time-dependent indicating later relapse. Additionally, re-analysis of previously published expression data of two matching cohorts ( = 100, = 255) supports an association of hsa-miR-128-3p with shortened disease-free survival (HR:2.48, = 0.0033) and an upregulation of miR-7-5p ( = 0.0038; = 0.039) and miR-210-3p ( = 0.031) in primary tumors of patients who experienced metastases. Further analysis may verify the prognostic potential of these microRNAs.
目前的预后标志物将大多数淋巴结(LN)阴性且雌激素受体(ER)阳性的乳腺癌患者归为高风险组。因此,大多数患者接受全身治疗,尽管这些患者中约40%可能仅通过手术和放疗就已治愈。两项研究在未经全身治疗、LN阴性且ER阳性的乳腺癌患者中鉴定出七种预后微小RNA,这可能使患者分类更精确。然而,这七种微小RNA中的六种在两项研究中均有分析,但仅在一项研究中发现具有预后意义。为验证其预后潜力,我们使用配对研究设计分析了一个独立队列(n = 110)中的微小RNA表达,以尽量减少经典标志物的依赖性。hsa-miR-548c-5p的表达与无病生存期缩短显著相关(风险比[HR]:1.96,P = 0.027)。与已发表结果相反,hsa-miR-516-3p高表达与良好预后相关(HR:0.29,P = 0.0068)。这种关联可能与时间有关,表明复发较晚。此外,对之前发表的两个匹配队列(n = 100,n = 255)的表达数据进行重新分析,支持hsa-miR-128-3p与无病生存期缩短相关(HR:2.48,P = 0.0033),以及在发生转移的患者原发肿瘤中miR-7-5p(P = 0.0038;q = 0.039)和miR-210-3p(P = 0.031)上调。进一步分析可能会验证这些微小RNA的预后潜力。