miRNA 表达失调与 Oncotype DX DCIS 评分相关。

MiRNA expression deregulation correlates with the Oncotype DX DCIS score.

机构信息

Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, 07110, USA.

Department of Nephrology and Hypertension, Hadassah Medical Center, 91120, Jerusalem, Israel.

出版信息

Breast Cancer Res. 2022 Sep 12;24(1):62. doi: 10.1186/s13058-022-01558-4.

DOI:10.1186/s13058-022-01558-4

PMID:36096802

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9469592/

Abstract

BACKGROUND

Current clinical criteria do not discriminate well between women who will or those who will not develop ipsilateral invasive breast cancer (IBC), or a DCIS recurrence after a ductal carcinoma in situ (DCIS) diagnosis. The 12-gene Oncotype DX® DCIS assay (RT qPCR gene-based scoring system) was established and shown to predict the risk of subsequent ipsilateral IBC or DCIS recurrence. Recent studies have shown that microRNA (miRNA) expression deregulation can contribute to the development of IBC, but very few have evaluated miRNA deregulation in DCIS lesions. In this study, we sought to determine whether specific miRNA expression changes may correlate with Oncotype DX® DCIS scores.

METHODS

For this study, we used archived formalin-fixed, paraffin-embedded (FFPE) specimens from 41 women diagnosed with DCIS between 2012 and 2018. The DCIS lesions were stratified into low (n = 26), intermediate (n = 10), and high (n = 5) risk score groups using the Oncotype DX® DCIS assay. Total RNA was extracted from DCIS lesions by macro-dissection of unstained FFPE sections, and next-generation small-RNA sequencing was performed. We evaluated the correlation between miRNA expression data and Oncotype score, as well as patient age. RT-qPCR validations were performed to validate the topmost differentially expressed miRNAs identified between the different risk score groups.

RESULTS

MiRNA sequencing of 32 FFPE DCIS specimens from the three different risk group scores identified a correlation between expression deregulation of 17 miRNAs and Oncotype scores. Our analyses also revealed a correlation between the expression deregulation of 9 miRNAs and the patient's age. Based on these results, a total of 15 miRNAs were selected for RT-qPCR validation. Of these, miR-190b (p = 0.043), miR-135a (p = 0.05), miR-205 (p = 0.00056), miR-30c (p = 0.011), and miR-744 (p = 0.038) showed a decreased expression in the intermediate/high Oncotype group when compared to the low-risk score group. A composite risk score was established using these 5 miRNAs and indicated a significant association between miRNA expression deregulation and the Oncotype DX® DCIS Score (p < 0.0021), between high/intermediate and low risk groups.

CONCLUSIONS

Our analyses identified a subset of 5 miRNAs able to discriminate between Oncotype DX® DCIS score subgroups. Together, our data suggest that miRNA expression analysis may add value to the predictive and prognostic evaluation of DCIS lesions.

摘要

背景

目前的临床标准不能很好地区分哪些女性会发展为同侧浸润性乳腺癌（IBC），或哪些女性在导管原位癌（DCIS）诊断后会出现 DCIS 复发。12 基因 Oncotype DX® DCIS 检测（实时荧光定量 PCR 基因评分系统）已建立并证明可预测随后同侧 IBC 或 DCIS 复发的风险。最近的研究表明，微小 RNA（miRNA）表达失调可能导致 IBC 的发生，但很少有研究评估 DCIS 病变中的 miRNA 失调。在这项研究中，我们试图确定特定的 miRNA 表达变化是否与 Oncotype DX® DCIS 评分相关。

方法

本研究使用了 2012 年至 2018 年间诊断为 DCIS 的 41 名女性的存档福尔马林固定、石蜡包埋（FFPE）标本。使用 Oncotype DX® DCIS 检测将 DCIS 病变分为低（n=26）、中（n=10）和高（n=5）风险评分组。通过对未染色 FFPE 切片的宏观解剖，从 DCIS 病变中提取总 RNA，并进行下一代小 RNA 测序。我们评估了 miRNA 表达数据与 Oncotype 评分以及患者年龄之间的相关性。对不同风险评分组之间差异表达的最显著 miRNA 进行了 RT-qPCR 验证。

结果

对来自三个不同风险评分组的 32 个 FFPE DCIS 标本的 miRNA 测序，鉴定出 17 个 miRNA 的表达失调与 Oncotype 评分相关。我们的分析还揭示了 9 个 miRNA 的表达失调与患者年龄之间的相关性。基于这些结果，共选择了 15 个 miRNA 进行 RT-qPCR 验证。其中，miR-190b（p=0.043）、miR-135a（p=0.05）、miR-205（p=0.00056）、miR-30c（p=0.011）和 miR-744（p=0.038）在中间/高 Oncotype 组中的表达较低风险评分组降低。使用这 5 个 miRNA 建立了一个复合风险评分，并表明 miRNA 表达失调与 Oncotype DX® DCIS 评分之间存在显著关联（p<0.0021），在高/中风险组和低风险组之间存在显著关联。