Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, California.
Moores Cancer Center, University of California, San Diego, La Jolla, California.
Cancer Epidemiol Biomarkers Prev. 2019 Sep;28(9):1525-1533. doi: 10.1158/1055-9965.EPI-18-1322. Epub 2019 Jun 11.
There is substantial variation in breast cancer survival rates, even among patients with similar clinical and genomic profiles. New biomarkers are needed to improve risk stratification and inform treatment options. Our aim was to identify novel miRNAs associated with breast cancer survival and quantify their prognostic value after adjusting for established clinical factors and genomic markers.
Using the Women's Healthy Eating and Living (WHEL) breast cancer cohort with >15 years of follow-up and archived tumor specimens, we assayed PAM50 mRNAs and 25 miRNAs using the Nanostring nCounter platform.
We obtained high-quality reads on 1,253 samples (75% of available specimens) and used an existing research-use algorithm to ascertain PAM50 subtypes and risk scores (ROR-PT). We identified miRNAs significantly associated with breast cancer outcomes and then tested these in independent TCGA samples. miRNAs that were also prognostic in TCGA samples were further evaluated in multiple regression Cox models. We also used penalized regression for unbiased discovery.
Two miRNAs, 210 and 29c, were associated with breast cancer outcomes in the WHEL and TCGA studies and further improved risk stratification within PAM50 risk groups: 10-year survival was 62% in the node-negative high miR-210-high ROR-PT group versus 75% in the low miR-210- high ROR-PT group. Similar results were obtained for miR-29c. We identified three additional miRNAs, 187-3p, 143-3p, and 205-5p, via penalized regression.
Our findings suggest that miRNAs might be prognostic for long-term breast cancer survival and might improve risk stratification. Further research to incorporate miRNAs into existing clinicogenomic signatures is needed.
即使患者具有相似的临床和基因组特征，乳腺癌的生存率也存在很大差异。需要新的生物标志物来改善风险分层并为治疗选择提供信息。我们的目的是鉴定与乳腺癌生存相关的新 miRNA，并在调整既定临床因素和基因组标记后量化其预后价值。
我们使用具有 >15 年随访和存档肿瘤标本的妇女健康饮食和生活（WHEL）乳腺癌队列，使用 Nanostring nCounter 平台检测 PAM50 mRNAs 和 25 个 miRNA。
我们获得了 1253 个样本（可用标本的 75%）的高质量读数，并使用现有的研究用算法确定了 PAM50 亚型和风险评分（ROR-PT）。我们鉴定了与乳腺癌结局显著相关的 miRNA，然后在独立的 TCGA 样本中进行了测试。在 TCGA 样本中具有预后意义的 miRNA 进一步在多元回归 Cox 模型中进行了评估。我们还使用了惩罚回归进行无偏发现。
两种 miRNA，210 和 29c，与 WHEL 和 TCGA 研究中的乳腺癌结局相关，并且在 PAM50 风险组内进一步改善了风险分层：淋巴结阴性高 miR-210-高 ROR-PT 组的 10 年生存率为 62%，而低 miR-210-高 ROR-PT 组为 75%。miR-29c 也得到了类似的结果。我们通过惩罚回归鉴定了另外三个 miRNA，187-3p、143-3p 和 205-5p。
我们的研究结果表明，miRNA 可能对乳腺癌的长期生存具有预后价值，并且可能改善风险分层。需要进一步研究将 miRNA 纳入现有的临床基因组特征。
