Breast Cancer: Radiogenomic Biomarker Reveals Associations among Dynamic Contrast-enhanced MR Imaging, Long Noncoding RNA, and Metastasis
Breast Cancer: Radiogenomic Biomarker Reveals Associations among Dynamic Contrast-enhanced MR Imaging, Long Noncoding RNA, and Metastasis
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DOI：
10.1148/radiol.15142698
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发表时间：
2015-05-01
期刊：
影响因子：
19.7
通讯作者：
Kuo, Michael D.
中科院分区：
文献类型：
--
作者：
Yamamoto, Shota;Han, Wonshik;Kuo, Michael D.
目的：对乳腺癌患者进行放射基因组学分析，研究计算机视觉提取的动态对比材料增强（DCE）磁共振（MR）成像表型、早期转移和通过高分辨率下一代RNA测序确定的长链非编码RNA（lncRNA）表达之间的多尺度关系。材料和方法：在这个机构审查委员会批准的研究中，自动图像分析平台从训练组（n = 19）中的DCE MR成像数据中提取47个计算定量特征，以筛选指示不良无转移存活（MFS）的MR成像生物标志物。通过使用RNA测序特异性负二项分布差异表达分析来定义候选特征的lncRNA分子景观。然后，这种放射性基因组生物标志物被前瞻性地应用到一个验证集（n = 42），允许预测MFS和lncRNA的表达，通过使用定量聚合酶链反应analysis.Results：定量MR成像功能，增强边缘分数，预测MFS在训练集（P = 0.007）。RNA测序分析得到每个样品平均55.7 × 10（6）个读数，并从每个样品189883个转录本的背景中鉴定出14880个lncRNA。放射基因组学分析允许鉴定与高增强边缘分数显著相关的三种先前未表征的和五种命名的lncRNA，包括同源框转录物反义基因间RNA（HOTAIR）（P <0.05），这是乳腺癌患者中不良MFS的已知预测因子。独立验证证实了增强边缘分数表型与MFS（P = 0.002）和前五个差异表达lncRNA中的四个（P <0.05）的表达（包括HOTAIR.Conclusion：增强边缘分数评分，一种定量DCE MR成像lncRNA放射基因组学生物标志物，与早期转移和转移进展的已知预测因子HOTAIR的表达相关。(C)RSNA，2015年
Purpose: To perform a radiogenomic analysis of women with breast cancer to study the multiscale relationships among quantitative computer vision-extracted dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging phenotypes, early metastasis, and long noncoding RNA (lncRNA) expression determined by means of high-resolution next-generation RNA sequencing.Materials and Methods: In this institutional review board-approved study, an automated image analysis platform extracted 47 computational quantitative features from DCE MR imaging data in a training set (n = 19) to screen for MR imaging biomarkers indicative of poor metastasis-free survival (MFS). The lncRNA molecular landscape of the candidate feature was defined by using an RNA sequencing-specific negative binomial distribution differential expression analysis. Then, this radiogenomic biomarker was applied prospectively to a validation set (n = 42) to allow prediction of MFS and lncRNA expression by using quantitative polymerase chain reaction analysis.Results: The quantitative MR imaging feature, enhancing rim fraction score, was predictive of MFS in the training set (P = .007). RNA sequencing analysis yielded an average of 55.7 x 10(6) reads per sample and identified 14880 lncRNAs from a background of 189883 transcripts per sample. Radiogenomic analysis allowed identification of three previously uncharacterized and five named lncRNAs significantly associated with high enhancing rim fraction, including Homeobox transcript antisense intergenic RNA (HOTAIR) (P < .05), a known predictor of poor MFS in patients with breast cancer. Independent validation confirmed the association of the enhancing rim fraction phenotype with both MFS (P = .002) and expression of four of the top five differentially expressed lncRNAs (P < .05), including HOTAIR.Conclusion: The enhancing rim fraction score, a quantitative DCE MR imaging lncRNA radiogenomic biomarker, is associated with early metastasis and expression of the known predictor of metastatic progression, HOTAIR. (C) RSNA, 2015