From the Department of Radiological Sciences, UCLA School of Medicine, Box 951721, CHS 17-135, Los Angeles, CA 90095-1721 (S.Y., L.D., N.J., D.H., M.D.K.); and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea (W.H., Y.K., J.H.K.).
Radiology. 2015 May;275(2):384-92. doi: 10.1148/radiol.15142698. Epub 2015 Feb 26.
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.
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.
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 × 10(6) reads per sample and identified 14 880 lncRNAs from a background of 189 883 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.
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.
对患有乳腺癌的女性进行放射基因组分析，研究定量计算机视觉提取的动态对比增强（DCE）磁共振（MR）成像表型、早期转移与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。
在这项经机构审查委员会批准的研究中，使用自动图像分析平台从 DCE MR 成像数据中提取 47 个计算定量特征，以筛选出与无转移生存（MFS）不良相关的 MR 成像生物标志物（n=19）。候选特征的 lncRNA 分子图谱是通过 RNA 测序特异性负二项式分布差异表达分析来定义的。然后，该放射基因组生物标志物前瞻性地应用于验证集（n=42），以便通过定量聚合酶链反应分析预测 MFS 和 lncRNA 表达。
定量 MR 成像特征，增强边缘分数，可预测训练集中的 MFS（P=0.007）。RNA 测序分析产生了每个样本平均 5570 万个读取，每个样本可识别 189883 个转录本背景下的 14880 个 lncRNA。放射基因组分析允许鉴定出三个以前未表征的和五个与高增强边缘分数显著相关的 lncRNA，包括同源盒转录物反义基因间 RNA（HOTAIR）（P＜0.05），这是乳腺癌患者 MFS 不良的已知预测因子。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 中四个的表达（P＜0.05）均相关，包括 HOTAIR。
增强边缘分数评分是一种定量 DCE MR 成像 lncRNA 放射基因组生物标志物，与早期转移和已知的转移进展预测因子 HOTAIR 的表达相关。
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