Li Hui, Zhu Yitan, Burnside Elizabeth S, Huang Erich, Drukker Karen, Hoadley Katherine A, Fan Cheng, Conzen Suzanne D, Zuley Margarita, Net Jose M, Sutton Elizabeth, Whitman Gary J, Morris Elizabeth, Perou Charles M, Ji Yuan, Giger Maryellen L
Department of Radiology, The University of Chicago, Chicago, IL, USA.
Program of Computational Genomics & Medicine, NorthShore University HealthSystem, Evanston, IL, USA.
NPJ Breast Cancer. 2016;2:16012-. doi: 10.1038/npjbcancer.2016.12. Epub 2016 May 11.
Using quantitative radiomics, we demonstrate that computer-extracted magnetic resonance (MR) image-based tumor phenotypes can be predictive of the molecular classification of invasive breast cancers. Radiomics analysis was performed on 91 MRIs of biopsy-proven invasive breast cancers from National Cancer Institute's multi-institutional TCGA/TCIA. Immunohistochemistry molecular classification was performed including estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and for 84 cases, the molecular subtype (normal-like, luminal A, luminal B, HER2-enriched, and basal-like). Computerized quantitative image analysis included: three-dimensional lesion segmentation, phenotype extraction, and leave-one-case-out cross validation involving stepwise feature selection and linear discriminant analysis. The performance of the classifier model for molecular subtyping was evaluated using receiver operating characteristic analysis. The computer-extracted tumor phenotypes were able to distinguish between molecular prognostic indicators; area under the ROC curve values of 0.89, 0.69, 0.65, and 0.67 in the tasks of distinguishing between ER+ versus ER-, PR+ versus PR-, HER2+ versus HER2-, and triple-negative versus others, respectively. Statistically significant associations between tumor phenotypes and receptor status were observed. More aggressive cancers are likely to be larger in size with more heterogeneity in their contrast enhancement. Even after controlling for tumor size, a statistically significant trend was observed within each size group ( = 0.04 for lesions ≤ 2 cm; = 0.02 for lesions >2 to ≤5 cm) as with the entire data set (-value = 0.006) for the relationship between enhancement texture (entropy) and molecular subtypes (normal-like, luminal A, luminal B, HER2-enriched, basal-like). In conclusion, computer-extracted image phenotypes show promise for high-throughput discrimination of breast cancer subtypes and may yield a quantitative predictive signature for advancing precision medicine.
通过定量放射组学,我们证明基于计算机提取的磁共振(MR)图像的肿瘤表型可预测浸润性乳腺癌的分子分类。对来自美国国立癌症研究所多机构TCGA/TCIA的91例经活检证实的浸润性乳腺癌的MRI进行了放射组学分析。进行了免疫组织化学分子分类,包括雌激素受体、孕激素受体、人表皮生长因子受体2,并且对84例进行了分子亚型分类(正常样、腔面A型、腔面B型、HER2富集型和基底样型)。计算机化定量图像分析包括:三维病变分割、表型提取以及留一法交叉验证,其中涉及逐步特征选择和线性判别分析。使用受试者工作特征分析评估分子亚型分类器模型的性能。计算机提取的肿瘤表型能够区分分子预后指标;在区分ER+与ER-、PR+与PR-、HER2+与HER2-以及三阴性与其他类型的任务中,ROC曲线下面积值分别为0.89、0.69、0.65和0.67。观察到肿瘤表型与受体状态之间存在统计学上的显著关联。侵袭性更强的癌症可能体积更大,其对比增强的异质性更高。即使在控制肿瘤大小后,在每个大小组中也观察到了统计学上的显著趋势(对于≤2 cm的病变,P = 0.04;对于>2至≤5 cm的病变,P = 0.02),这与整个数据集(P值 = 0.006)中增强纹理(熵)与分子亚型(正常样、腔面A型、腔面B型、HER2富集型、基底样型)之间的关系相同。总之,计算机提取的图像表型在高通量区分乳腺癌亚型方面显示出前景,并且可能产生用于推进精准医学的定量预测特征。