【摘要】 目的通过肝细胞癌影像特征和基因模块关联的基因影像学方法,获取生物可解释的影像学标记物。方法从癌症基因组数据库获取371例肝细胞癌基因表达数据,其中37例有对应的术前增强CT数据。从勾画的肿瘤区域提取639维定量影像特征,基于一致性指数标准,筛选出12个影像特征。对肝细胞癌基因表达数据进行聚类,得到聚类基因模块,并与影像特征构建Spearman相关图,筛选出与基因模块关联的影像特征,最后用Cox回归模型评估其是否具有预后功能。结果 12个影像特征中,4个与预后的基因模块显著相关,3个与生存预后显著相关。其中,小波分量高灰度级小区域增强特征,与代表糖链生物合成的基因模块显著相关,且该影像特征与病人的总体生存周期(P=0.006,风险比=0.16)显著相关;低灰度级长游程增强纹理特征,与代表血管生成的基因模块显著相关,且与总体生存周期(P=0.049,风险比=3.21)显著相关。结论描述肿瘤小波频率和纹理的影像特征有可解释的生物学含义,并且与生存周期显著相关,这些特征可作为肝细胞癌潜在的影像学标记物。更多还原

【Abstract】 Objective To identify imaging biomarkers with biological interpretation in hepatocellular carcinoma(HCC) using radiogenomic methodology that associates computed tomography(CT) imaging features with gene modules. Methods Three hundred and seventy one patients who had gene expression profiles from the Cancer Genome Atlas were retrospectively analyzed. For the 37 patients with contrast-enhanced CT imaging data,639 quantitative imaging features were extracted from delineated tumor. Twelve imaging features were selected based on concordance index(CI) criteria. Gene modules acquired from a clustering method were associated with imaging features using Spearman rank correlation; the imaging features that significantly correlated with gene modules were obtained. These imaging features were evaluated with Cox’s proportional hazard models to determine their prognostic capabilities. Results Four of 12 imaging features significantly correlated with the prognostic gene modules,and 3 were associated with survival significance. Among these,the wavelet feature Small Zone High Gray-Level Emphasis of wavelet component,which was significantly correlated with the prognostic gene module representing N-Glycan biosynthesis,was predictive of overall survival(OS)(P =0. 006,hazard ratio = 0. 16). The texture feature Long Run Low Gray-Level Emphasis,which was correlated with the prognostic gene module representing angiogenesis,also predicted OS(P = 0. 049,hazard ratio =3. 21). Conclusion Imaging features depicting the wavelet frequency and texture have interpretable biological meaning and can predict overall survival,thereby could be potential imaging biomarkers for HCC patients.更多还原