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CT纹理分析:评估结直肠癌KRAS突变状态的潜在生物标志物

CT Texture Analysis: A Potential Biomarker for Evaluating KRAS Mutational Status in Colorectal Cancer.

作者信息

Cao Jian, Wang Guo Rong, Wang Zhi Wei, Jin Zheng Yu

机构信息

Department of Radiology, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

出版信息

Chin Med Sci J. 2020 Dec 31;35(4):306-314. doi: 10.24920/003770.

Abstract

Objective Texture analysis is deemed to reflect intratumor heterogeneity invisible to the naked eyes. The aim of this study was to evaluate the feasibility of assessing the KRAS mutational status in colorectal cancer (CRC) patients using CT texture analysis. Methods This retrospective study included 92 patients who had histopathologically confirmed CRC and underwent preoperative contrast-enhanced CT examinations. The patients were assigned into a training cohort (=51) and a validation cohort (=41). We placed the region of interest in the tumour regions on the selected axial images using software of TexRad to extract a series of quantitative parameters based on the spatial scaling factors (SSFs), including mean, standard deviation (SD), entropy, mean of positive pixels (MPP), skewness, and kurtosis. The texture parameters and clinical characteristics (age, gender, tumour location, histopathology, tumour size, T, N, M stages) were compared between the mutated and wild-type KRAS patient groups in training cohort and validation cohort. Before building the multiple feature classifier, we calculated the correlations of the features using Pearson's correlation coefficient, and if any two features were significantly correlated, the one with lower AUC was removed. Ultimately, only the most discriminative isolated features were combined to train a supporting vector machine (SVM) classifier. The receiver operating characteristic (ROC) curve was processed for evaluating the diagnostic efficiency of texture parameters in differentiating CRC patients with mutated KRAS from those with wild-type KRAS. Results None of the clinical characteristics were significant different between CRC patients with wild-type KRAS and mutated KRAS in both cohorts. For predicting the expression of mutated KRAS in CRC patients, the perfect model which combined skewness on SSF 5 by unenhanced CT, entropy on SSF 2, skewness and kurtosis on SSF 0, and kurtosis and mean on SSF 3 by enhanced CT, showed a desirable AUC of 0.951 (95% : 0.895-1, <0.001), with a sensitivity of 88.9% and a specificity of 91.7%, when the cut-off value was 0.46 in the training cohort; while in the validation cohort, the AUC value was 0.995 (95% : 0.982-1, <0.001), the sensitivity was 100%, and the specificity was 93.7% when the cut-off value was 0.28. Conclusion It is feasible to evaluate the KRAS mutational status in CRC using CT texture analysis.

摘要

目的 纹理分析被认为可反映肉眼不可见的肿瘤内异质性。本研究旨在评估使用CT纹理分析评估结直肠癌(CRC)患者KRAS突变状态的可行性。方法 这项回顾性研究纳入了92例经组织病理学确诊为CRC并接受术前对比增强CT检查的患者。将患者分为训练队列(n = 51)和验证队列(n = 41)。我们使用TexRad软件在选定的轴位图像上的肿瘤区域放置感兴趣区,以基于空间缩放因子(SSF)提取一系列定量参数,包括均值、标准差(SD)、熵、阳性像素均值(MPP)、偏度和峰度。在训练队列和验证队列中,比较突变型和野生型KRAS患者组之间的纹理参数和临床特征(年龄、性别、肿瘤位置、组织病理学、肿瘤大小、T、N、M分期)。在构建多特征分类器之前,我们使用Pearson相关系数计算特征之间的相关性,如果任意两个特征显著相关,则去除AUC较低的那个。最终,仅将最具判别力的孤立特征组合起来训练支持向量机(SVM)分类器。处理受试者工作特征(ROC)曲线以评估纹理参数在区分KRAS突变型CRC患者和野生型CRC患者中的诊断效率。结果 在两个队列中,野生型KRAS和突变型KRAS的CRC患者之间的临床特征均无显著差异。对于预测CRC患者中突变型KRAS的表达,结合平扫CT在SSF 5上的偏度、SSF 2上的熵、SSF 0上的偏度和峰度以及增强CT在SSF 3上的峰度和均值的完美模型,在训练队列中,当截断值为0.46时,显示出理想的AUC为0.951(95%CI:0.895 - 1,P < 0.001),灵敏度为88.9%,特异性为91.7%;而在验证队列中,AUC值为0.995(95%CI:0.982 - 1,P < 0.001),灵敏度为100%,当截断值为0.28时,特异性为93.7%。结论 使用CT纹理分析评估CRC患者的KRAS突变状态是可行的。

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