Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Department of Radiation Oncology, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Cancer Hospital and Institute, Huaiyin Region, Jinan, Shandong, China.
Cancer Med. 2020 Jul;9(14):5065-5074. doi: 10.1002/cam4.3115. Epub 2020 May 27.
We aimed to establish radiotranscriptomics signatures based on serum miRNA levels and computed tomography (CT) texture features and develop nomogram models for predicting radiotherapy response in patients with nonsmall cell lung cancer (NSCLC).
We first used established radioresistant NSCLC cell lines for miRNA selection. At the same time, patients (103 for training set and 71 for validation set) with NSCLC were enrolled. Their pretreatment contrast-enhanced CT texture features were extracted and their serum miRNA levels were obtained. Then, radiotranscriptomics feature selection was implemented with the least absolute shrinkage and selection operator (LASSO), and signatures were generated by logistic or Cox regression for objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). Afterward, radiotranscriptomics signature-based nomograms were constructed and assessed for clinical use.
Four miRNAs and 22 reproducible contrast-enhanced CT features were used for radiotranscriptomics feature selection and we generated ORR-, OS-, and PFS- related radiotranscriptomics signatures. In patients with NSCLC who received radiotherapy, the radiotranscriptomics signatures were independently associated with ORR, OS, and PFS in both the training (OR: 2.94, P < .001; HR: 2.90, P < .001; HR: 3.58, P = .001) and validation set (OR: 2.94, P = .026; HR: 2.14, P = .004; HR: 2.64, P = .016). We also obtained a satisfactory nomogram for ORR. The C-index values for the ORR nomogram were 0.86 [95% confidence interval (CI), 0.75 to 0.92] in the training set and 0.81 (95% CI, 0.69 to 0.89) in the validation set. The calibration-in-the-large and calibration slope performed well. Decision curve analysis indicated a satisfactory net benefit.
The radiotranscriptomics signature could be an independent biomarker for evaluating radiotherapeutic responses in patients with NSCLC. The radiotranscriptomics signature-based nomogram could be used to predict patients' ORR, which would represent progress in individualized medicine.
我们旨在基于血清 miRNA 水平和计算机断层扫描(CT)纹理特征建立放射转录组学特征,并为非小细胞肺癌(NSCLC)患者的放射治疗反应建立预测列线图模型。
我们首先使用已建立的放射抵抗 NSCLC 细胞系进行 miRNA 选择。同时,纳入 103 例(训练集)和 71 例(验证集)NSCLC 患者。提取其治疗前增强 CT 纹理特征,并获得其血清 miRNA 水平。然后,使用最小绝对值收缩和选择算子(LASSO)进行放射转录组学特征选择,并通过逻辑或 Cox 回归生成客观反应率(ORR)、总生存期(OS)和无进展生存期(PFS)相关的放射转录组学特征。之后,构建放射转录组学特征的列线图并评估其临床应用。
选择了 4 个 miRNA 和 22 个可重复的增强 CT 特征用于放射转录组学特征选择,并生成了与 ORR、OS 和 PFS 相关的放射转录组学特征。在接受放射治疗的 NSCLC 患者中,放射转录组学特征在训练集(OR:2.94,P<0.001;HR:2.90,P<0.001;HR:3.58,P=0.001)和验证集(OR:2.94,P=0.026;HR:2.14,P=0.004;HR:2.64,P=0.016)中均与 ORR、OS 和 PFS 独立相关。我们还获得了一个用于 ORR 的满意列线图。ORR 列线图的 C 指数值在训练集和验证集分别为 0.86[95%置信区间(CI):0.75 至 0.92]和 0.81(95%CI:0.69 至 0.89)。大校准和校准斜率表现良好。决策曲线分析表明有较好的净获益。
放射转录组学特征可能是评估 NSCLC 患者放射治疗反应的独立生物标志物。基于放射转录组学特征的列线图可用于预测患者的 ORR,这将代表个体化医学的进步。