肝细胞癌微血管侵犯的影响因素分析及基于三维可视化列线图模型构建

Influencing factors for microvascular invasion in hepatocellular carcinoma and construction of nomogram model based on three‑dimensional visualization

  • 摘要:
    目的 探讨肝细胞癌微血管侵犯(MVI)的影响因素及基于三维可视化的列线图模型构建。
    方法 采用回顾性队列研究方法。收集2018年5月至2021年5月河南大学人民医院收治的190例肝细胞癌患者的临床病理资料;男148例,女42例,年龄为(58±12)岁。190例患者通过随机数字表法按7∶3比例随机分为训练集133例和验证集57例。采用腹腔三维可视化系统进行肿瘤形态等影像学特征分析。观察指标:(1)肝细胞癌MVI的影响因素分析。(2)肝细胞癌MVI的列线图模型构建及评估。正态分布的计量资料以x±s表示,组间比较采用独立样本t检验。偏态分布的计量资料以MQ1,Q3)表示,组间比较采用非参数秩和检验。计数资料以绝对数表示,组间比较采用χ²检验。单因素分析采用对应的统计学方法。多因素分析采用二元Logistic回归模型。绘制受试者工作特征(ROC)曲线,以曲线下面积(AUC)、校准曲线、决策曲线评估列线图模型。
    结果 (1)肝细胞癌MVI的影响因素分析。190例肝细胞癌患者中,MVI阳性97例(训练集63例、验证集34例),MVI阴性93例(训练集70例、验证集23例)。多因素分析结果显示:甲胎蛋白、血管内皮生长因子、肿瘤体积、肿瘤数量、肿瘤形态是影响训练集肝细胞癌患者MVI的独立因素(比值比=5.06,3.62,1.00,2.02,2.59,95%可信区间为1.61~15.90,1.28~10.20,1.00~1.01,1.02~3.98,1.03~6.52,P<0.05)。(2)肝细胞癌MVI的列线图模型构建及评估。纳入多因素分析结果构建肝细胞癌MVI的列线图预测模型。ROC曲线显示:列线图模型训练集的AUC为0.85(95%可信区间为0.79~0.92),根据约登指数计算列线图模型的最佳分数截断值为0.51、灵敏度为0.71、特异度为0.84,验证集上述指标分别为0.92(95%可信区间为0.85~0.99)、0.50、0.90、0.82。训练集的列线图评分总分越高提示肝细胞癌发生MVI的风险越大。列线图模型训练集和验证集的校准曲线与标准曲线均贴合较好,校准度较高。决策曲线显示:列线图模型净收益较高。
    结论 甲胎蛋白、血管内皮生长因子、肿瘤体积、肿瘤数量、肿瘤形态是影响肝细胞癌患者MVI的独立因素。基于三维可视化影像学特征构建的列线图评分模型可预测肝细胞癌MVI。

     

    Abstract:
    Objective To investigate the influencing factors for microvascular invasion (MVI) in hepatocellular carcinoma based on three‑dimensional visualization and the construction of its nomogram model.
    Methods The retrospective cohort study method was conducted. The clinico-pathological data of 190 patients with hepatocellular carcinoma who were admitted to Henan University People′s Hospital from May 2018 to May 2021 were collected. There were 148 males and 42 females, aged (58±12)years. The 190 patients were randomly divided into the training set of 133 cases and the validation set of 57 cases by the method of random number table in the ratio of 7:3. The abdominal three‑dimensional visualization system was used to characterize the tumor morphology and other imaging features. Observation indicators: (1) analysis of influencing factors for MVI in hepatocellular carcinoma; (2) construction and evaluation of nomogram model of MVI in hepatocellular carcinoma. Measurement data with normal distribution were expressed as Mean±SD, and independent sample t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(Q1, Q3), and non‑parametric rank sum test was used for comparison between groups. Count data were expressed as absolute numbers, and the chi‑square test was used for comparison between groups. Corresponding statistical methods were used for univariate analysis. Binary Logistic regression model was used for multivariate analysis. Receiver operator characteristic (ROC) curves were plotted, and the nomogram model was assessed by area under the curve (AUC), calibration curve, and decision curve.
    Results (1) Analysis of influencing factors for MVI in hepatocellular carcinoma. Among 190 patients with hepatocellular carcinoma, there were 97 cases of positive MVI (including 63 cases in the training set and 34 cases in the validation set) and 93 cases of negative MVI (including 70 cases in the training set and 23 cases in the validation set). Results of multivariate analysis showed that alpha‑fetoprotein, vascular endothelial growth factor, tumor volume, the number of tumors, and tumor morphology were independent factors affecting the MVI of patients with hepatocellular carcinoma (odds ratio=5.06, 3.62, 1.00, 2.02, 2.59, 95% confidence interval as 1.61-15.90, 1.28-10.20, 1.00-1.01, 1.02-3.98, 1.03-6.52, P<0.05). (2) Construction and evaluation of nomogram model of MVI in hepatocellular carcinoma. The results of multivariate analysis were incorporated to construct a nomogram prediction model for MVI of hepatocellular carcinoma. ROC curves showed that the AUC of the training set of nomogram model was 0.85 (95% confidence interval as 0.79-0.92), the optimal fractional cutoff based on the Jordon′s index was 0.51, the sensitivity was 0.71, and the specificity was 0.84. The above indicators of validation set were 0.92 (95% confidence interval as 0.85-0.99), 0.50, 0.90, and 0.82, respectively. The higher total score of the training set suggested a higher risk of MVI in hepatocellular carcinoma. The calibration curves of both training and validation sets of nomogram model fitted well with the standard curves and have a high degree of calibration. The decision curve showed a high net gain of nomogram model.
    Conclusions Alpha‑fetoprotein, vascular endothelial growth factor, tumor volume, the number of tumors, and tumor morphology are independent influencing factors for MVI in patients with hepatocellular carcinoma. A nomogram model constructed based on three‑dimensional visualized imaging features can predict MVI in hepatocellular carcinoma.

     

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