基于术前HSP90α、LMR构建预测肝内胆管癌术后教科书式结局的列线图模型及模型评估

Establishment and validation of nomogram model based on perioperative HSP90αand LMR in predicting textbook outcome of intrahepatic cholangiocarcinoma

目的基于术前热休克蛋白90α(HSP90α)、淋巴细胞/单核细胞比值(LMR)构建预测肝内胆管癌术后教科书式结局(TO)列线图模型,并评估模型预测价值。方法回顾性分析2022年1月至2023年12月承德市中心医院收治的210例肝内胆管癌患者资料,其中男性122例,女性88例,年龄(61.3±5.5)岁。采用随机数字表法以7:3的比例将210例患者分为训练集(n=147)和测试集(n=63)。训练集患者依据是否达到TO分为TO组(n=39)和非TO组(n=108)。比较两组肿瘤长径<5 cm、淋巴结转移、大血管侵犯、术前HSP90α降低、术前LMR升高等情况,基于训练集采用单因素和多因素logistic回归分析肝内胆管癌患者术后实现TO的影响因素,基于多因素结果使用R4.3.0软件构建实现TO的预测模型。通过受试者工作特征(ROC)曲线、校准曲线、决策曲线分析评估模型(Bootstrap法抽样)。结果多因素logistic回归分析,肿瘤长径<5 cm(OR=1.917,95%CI:1.104~4.024)、无淋巴结转移(OR=2.489,95%CI:1.030~3.619)、无大血管侵犯(OR=2.565,95%CI:2.097~5.093)、术前HSP90α降低(OR=3.161,95%CI:2.536~5.358)、术前LMR升高(OR=2.088,95%CI:1.454~4.262)是肝内胆管癌患者术后实现TO的影响因素(均P<0.05)。基于上述指标构建预测TO的列线图模型,在训练集、测试集ROC曲线分析列线图模型预测患者术后达到TO的曲线下面积分别为0.875(95%CI:0.782~0.938)、0.860(95%CI:0.767~0.912),校准曲线与标准曲线基本一致,表示模型具有良好的预测能力;决策曲线分析显示,在多数阈值下(0.1~0.8)模型均具有良好的临床净获益。结论基于术前HSP90α、LMR建立的列线图模型在预测肝内胆管癌患者术后实现TO方面准确度和临床适用性均较好,可为临床治疗提供参考。

Objective To construct a predictive model based on preoperative heat shock protein 90 alpha(HSP90 alpha)and lymphocyte count/monocyte ratio(LMR),for prediction of the textbook outcome(TO)of intrahepatic cholangiocarcinoma after surgery,and evaluate the predictive value of the model.Methods Retrospective analysis of data from 210 patients with intrahepatic cholangiocarcinoma admitted to Chengde Central Hospital from January 2022 to December 2023,including 122 males and 88 females,aged(61.3±5.5)years.The patients were randomly divided into a training set(147 cases)and a validation set(63 cases)according to a ratio of 7:3.According to whether the patients achieved TO after surgery,the patients in the training set were divided into a TO group(n=39)and a non-TO group(n=108).The conditions of tumor length<5 cm,lymph node metastasis,large vessel invasion,preoperative HSP90αdecrease,and preoperative LMR increase were compared between the two groups.Based on the training set,univariate and multivariate logistic regression were used to analyze the influencing factors of postoperative TO in patients with intrahepatic cholangiocarcinoma.Based on multi-factor results,R 4.3.0 software was used to construct a prediction model for TO.The model was evaluated by receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DSA).Results Multivariate logistic regression analysis showed that the tumor diameter<5 cm(OR=1.917,95%CI:1.104-4.024),no lymph node metastasis(OR=2.489,95%CI:1.030-3.619),and no invasion of large vessels(OR=2.565,95%CI:2.097-5.093),the decrease of HSP90αbefore surgery(OR=3.161,95%CI:2.536-5.358),and the increase of LMR before surgery(OR=2.088,95%CI:1.454-4.262)were the influencing factors for patients TO achieve postoperative TO(all P<0.05).A correlation nomogram model was built based on the above indicators.The area under the curve of the model predicting the postoperative TO of the patients in the training set and the test set were 0.875(95%CI:0.782-0.938)and 0.860(95%CI:0.767-0.912),respectively,indicating good predictive value of the model.The calibration curve was basically consistent with the standard curve,indicating that the model has good consistency and accuracy.DCA results showed that the models had good clinical net benefit in the threshold probability range of 0.1~0.8.Conclusion The nomogram model based on perioperative HSP90αand LMR has good accuracy and clinical applicability in predicting the possibility of achieving TO after surgery for cholangiocarcinoma,which can provide a reference for clinical treatment.