肿瘤突变负荷在评价肝细胞癌预后中的价值和应用  

Prognostic value of tumor mutation burden in hepatocellular carcinoma

作　　者：刘凤悦[1] 宋建平 王亚栋 刘炎锋[3] LIU Feng-yue;SONG Jian-ping;WANG Ya-dong;LIU Yan-feng(Department of Organ Transplantation,Qilu Hospital of Shandong University,Jinan 250012,China;Department of Hepatobiliary Surgery,The Second Hospital of Shandong University,Jinan 250033,China;Department of Hepatobiliary Surgery,Qilu Hospital of Shandong University,Jinan 250012,China)

机构地区：[1]山东大学齐鲁医院器官移植科,山东济南250012 [2]山东大学第二医院肝胆外科,山东济南250033 [3]山东大学齐鲁医院肝胆外科,山东济南250012

出　　处：《中国现代普通外科进展》2023年第2期111-115,共5页Chinese Journal of Current Advances in General Surgery

基　　金：山东省自然科学基金面上项目(ZR2021MH339)。

摘　　要：目的:探讨肿瘤突变负荷(TMB)在评价肝细胞癌(HCC)预后中的价值,并建立应用模型。方法:纳入HCC患者107例,根据时间依赖性受试者工作特性(ROC)曲线及曲线下面积(AUC)确定TMB截断值。Cox回归分析TMB与总生存期(OS)的相关性。Kaplan-Meier法构建生存曲线,根据Cox回归分析结果构建列线图预后预测模型,通过校准曲线和决策曲线分析(DCA)验证列线图模型的可靠性。结果:根据时间依赖性ROC曲线和AUC确定TMB最佳截断值为3.3 mut/Mb。Kaplan-Meier结果显示,TMB高的患者OS较差[HR=1.68(1.09,2.59),P=0.020];Cox多因素回归分析结果显示,TMB是HCC的独立预后因子[HR=1.81(1.14,2.87),P=0.011]。将HCC独立预后因子(微血管侵犯、肿瘤转移、TMB)纳入列线图预后预测模型的构建,一致性指数为0.692(0.661,0.724),校准曲线和DCA证实预后预测模型准确性良好。结论:TMB是HCC的独立预后因子,高TMB患者预后较差;以TMB等独立预后因子建立的预后预测模型准确性良好,有较高的临床应用价值。Objective:To investigate the prognostic value of tumor mutation burden(TMB)in hepatocellular carcinoma(HCC)and build an application model.Methods:Data of 107 HCC patients was included in the study.The cut-off value of TMB was determined according to the time dependent receiver operator characteristic(ROC)curve and area under the curve(AUC).Cox regression analysis was used to detect the correlation between TMB and the overall survival time(OS)of patients.Kaplan-Meier method was used to construct the survival curve.The nomogram prognosis prediction model was constructed according to the Cox regression analysis results and the reliability of the nomogram model was verified through the analysis of calibration curve and Decision Curve Analysis(DCA).Results:According to the time dependent ROC curve and AUC,the optimal truncation value of TMB was determined to be 3.3 mut/Mb.Kaplan-Meier curve showed that patients with high TMB had a poor OS(Hazard Ratio=1.68(1.09,2.59),P=0.020).Multivariate Cox regression analysis indicated that TMB was an independent prognostic factor of HCC(HR=1.81(1.14,2.87),P=0.011).According to the results of Cox multivariate regression analysis,the independent prognostic factors of HCC(microvascular invasion,tumor metastasis,TMB)were included in the construction of the nomogram prognosis prediction model(consistency index 0.692(0.66,0.724)).The calibration curve and DCA proved the accuracy of the prognosis prediction model.Conclusion:TMB was an independent prognostic factor of HCC,and the prognosis of patients with high TMB was poor.The prognostic prediction model based on independent prognostic factors such as TMB has good accuracy and high clinical application value.

关 键 词：肝细胞癌 肿瘤突变负荷 预后 

分 类 号：R735.7[医药卫生—肿瘤]