BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is malignancies of the biliary duct system and constitutes approximately 10%-20%of all primary liver cancers.Tumor mutation burden(TMB)is a useful biomarker across many c...BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is malignancies of the biliary duct system and constitutes approximately 10%-20%of all primary liver cancers.Tumor mutation burden(TMB)is a useful biomarker across many cancer types for the identification of patients who will benefit from immunotherapy.Despite the role of TMB in calculating the effectiveness and prognosis of immune checkpoint inhibitors has been confirmed in multiple human cancer types,the prognostic value of TMB in ICC patients is rare investigated.AIM To investigate the prognostic value of TMB in patients with ICC.METHODS Data of 412 patients with ICC were included in the study.TMB was calculated as the total number of somatic non-silent protein-coding mutations divided by the coding region.The Kaplan-Meier method was used to analyze overall survival(OS),and relapse free survival(RFS).The cut-off value of TMB was determined by time-dependent receiver operating characteristic(ROC)curve.Cox regression was performed for multivariable analysis of OS.The nomogram and calibration curve were analyzed to construct and evaluate the prognostic model.RESULTS In the analysis of the time-dependent ROC curve,we defined 3.1 mut/Mb as the cut-off value of TMB.The Kaplan-Meier plot revealed that patients with high TMB had poor OS(HR=1.47,P=0.002)and RFS(HR=1.42,P=0.035).Cox regression analysis also demonstrated that TMB was an independent risk predictor for ICC(HR=1.43,P=0.0240).Furthermore,independent prognostic factors of ICC included CA19-9(HR=1.78,P=0.0005),chronic viral hepatitis(HR=1.72,P=0.0468),tumor resection(HR=2.58,P<0.0001)and disease progression(metastatic disease vs.solitary liver tumor;HR=2.55,P=0.0002).The nomogram and calibration curve also indicated the effectiveness of the constructed prognostic model.CONCLUSION TMB was an independent prognostic biomarker in patients with ICC.Moreover,patients with ICC with high TMB had poor OS and RFS as compared to those with low TMB.展开更多
BACKGROUND Diffuse reduction of spleen density(DROSD)is related to cancer prognosis;however,its role in intrahepatic cholangiocarcinoma(ICC)remains unclear.AIM To assess the predictive value of DROSD in the prognosis ...BACKGROUND Diffuse reduction of spleen density(DROSD)is related to cancer prognosis;however,its role in intrahepatic cholangiocarcinoma(ICC)remains unclear.AIM To assess the predictive value of DROSD in the prognosis of ICC after curative resection.METHODS In this multicenter retrospective cohort study,we enrolled patients with ICC who underwent curative hepatectomy between 2012 and 2019.Preoperative spleen density was measured using computed tomography.Overall survival(OS)and recurrence-free survival(RFS)rates were calculated and compared utilizing the Kaplan-Meier method.Univariable and multivariable Cox regression analyses were applied to identify independent factors for OS and RFS.A nomogram was created with independent risk factors to predict prognosis of patients with ICC.RESULTS One hundred and sixty-seven ICC patients were enrolled.Based on the diagnostic cut-off values(spleen density≤45.5 Hounsfield units),55(32.9%)patients had DROSD.Kaplan-Meier analysis indicated that patients with DROSD had worse OS and RFS than those without DROSD(P<0.05).Cox regression analysis revealed that DROSD,carcinoembryonic antigen level,carbohydrate antigen 19-9 level,length of hospital stay,lymph node metastasis,and postoperative complications were independent predictors for OS(P<0.05).The nomogram created with these factors was able to predict the prognosis of patients with ICC with good reliability(OS C-index=0.733).The area under the curve for OS was 0.79.CONCLUSION ICC patients with DROSD have worse OS and RFS.The nomogram is a simple and practical method to identify high-risk ICC patients with poor prognosis.展开更多
基金Supported by Shandong Scientific and Technological Research Program,No.2019GSF108254and Shandong Natural Science Foundation,No.ZR2021MH339.
文摘BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is malignancies of the biliary duct system and constitutes approximately 10%-20%of all primary liver cancers.Tumor mutation burden(TMB)is a useful biomarker across many cancer types for the identification of patients who will benefit from immunotherapy.Despite the role of TMB in calculating the effectiveness and prognosis of immune checkpoint inhibitors has been confirmed in multiple human cancer types,the prognostic value of TMB in ICC patients is rare investigated.AIM To investigate the prognostic value of TMB in patients with ICC.METHODS Data of 412 patients with ICC were included in the study.TMB was calculated as the total number of somatic non-silent protein-coding mutations divided by the coding region.The Kaplan-Meier method was used to analyze overall survival(OS),and relapse free survival(RFS).The cut-off value of TMB was determined by time-dependent receiver operating characteristic(ROC)curve.Cox regression was performed for multivariable analysis of OS.The nomogram and calibration curve were analyzed to construct and evaluate the prognostic model.RESULTS In the analysis of the time-dependent ROC curve,we defined 3.1 mut/Mb as the cut-off value of TMB.The Kaplan-Meier plot revealed that patients with high TMB had poor OS(HR=1.47,P=0.002)and RFS(HR=1.42,P=0.035).Cox regression analysis also demonstrated that TMB was an independent risk predictor for ICC(HR=1.43,P=0.0240).Furthermore,independent prognostic factors of ICC included CA19-9(HR=1.78,P=0.0005),chronic viral hepatitis(HR=1.72,P=0.0468),tumor resection(HR=2.58,P<0.0001)and disease progression(metastatic disease vs.solitary liver tumor;HR=2.55,P=0.0002).The nomogram and calibration curve also indicated the effectiveness of the constructed prognostic model.CONCLUSION TMB was an independent prognostic biomarker in patients with ICC.Moreover,patients with ICC with high TMB had poor OS and RFS as compared to those with low TMB.
基金Supported by National Natural Science Foundation of China,No.82072685the Science and Technology Innovation Program for College Students in Zhejiang Province,No.2020R413022.
文摘BACKGROUND Diffuse reduction of spleen density(DROSD)is related to cancer prognosis;however,its role in intrahepatic cholangiocarcinoma(ICC)remains unclear.AIM To assess the predictive value of DROSD in the prognosis of ICC after curative resection.METHODS In this multicenter retrospective cohort study,we enrolled patients with ICC who underwent curative hepatectomy between 2012 and 2019.Preoperative spleen density was measured using computed tomography.Overall survival(OS)and recurrence-free survival(RFS)rates were calculated and compared utilizing the Kaplan-Meier method.Univariable and multivariable Cox regression analyses were applied to identify independent factors for OS and RFS.A nomogram was created with independent risk factors to predict prognosis of patients with ICC.RESULTS One hundred and sixty-seven ICC patients were enrolled.Based on the diagnostic cut-off values(spleen density≤45.5 Hounsfield units),55(32.9%)patients had DROSD.Kaplan-Meier analysis indicated that patients with DROSD had worse OS and RFS than those without DROSD(P<0.05).Cox regression analysis revealed that DROSD,carcinoembryonic antigen level,carbohydrate antigen 19-9 level,length of hospital stay,lymph node metastasis,and postoperative complications were independent predictors for OS(P<0.05).The nomogram created with these factors was able to predict the prognosis of patients with ICC with good reliability(OS C-index=0.733).The area under the curve for OS was 0.79.CONCLUSION ICC patients with DROSD have worse OS and RFS.The nomogram is a simple and practical method to identify high-risk ICC patients with poor prognosis.
