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High tumor mutation burden indicates a poor prognosis in patients with intrahepatic cholangiocarcinoma
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 immunot...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790456/ https://www.ncbi.nlm.nih.gov/pubmed/35127895 http://dx.doi.org/10.12998/wjcc.v10.i3.790 |
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author | Song, Jian-Ping Liu, Xue-Zhi Chen, Qian Liu, Yan-Feng |
author_facet | Song, Jian-Ping Liu, Xue-Zhi Chen, Qian Liu, Yan-Feng |
author_sort | Song, Jian-Ping |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8790456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-87904562022-02-03 High tumor mutation burden indicates a poor prognosis in patients with intrahepatic cholangiocarcinoma Song, Jian-Ping Liu, Xue-Zhi Chen, Qian Liu, Yan-Feng World J Clin Cases Retrospective Cohort Study 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. Baishideng Publishing Group Inc 2022-01-21 2022-01-21 /pmc/articles/PMC8790456/ /pubmed/35127895 http://dx.doi.org/10.12998/wjcc.v10.i3.790 Text en ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/ |
spellingShingle | Retrospective Cohort Study Song, Jian-Ping Liu, Xue-Zhi Chen, Qian Liu, Yan-Feng High tumor mutation burden indicates a poor prognosis in patients with intrahepatic cholangiocarcinoma |
title | High tumor mutation burden indicates a poor prognosis in patients with intrahepatic cholangiocarcinoma |
title_full | High tumor mutation burden indicates a poor prognosis in patients with intrahepatic cholangiocarcinoma |
title_fullStr | High tumor mutation burden indicates a poor prognosis in patients with intrahepatic cholangiocarcinoma |
title_full_unstemmed | High tumor mutation burden indicates a poor prognosis in patients with intrahepatic cholangiocarcinoma |
title_short | High tumor mutation burden indicates a poor prognosis in patients with intrahepatic cholangiocarcinoma |
title_sort | high tumor mutation burden indicates a poor prognosis in patients with intrahepatic cholangiocarcinoma |
topic | Retrospective Cohort Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790456/ https://www.ncbi.nlm.nih.gov/pubmed/35127895 http://dx.doi.org/10.12998/wjcc.v10.i3.790 |
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