Retrospective Cohort Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 21, 2022; 10(3): 790-801
Published online Jan 21, 2022. doi: 10.12998/wjcc.v10.i3.790
High tumor mutation burden indicates a poor prognosis in patients with intrahepatic cholangiocarcinoma
Jian-Ping Song, Xue-Zhi Liu, Qian Chen, Yan-Feng Liu
Jian-Ping Song, Department of Organ Transplantation, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
Xue-Zhi Liu, Department of General Surgery, Shouguang People's Hospital, Shouguang 262700, Shandong Province, China
Qian Chen, Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
Yan-Feng Liu, Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: All the authors solely contributed to this paper.
Supported by Shandong Scientific and Technological Research Program, No. 2019GSF108254; and Shandong Natural Science Foundation, No. ZR2021MH339.
Institutional review board statement: Ethics approval and patient consent were waived by the MSKCC Institutional Review Board.
Informed consent statement: Informed consent from patients was waived by the MSKCC IRB per 45 CFR 46.116 and 45 CFR 164.512, since our data were retrieved from a public database.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The data that support the findings of this study are available in MSKCC (MSKCC cohort: http://www.cbioportal.org/study/summary?id=ihch_msk_2021)
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: 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/
Corresponding author: Yan-Feng Liu, FRSC, MD, PhD, Doctor, Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, No. 107 Wenhua Xi Road, Jinan 250012, Shandong Province, China. liu19822012@163.com
Received: August 17, 2021
Peer-review started: August 17, 2021
First decision: November 8, 2021
Revised: November 17, 2021
Accepted: December 23, 2021
Article in press: December 23, 2021
Published online: January 21, 2022
Abstract
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.

Keywords: Tumor mutation burden, Intrahepatic cholangiocarcinoma, Prognosis, Nomogram

Core Tip: We analyzed the data of 412 patients with intrahepatic cholangiocarcinoma (ICC) from the Memorial Sloan Kettering Cancer Center cohort in the study. ICC patients with high tumor mutation burden (TMB) indicated a poor overall survival (OS) and relapse free survival compared with those with those with low TMB. Cox regression analysis of patient OS also demonstrated that TMB was an independent risk predictor for ICC. The nomogram and calibration curve also indicated the effectiveness of the constructed prognostic model.