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LRP1B or TP53 mutations are associated with higher tumor mutational burden and worse survival in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the most leading causes of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have been proved to be beneficial for advanced HCC. Tumor mutational burden (TMB) is an important predictor for efficacy of ICIs. However, the genet...

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Autores principales: Wang, Longrong, Yan, Kai, He, Xigan, Zhu, Hongxu, Song, Jia, Chen, Shiqing, Cai, Shangli, Zhao, Yiming, Wang, Lu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738815/
https://www.ncbi.nlm.nih.gov/pubmed/33391418
http://dx.doi.org/10.7150/jca.48983
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author Wang, Longrong
Yan, Kai
He, Xigan
Zhu, Hongxu
Song, Jia
Chen, Shiqing
Cai, Shangli
Zhao, Yiming
Wang, Lu
author_facet Wang, Longrong
Yan, Kai
He, Xigan
Zhu, Hongxu
Song, Jia
Chen, Shiqing
Cai, Shangli
Zhao, Yiming
Wang, Lu
author_sort Wang, Longrong
collection PubMed
description Background: Hepatocellular carcinoma (HCC) is one of the most leading causes of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have been proved to be beneficial for advanced HCC. Tumor mutational burden (TMB) is an important predictor for efficacy of ICIs. However, the genetic landscape of Chinese HCC patients and the association between TMB and frequently mutated genes of HCC remain unclear. Methods: Whole-exome sequencing data of 369 liver tumors from the Cancer Genome Altas (TCGA) and next generation sequencing (NGS) data of 657 liver tumors from Chinese clinical dataset were included. Results: TP53 (61.8%) was the most frequently mutated gene in the Chinese cohort, followed by CTNNB1 (17.2%), RB1 (13.7%), and LRP1B (12.3%). The PI3K-Akt signaling (11.2%), the Rap1 signaling (8.1%), and Ras signaling (7.7%), were significantly mapped. LRP1B mutations were significantly associated with higher TMB in both TCGA cohort (P = 0.0003) and Chinese cohort (P = 0.0005). And TP53 mutations were also associated with higher TMB in the TCGA and Chinese cohort (P = 0.0005 and 0.0010, respectively). Prognosis analysis performed in TCGA cohort revealed LRP1B mutations were significantly associated with shorter overall survival (OS, median, 20.9 vs 61.7 months; HR, 2.22; P = 0.0012). TP53 mutation was an independent risk factor affecting both OS (HR 1.58, P = 0.0109) and PFS (HR 1.59, P = 0.0027). Conclusions: The results suggest that LRP1B or TP53 mutations are associated with higher TMB and a poor prognostic factor in HCC.
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spelling pubmed-77388152021-01-01 LRP1B or TP53 mutations are associated with higher tumor mutational burden and worse survival in hepatocellular carcinoma Wang, Longrong Yan, Kai He, Xigan Zhu, Hongxu Song, Jia Chen, Shiqing Cai, Shangli Zhao, Yiming Wang, Lu J Cancer Research Paper Background: Hepatocellular carcinoma (HCC) is one of the most leading causes of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have been proved to be beneficial for advanced HCC. Tumor mutational burden (TMB) is an important predictor for efficacy of ICIs. However, the genetic landscape of Chinese HCC patients and the association between TMB and frequently mutated genes of HCC remain unclear. Methods: Whole-exome sequencing data of 369 liver tumors from the Cancer Genome Altas (TCGA) and next generation sequencing (NGS) data of 657 liver tumors from Chinese clinical dataset were included. Results: TP53 (61.8%) was the most frequently mutated gene in the Chinese cohort, followed by CTNNB1 (17.2%), RB1 (13.7%), and LRP1B (12.3%). The PI3K-Akt signaling (11.2%), the Rap1 signaling (8.1%), and Ras signaling (7.7%), were significantly mapped. LRP1B mutations were significantly associated with higher TMB in both TCGA cohort (P = 0.0003) and Chinese cohort (P = 0.0005). And TP53 mutations were also associated with higher TMB in the TCGA and Chinese cohort (P = 0.0005 and 0.0010, respectively). Prognosis analysis performed in TCGA cohort revealed LRP1B mutations were significantly associated with shorter overall survival (OS, median, 20.9 vs 61.7 months; HR, 2.22; P = 0.0012). TP53 mutation was an independent risk factor affecting both OS (HR 1.58, P = 0.0109) and PFS (HR 1.59, P = 0.0027). Conclusions: The results suggest that LRP1B or TP53 mutations are associated with higher TMB and a poor prognostic factor in HCC. Ivyspring International Publisher 2021-01-01 /pmc/articles/PMC7738815/ /pubmed/33391418 http://dx.doi.org/10.7150/jca.48983 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Wang, Longrong
Yan, Kai
He, Xigan
Zhu, Hongxu
Song, Jia
Chen, Shiqing
Cai, Shangli
Zhao, Yiming
Wang, Lu
LRP1B or TP53 mutations are associated with higher tumor mutational burden and worse survival in hepatocellular carcinoma
title LRP1B or TP53 mutations are associated with higher tumor mutational burden and worse survival in hepatocellular carcinoma
title_full LRP1B or TP53 mutations are associated with higher tumor mutational burden and worse survival in hepatocellular carcinoma
title_fullStr LRP1B or TP53 mutations are associated with higher tumor mutational burden and worse survival in hepatocellular carcinoma
title_full_unstemmed LRP1B or TP53 mutations are associated with higher tumor mutational burden and worse survival in hepatocellular carcinoma
title_short LRP1B or TP53 mutations are associated with higher tumor mutational burden and worse survival in hepatocellular carcinoma
title_sort lrp1b or tp53 mutations are associated with higher tumor mutational burden and worse survival in hepatocellular carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738815/
https://www.ncbi.nlm.nih.gov/pubmed/33391418
http://dx.doi.org/10.7150/jca.48983
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