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Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis

We aimed to explore the tumor mutational burden (TMB) and immune infiltration in HCC and investigate new biomarkers for immunotherapy. Transcriptome and gene mutation data were downloaded from the GDC portal, including 374 HCC samples and 50 matched normal samples. Furthermore, we divided the sample...

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Autores principales: Yin, Lu, Zhou, Liuzhi, Xu, Rujun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928364/
https://www.ncbi.nlm.nih.gov/pubmed/33681288
http://dx.doi.org/10.3389/fmolb.2020.599142
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author Yin, Lu
Zhou, Liuzhi
Xu, Rujun
author_facet Yin, Lu
Zhou, Liuzhi
Xu, Rujun
author_sort Yin, Lu
collection PubMed
description We aimed to explore the tumor mutational burden (TMB) and immune infiltration in HCC and investigate new biomarkers for immunotherapy. Transcriptome and gene mutation data were downloaded from the GDC portal, including 374 HCC samples and 50 matched normal samples. Furthermore, we divided the samples into high and low TMB groups, and analyzed the differential genes between them with GO, KEGG, and GSEA. Cibersort was used to assess the immune cell infiltration in the samples. Finally, univariate and multivariate Cox regression analyses were performed to identify differential genes related to TMB and immune infiltration, and a risk prediction model was constructed. We found 10 frequently mutated genes, including TP53, TTN, CTNNB1, MUC16, ALB, PCLO, MUC, APOB, RYR2, and ABCA. Pathway analysis indicated that these TMB-related differential genes were mainly enriched in PI3K-AKT. Cibersort analysis showed that memory B cells (p = 0.02), CD8+ T cells (p = 0.09), CD4+ memory activated T cells (p = 0.07), and neutrophils (p = 0.06) demonstrated a difference in immune infiltration between high and low TMB groups. On multivariate analysis, GABRA3 (p = 0.05), CECR7 (p < 0.001), TRIM16 (p = 0.003), and IL7R (p = 0.04) were associated with TMB and immune infiltration. The risk prediction model had an area under the curve (AUC) of 0.69, suggesting that patients with low risk had better survival outcomes. Our study demonstrated for the first time that CECR7, GABRA3, IL7R, and TRIM16L were associated with TMB and promoted antitumor immunity in HCC.
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spelling pubmed-79283642021-03-04 Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis Yin, Lu Zhou, Liuzhi Xu, Rujun Front Mol Biosci Molecular Biosciences We aimed to explore the tumor mutational burden (TMB) and immune infiltration in HCC and investigate new biomarkers for immunotherapy. Transcriptome and gene mutation data were downloaded from the GDC portal, including 374 HCC samples and 50 matched normal samples. Furthermore, we divided the samples into high and low TMB groups, and analyzed the differential genes between them with GO, KEGG, and GSEA. Cibersort was used to assess the immune cell infiltration in the samples. Finally, univariate and multivariate Cox regression analyses were performed to identify differential genes related to TMB and immune infiltration, and a risk prediction model was constructed. We found 10 frequently mutated genes, including TP53, TTN, CTNNB1, MUC16, ALB, PCLO, MUC, APOB, RYR2, and ABCA. Pathway analysis indicated that these TMB-related differential genes were mainly enriched in PI3K-AKT. Cibersort analysis showed that memory B cells (p = 0.02), CD8+ T cells (p = 0.09), CD4+ memory activated T cells (p = 0.07), and neutrophils (p = 0.06) demonstrated a difference in immune infiltration between high and low TMB groups. On multivariate analysis, GABRA3 (p = 0.05), CECR7 (p < 0.001), TRIM16 (p = 0.003), and IL7R (p = 0.04) were associated with TMB and immune infiltration. The risk prediction model had an area under the curve (AUC) of 0.69, suggesting that patients with low risk had better survival outcomes. Our study demonstrated for the first time that CECR7, GABRA3, IL7R, and TRIM16L were associated with TMB and promoted antitumor immunity in HCC. Frontiers Media S.A. 2021-02-16 /pmc/articles/PMC7928364/ /pubmed/33681288 http://dx.doi.org/10.3389/fmolb.2020.599142 Text en Copyright © 2021 Yin, Zhou and Xu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Yin, Lu
Zhou, Liuzhi
Xu, Rujun
Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis
title Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis
title_full Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis
title_fullStr Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis
title_full_unstemmed Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis
title_short Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis
title_sort identification of tumor mutation burden and immune infiltrates in hepatocellular carcinoma based on multi-omics analysis
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928364/
https://www.ncbi.nlm.nih.gov/pubmed/33681288
http://dx.doi.org/10.3389/fmolb.2020.599142
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AT xurujun identificationoftumormutationburdenandimmuneinfiltratesinhepatocellularcarcinomabasedonmultiomicsanalysis