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Proteomic Analyses Identify Therapeutic Targets in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the fourth cause of cancer-related mortality worldwide. While many targeted therapies have been developed, the majority of HCC tumors do not harbor clinically actionable mutations. Protein-level aberrations, especially those not evident at the genomic level, present...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006883/ https://www.ncbi.nlm.nih.gov/pubmed/35433463 http://dx.doi.org/10.3389/fonc.2022.814120 |
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author | Elmas, Abdulkadir Lujambio, Amaia Huang, Kuan-lin |
author_facet | Elmas, Abdulkadir Lujambio, Amaia Huang, Kuan-lin |
author_sort | Elmas, Abdulkadir |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) is the fourth cause of cancer-related mortality worldwide. While many targeted therapies have been developed, the majority of HCC tumors do not harbor clinically actionable mutations. Protein-level aberrations, especially those not evident at the genomic level, present therapeutic opportunities but have rarely been systematically characterized in HCC. In this study, we performed proteogenomic analyses of 260 primary tumors from two HBV-related HCC patient cohorts with global mass-spectrometry (MS) proteomics data. Combining tumor-normal and inter-tumor analyses, we identified overexpressed targets including PDGFRB, FGFR4, ERBB2/3, CDK6 kinases and MFAP5, HMCN1, and Hsp proteins in HCC, many of which showed low frequencies of genomic and/or transcriptomic aberrations. Protein expression of FGFR4 kinase and Hsp proteins were significantly associated with response to their corresponding inhibitors. Our results provide a catalog of protein targets in HCC and demonstrate the potential of proteomics approaches in advancing precision medicine in cancer types lacking druggable mutations. |
format | Online Article Text |
id | pubmed-9006883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90068832022-04-14 Proteomic Analyses Identify Therapeutic Targets in Hepatocellular Carcinoma Elmas, Abdulkadir Lujambio, Amaia Huang, Kuan-lin Front Oncol Oncology Hepatocellular carcinoma (HCC) is the fourth cause of cancer-related mortality worldwide. While many targeted therapies have been developed, the majority of HCC tumors do not harbor clinically actionable mutations. Protein-level aberrations, especially those not evident at the genomic level, present therapeutic opportunities but have rarely been systematically characterized in HCC. In this study, we performed proteogenomic analyses of 260 primary tumors from two HBV-related HCC patient cohorts with global mass-spectrometry (MS) proteomics data. Combining tumor-normal and inter-tumor analyses, we identified overexpressed targets including PDGFRB, FGFR4, ERBB2/3, CDK6 kinases and MFAP5, HMCN1, and Hsp proteins in HCC, many of which showed low frequencies of genomic and/or transcriptomic aberrations. Protein expression of FGFR4 kinase and Hsp proteins were significantly associated with response to their corresponding inhibitors. Our results provide a catalog of protein targets in HCC and demonstrate the potential of proteomics approaches in advancing precision medicine in cancer types lacking druggable mutations. Frontiers Media S.A. 2022-03-30 /pmc/articles/PMC9006883/ /pubmed/35433463 http://dx.doi.org/10.3389/fonc.2022.814120 Text en Copyright © 2022 Elmas, Lujambio and Huang https://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 | Oncology Elmas, Abdulkadir Lujambio, Amaia Huang, Kuan-lin Proteomic Analyses Identify Therapeutic Targets in Hepatocellular Carcinoma |
title | Proteomic Analyses Identify Therapeutic Targets in Hepatocellular Carcinoma |
title_full | Proteomic Analyses Identify Therapeutic Targets in Hepatocellular Carcinoma |
title_fullStr | Proteomic Analyses Identify Therapeutic Targets in Hepatocellular Carcinoma |
title_full_unstemmed | Proteomic Analyses Identify Therapeutic Targets in Hepatocellular Carcinoma |
title_short | Proteomic Analyses Identify Therapeutic Targets in Hepatocellular Carcinoma |
title_sort | proteomic analyses identify therapeutic targets in hepatocellular carcinoma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006883/ https://www.ncbi.nlm.nih.gov/pubmed/35433463 http://dx.doi.org/10.3389/fonc.2022.814120 |
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