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CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma
Hepatocellular carcinoma (HCC) responds poorly to standard chemotherapy or targeted therapy; hence, exploration for novel therapeutic targets is urgently needed. CEP192 protein is indispensable for centrosome amplification, which has been extensively characterized in both hematological malignancies...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551108/ https://www.ncbi.nlm.nih.gov/pubmed/36238304 http://dx.doi.org/10.3389/fimmu.2022.950884 |
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author | Liu, Yanli Liang, Wanmei Chang, Yabin He, Zehui Wu, Meijian Zheng, Haozhi Ke, Xinrong Lv, Minjia Liu, Qingqian Liu, Qinyu Tang, Waner Huang, Qiaoling Lu, Yu He, Min Yang, Qijun Mo, Chunpan Wang, Jiefan Peng, Kunwei Min, Zhiqun Su, Hang Chen, Jingqi |
author_facet | Liu, Yanli Liang, Wanmei Chang, Yabin He, Zehui Wu, Meijian Zheng, Haozhi Ke, Xinrong Lv, Minjia Liu, Qingqian Liu, Qinyu Tang, Waner Huang, Qiaoling Lu, Yu He, Min Yang, Qijun Mo, Chunpan Wang, Jiefan Peng, Kunwei Min, Zhiqun Su, Hang Chen, Jingqi |
author_sort | Liu, Yanli |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) responds poorly to standard chemotherapy or targeted therapy; hence, exploration for novel therapeutic targets is urgently needed. CEP192 protein is indispensable for centrosome amplification, which has been extensively characterized in both hematological malignancies and solid tumors. Here, we combined bioinformatics and experimental approaches to assess the potential of CEP192 as a prognostic and therapeutic target in HCC. CEP192 expression increased with tumor stage and was associated with poor clinicopathologic features, frequent recurrence, and higher mortality. Upon single-cell RNA sequencing, CEP192 was found to be involved in the proliferation and self-renewal of hepatic progenitor-like cells. This observation was further evidenced using CEP192 silencing, which prevented tumor cell proliferation and self-renewal by arresting cells in the G0/G1 phase of the cell cycle. Notably, CEP192 was highly correlated with multiple tumor-associated cytokine ligand–receptor axes, including IL11–IL11RA, IL6–IL6R, and IL13–IL13RA1, which could promote interactions between hepatic progenitor-like cells, PLVAP+ endothelial cells, tumor-associated macrophages, and CD4+ T cells. Consequently, CEP192 expression was closely associated with an immunosuppressive tumor microenvironment and low immunophenoscores, making it a potential predictor of response to immune checkpoint inhibitors. Taken together, our results unravel a novel onco-immunological role of CEP192 in establishing the immunosuppressive tumor microenvironment and provide a novel biomarker, as well as a potential target for therapeutic intervention of HCC. |
format | Online Article Text |
id | pubmed-9551108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95511082022-10-12 CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma Liu, Yanli Liang, Wanmei Chang, Yabin He, Zehui Wu, Meijian Zheng, Haozhi Ke, Xinrong Lv, Minjia Liu, Qingqian Liu, Qinyu Tang, Waner Huang, Qiaoling Lu, Yu He, Min Yang, Qijun Mo, Chunpan Wang, Jiefan Peng, Kunwei Min, Zhiqun Su, Hang Chen, Jingqi Front Immunol Immunology Hepatocellular carcinoma (HCC) responds poorly to standard chemotherapy or targeted therapy; hence, exploration for novel therapeutic targets is urgently needed. CEP192 protein is indispensable for centrosome amplification, which has been extensively characterized in both hematological malignancies and solid tumors. Here, we combined bioinformatics and experimental approaches to assess the potential of CEP192 as a prognostic and therapeutic target in HCC. CEP192 expression increased with tumor stage and was associated with poor clinicopathologic features, frequent recurrence, and higher mortality. Upon single-cell RNA sequencing, CEP192 was found to be involved in the proliferation and self-renewal of hepatic progenitor-like cells. This observation was further evidenced using CEP192 silencing, which prevented tumor cell proliferation and self-renewal by arresting cells in the G0/G1 phase of the cell cycle. Notably, CEP192 was highly correlated with multiple tumor-associated cytokine ligand–receptor axes, including IL11–IL11RA, IL6–IL6R, and IL13–IL13RA1, which could promote interactions between hepatic progenitor-like cells, PLVAP+ endothelial cells, tumor-associated macrophages, and CD4+ T cells. Consequently, CEP192 expression was closely associated with an immunosuppressive tumor microenvironment and low immunophenoscores, making it a potential predictor of response to immune checkpoint inhibitors. Taken together, our results unravel a novel onco-immunological role of CEP192 in establishing the immunosuppressive tumor microenvironment and provide a novel biomarker, as well as a potential target for therapeutic intervention of HCC. Frontiers Media S.A. 2022-09-27 /pmc/articles/PMC9551108/ /pubmed/36238304 http://dx.doi.org/10.3389/fimmu.2022.950884 Text en Copyright © 2022 Liu, Liang, Chang, He, Wu, Zheng, Ke, Lv, Liu, Liu, Tang, Huang, Lu, He, Yang, Mo, Wang, Peng, Min, Su and Chen 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 | Immunology Liu, Yanli Liang, Wanmei Chang, Yabin He, Zehui Wu, Meijian Zheng, Haozhi Ke, Xinrong Lv, Minjia Liu, Qingqian Liu, Qinyu Tang, Waner Huang, Qiaoling Lu, Yu He, Min Yang, Qijun Mo, Chunpan Wang, Jiefan Peng, Kunwei Min, Zhiqun Su, Hang Chen, Jingqi CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma |
title | CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma |
title_full | CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma |
title_fullStr | CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma |
title_full_unstemmed | CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma |
title_short | CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma |
title_sort | cep192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551108/ https://www.ncbi.nlm.nih.gov/pubmed/36238304 http://dx.doi.org/10.3389/fimmu.2022.950884 |
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