Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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
_version_ 1784806024123777024
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
work_keys_str_mv AT liuyanli cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT liangwanmei cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT changyabin cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT hezehui cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT wumeijian cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT zhenghaozhi cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT kexinrong cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT lvminjia cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT liuqingqian cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT liuqinyu cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT tangwaner cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT huangqiaoling cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT luyu cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT hemin cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT yangqijun cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT mochunpan cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT wangjiefan cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT pengkunwei cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT minzhiqun cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT suhang cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma
AT chenjingqi cep192isanovelprognosticmarkerandcorrelateswiththeimmunemicroenvironmentinhepatocellularcarcinoma