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ZCCHC17 Served as a Predictive Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the common malignant tumors. The prognosis and five-year survival rate of HCC are not promising due to tumor recurrence and metastasis. Exploring markers that contribute to the early diagnosis of HCC, markers for prognostic evaluation of HCC patients, and eff...

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Autores principales: Liu, Fahui, Liang, Jiadong, Long, Puze, Zhu, Lilan, Hou, Wanyun, Wu, Xueming, Luo, Chunying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770814/
https://www.ncbi.nlm.nih.gov/pubmed/35071004
http://dx.doi.org/10.3389/fonc.2021.799566
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author Liu, Fahui
Liang, Jiadong
Long, Puze
Zhu, Lilan
Hou, Wanyun
Wu, Xueming
Luo, Chunying
author_facet Liu, Fahui
Liang, Jiadong
Long, Puze
Zhu, Lilan
Hou, Wanyun
Wu, Xueming
Luo, Chunying
author_sort Liu, Fahui
collection PubMed
description Hepatocellular carcinoma (HCC) is one of the common malignant tumors. The prognosis and five-year survival rate of HCC are not promising due to tumor recurrence and metastasis. Exploring markers that contribute to the early diagnosis of HCC, markers for prognostic evaluation of HCC patients, and effective targets for treating HCC patients are in the spotlight of HCC therapy. Zinc Finger CCHC-Type Containing 17 (ZCCHC17) encodes the RNA binding protein ZCCHC17, but its role in HCC is still unclear. Here, 90 paraffin-embedded specimens combined with bioinformatics were used to comprehensively clarify the value of ZCCHC17 in the diagnosis and prognosis of HCC and its potential functions. Paraffin-embedded specimens were used to assess ZCCHC17 protein expression and its correlation with prognosis in 90 HCC patients. the public data sets of HCC patients from TCGA, ICG, and GEO databases were also used for further analysis. It was found that protein and mRNA levels of ZCCHC17 in HCC tissues were significantly higher than those in normal tissues. The abnormally high expression may be related to the abnormal DNA methylation of ZCCHC17 in tumor tissues. The high expression of ZCCHC17 is related to AFP, histologic grade, tumor status, vascular invasion, and pathological stage. Multi-data set analysis showed that patients with high ZCCHC17 expression had a worse prognosis, and multivariate cox regression analysis showed an independent prognostic significance of ZCCHC17. The results of functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), indicate that ZCCHC17 is mainly involved in immune regulation. Subsequently, further single-sample gene set enrichment analysis (ssGSEA) showed that the expression of ZCCHC17 was related to the infiltration of immune cells. Importantly, we also analyzed the relationship between ZCCHC17 and immune checkpoint genes, tumor mutation burden (TMB), microsatellite instability (MSI) and TP53 status in HCC patients and evaluated the role of ZCCHC17 in cancer immunotherapy. In summary, ZCCHC17 is a novel marker for the diagnosis and prognostic evaluation of HCC. Concurrently, it regulates immune cells in the tumor microenvironment (TME) of HCC patients, which has a specific reference value for the immunotherapy of HCC.
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spelling pubmed-87708142022-01-21 ZCCHC17 Served as a Predictive Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma Liu, Fahui Liang, Jiadong Long, Puze Zhu, Lilan Hou, Wanyun Wu, Xueming Luo, Chunying Front Oncol Oncology Hepatocellular carcinoma (HCC) is one of the common malignant tumors. The prognosis and five-year survival rate of HCC are not promising due to tumor recurrence and metastasis. Exploring markers that contribute to the early diagnosis of HCC, markers for prognostic evaluation of HCC patients, and effective targets for treating HCC patients are in the spotlight of HCC therapy. Zinc Finger CCHC-Type Containing 17 (ZCCHC17) encodes the RNA binding protein ZCCHC17, but its role in HCC is still unclear. Here, 90 paraffin-embedded specimens combined with bioinformatics were used to comprehensively clarify the value of ZCCHC17 in the diagnosis and prognosis of HCC and its potential functions. Paraffin-embedded specimens were used to assess ZCCHC17 protein expression and its correlation with prognosis in 90 HCC patients. the public data sets of HCC patients from TCGA, ICG, and GEO databases were also used for further analysis. It was found that protein and mRNA levels of ZCCHC17 in HCC tissues were significantly higher than those in normal tissues. The abnormally high expression may be related to the abnormal DNA methylation of ZCCHC17 in tumor tissues. The high expression of ZCCHC17 is related to AFP, histologic grade, tumor status, vascular invasion, and pathological stage. Multi-data set analysis showed that patients with high ZCCHC17 expression had a worse prognosis, and multivariate cox regression analysis showed an independent prognostic significance of ZCCHC17. The results of functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), indicate that ZCCHC17 is mainly involved in immune regulation. Subsequently, further single-sample gene set enrichment analysis (ssGSEA) showed that the expression of ZCCHC17 was related to the infiltration of immune cells. Importantly, we also analyzed the relationship between ZCCHC17 and immune checkpoint genes, tumor mutation burden (TMB), microsatellite instability (MSI) and TP53 status in HCC patients and evaluated the role of ZCCHC17 in cancer immunotherapy. In summary, ZCCHC17 is a novel marker for the diagnosis and prognostic evaluation of HCC. Concurrently, it regulates immune cells in the tumor microenvironment (TME) of HCC patients, which has a specific reference value for the immunotherapy of HCC. Frontiers Media S.A. 2022-01-06 /pmc/articles/PMC8770814/ /pubmed/35071004 http://dx.doi.org/10.3389/fonc.2021.799566 Text en Copyright © 2022 Liu, Liang, Long, Zhu, Hou, Wu and Luo 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
Liu, Fahui
Liang, Jiadong
Long, Puze
Zhu, Lilan
Hou, Wanyun
Wu, Xueming
Luo, Chunying
ZCCHC17 Served as a Predictive Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma
title ZCCHC17 Served as a Predictive Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma
title_full ZCCHC17 Served as a Predictive Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma
title_fullStr ZCCHC17 Served as a Predictive Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma
title_full_unstemmed ZCCHC17 Served as a Predictive Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma
title_short ZCCHC17 Served as a Predictive Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma
title_sort zcchc17 served as a predictive biomarker for prognosis and immunotherapy in hepatocellular carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770814/
https://www.ncbi.nlm.nih.gov/pubmed/35071004
http://dx.doi.org/10.3389/fonc.2021.799566
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