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Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment

BACKGROUND: The crucial role of DTL has been previously implicated in genomic stability; however, its prognostic value and its relation with tumor immunity in hepatocellular carcinoma (HCC) remain to be further explored. METHODS: Transcriptional and mutational datasets as well as clinical informatio...

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Autores principales: Li, Zuyin, Wang, Rangrang, Qiu, Chen, Cao, Can, Zhang, Jianming, Ge, Jun, Shi, Yuanping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980229/
https://www.ncbi.nlm.nih.gov/pubmed/35392073
http://dx.doi.org/10.3389/fimmu.2022.834606
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author Li, Zuyin
Wang, Rangrang
Qiu, Chen
Cao, Can
Zhang, Jianming
Ge, Jun
Shi, Yuanping
author_facet Li, Zuyin
Wang, Rangrang
Qiu, Chen
Cao, Can
Zhang, Jianming
Ge, Jun
Shi, Yuanping
author_sort Li, Zuyin
collection PubMed
description BACKGROUND: The crucial role of DTL has been previously implicated in genomic stability; however, its prognostic value and its relation with tumor immunity in hepatocellular carcinoma (HCC) remain to be further explored. METHODS: Transcriptional and mutational datasets as well as clinical information were retrieved from the GEO, ICGC, and TCGA databases. Differentially expressed genes (DEGs) were obtained from the comparison of DTL(high) and DTL(low) expression groups of the TCGA-HCC cohort. Those genes were under KEGG and gene ontology (GO) analyses to decipher the influence of the DTL gene on the biological behavior of HCC tumor cells. The survival status and mutational characteristics of patients according to DTL levels were depicted and analyzed. The DTL overexpression in HCC and its impact on prognosis were further confirmed by a cohort of 114 HCC patients (validation cohort). The TIMER, GEPIA, and TISIDB databases were adopted to investigate the potential relations between DTL levels and the status of immune cells, as well as immune cell infiltrations. RESULTS: The DTL gene is overexpressed in tumor tissues compared with distant non-malignant liver tissues, and DTL overexpression in HCC would enhance the HCC cells in the activities of cell cycle and division. HCC patients with high DTL expression have unfavorable clinical outcomes and harbor more somatic mutations than those with low DTL expression, and multivariate analysis also revealed that DTL overexpression could act as an independent biomarker for prognosis. Moreover, the DTL gene was positively linked to marker sets of infiltrating activated CD8+ and CD4+ T cells; however, these cells demonstrated to be functionally exhausted. CONCLUSIONS: Patients with a DTL overexpression phenotype in HCC have poorer prognosis than those in the DTL(low) group due to the role of the DTL gene in the process of pro-cell proliferation, accompanied by the immunosuppressive microenvironment and T cell exhaustion.
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spelling pubmed-89802292022-04-06 Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment Li, Zuyin Wang, Rangrang Qiu, Chen Cao, Can Zhang, Jianming Ge, Jun Shi, Yuanping Front Immunol Immunology BACKGROUND: The crucial role of DTL has been previously implicated in genomic stability; however, its prognostic value and its relation with tumor immunity in hepatocellular carcinoma (HCC) remain to be further explored. METHODS: Transcriptional and mutational datasets as well as clinical information were retrieved from the GEO, ICGC, and TCGA databases. Differentially expressed genes (DEGs) were obtained from the comparison of DTL(high) and DTL(low) expression groups of the TCGA-HCC cohort. Those genes were under KEGG and gene ontology (GO) analyses to decipher the influence of the DTL gene on the biological behavior of HCC tumor cells. The survival status and mutational characteristics of patients according to DTL levels were depicted and analyzed. The DTL overexpression in HCC and its impact on prognosis were further confirmed by a cohort of 114 HCC patients (validation cohort). The TIMER, GEPIA, and TISIDB databases were adopted to investigate the potential relations between DTL levels and the status of immune cells, as well as immune cell infiltrations. RESULTS: The DTL gene is overexpressed in tumor tissues compared with distant non-malignant liver tissues, and DTL overexpression in HCC would enhance the HCC cells in the activities of cell cycle and division. HCC patients with high DTL expression have unfavorable clinical outcomes and harbor more somatic mutations than those with low DTL expression, and multivariate analysis also revealed that DTL overexpression could act as an independent biomarker for prognosis. Moreover, the DTL gene was positively linked to marker sets of infiltrating activated CD8+ and CD4+ T cells; however, these cells demonstrated to be functionally exhausted. CONCLUSIONS: Patients with a DTL overexpression phenotype in HCC have poorer prognosis than those in the DTL(low) group due to the role of the DTL gene in the process of pro-cell proliferation, accompanied by the immunosuppressive microenvironment and T cell exhaustion. Frontiers Media S.A. 2022-03-22 /pmc/articles/PMC8980229/ /pubmed/35392073 http://dx.doi.org/10.3389/fimmu.2022.834606 Text en Copyright © 2022 Li, Wang, Qiu, Cao, Zhang, Ge and Shi 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
Li, Zuyin
Wang, Rangrang
Qiu, Chen
Cao, Can
Zhang, Jianming
Ge, Jun
Shi, Yuanping
Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment
title Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment
title_full Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment
title_fullStr Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment
title_full_unstemmed Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment
title_short Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment
title_sort role of dtl in hepatocellular carcinoma and its impact on the tumor microenvironment
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980229/
https://www.ncbi.nlm.nih.gov/pubmed/35392073
http://dx.doi.org/10.3389/fimmu.2022.834606
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