Cargando…

Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC

Hepatocellular carcinoma (HCC) is a common malignancy with higher mortality, and means are urgently needed to improve the prognosis. T cell exclusion (TCE) plays a pivotal role in immune evasion, and lncRNAs represent a large group of tumor development and progression modulators. Using the TCGA HCC...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Xiawei, Zhang, Zhiqian, Liu, Mingcheng, Fu, Xing, A, Jun, Chen, Guoan, Wu, Shian, Dong, Jin-Tang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097819/
https://www.ncbi.nlm.nih.gov/pubmed/35572559
http://dx.doi.org/10.3389/fimmu.2022.880288
_version_ 1784706249293561856
author Li, Xiawei
Zhang, Zhiqian
Liu, Mingcheng
Fu, Xing
A, Jun
Chen, Guoan
Wu, Shian
Dong, Jin-Tang
author_facet Li, Xiawei
Zhang, Zhiqian
Liu, Mingcheng
Fu, Xing
A, Jun
Chen, Guoan
Wu, Shian
Dong, Jin-Tang
author_sort Li, Xiawei
collection PubMed
description Hepatocellular carcinoma (HCC) is a common malignancy with higher mortality, and means are urgently needed to improve the prognosis. T cell exclusion (TCE) plays a pivotal role in immune evasion, and lncRNAs represent a large group of tumor development and progression modulators. Using the TCGA HCC dataset (n=374), we identified 2752 differentially expressed and 702 TCE-associated lncRNAs, of which 336 were in both groups. As identified using the univariate Cox regression analysis, those associated with overall survival (OS) were subjected to the LASSO-COX regression analysis to develop a prognosis signature. The model, which consisted of 11 lncRNAs and was named 11LNCPS for 11-lncRNA prognosis signature, was validated and performed better than two previous models. In addition to OS and TCE, higher 11LNCPS scores had a significant correlation with reduced infiltrations of CD8+ T cells and dendritic cells (DCs) and decreased infiltrations of Th1, Th2, and pro B cells. As expected, these infiltration alterations were significantly associated with worse OS in HCC. Analysis of published data indicates that HCCs with higher 11LNCPS scores were transcriptomically similar to those that responded better to PDL1 inhibitor. Of the 11LNCPS lncRNAs, LINC01134 and AC116025.2 seem more crucial, as their upregulations affected more immune cell types’ infiltrations and were significantly associated with TCE, worse OS, and compromised immune responses in HCC. LncRNAs in the 11LNCPS impacted many cancer-associated biological processes and signaling pathways, particularly those involved in immune function and metabolism. The 11LNCPS should be useful for predicting prognosis and immune responses in HCC.
format Online
Article
Text
id pubmed-9097819
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-90978192022-05-13 Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC Li, Xiawei Zhang, Zhiqian Liu, Mingcheng Fu, Xing A, Jun Chen, Guoan Wu, Shian Dong, Jin-Tang Front Immunol Immunology Hepatocellular carcinoma (HCC) is a common malignancy with higher mortality, and means are urgently needed to improve the prognosis. T cell exclusion (TCE) plays a pivotal role in immune evasion, and lncRNAs represent a large group of tumor development and progression modulators. Using the TCGA HCC dataset (n=374), we identified 2752 differentially expressed and 702 TCE-associated lncRNAs, of which 336 were in both groups. As identified using the univariate Cox regression analysis, those associated with overall survival (OS) were subjected to the LASSO-COX regression analysis to develop a prognosis signature. The model, which consisted of 11 lncRNAs and was named 11LNCPS for 11-lncRNA prognosis signature, was validated and performed better than two previous models. In addition to OS and TCE, higher 11LNCPS scores had a significant correlation with reduced infiltrations of CD8+ T cells and dendritic cells (DCs) and decreased infiltrations of Th1, Th2, and pro B cells. As expected, these infiltration alterations were significantly associated with worse OS in HCC. Analysis of published data indicates that HCCs with higher 11LNCPS scores were transcriptomically similar to those that responded better to PDL1 inhibitor. Of the 11LNCPS lncRNAs, LINC01134 and AC116025.2 seem more crucial, as their upregulations affected more immune cell types’ infiltrations and were significantly associated with TCE, worse OS, and compromised immune responses in HCC. LncRNAs in the 11LNCPS impacted many cancer-associated biological processes and signaling pathways, particularly those involved in immune function and metabolism. The 11LNCPS should be useful for predicting prognosis and immune responses in HCC. Frontiers Media S.A. 2022-04-28 /pmc/articles/PMC9097819/ /pubmed/35572559 http://dx.doi.org/10.3389/fimmu.2022.880288 Text en Copyright © 2022 Li, Zhang, Liu, Fu, A, Chen, Wu and Dong 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, Xiawei
Zhang, Zhiqian
Liu, Mingcheng
Fu, Xing
A, Jun
Chen, Guoan
Wu, Shian
Dong, Jin-Tang
Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC
title Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC
title_full Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC
title_fullStr Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC
title_full_unstemmed Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC
title_short Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC
title_sort establishment of a lncrna-based prognostic gene signature associated with altered immune responses in hcc
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097819/
https://www.ncbi.nlm.nih.gov/pubmed/35572559
http://dx.doi.org/10.3389/fimmu.2022.880288
work_keys_str_mv AT lixiawei establishmentofalncrnabasedprognosticgenesignatureassociatedwithalteredimmuneresponsesinhcc
AT zhangzhiqian establishmentofalncrnabasedprognosticgenesignatureassociatedwithalteredimmuneresponsesinhcc
AT liumingcheng establishmentofalncrnabasedprognosticgenesignatureassociatedwithalteredimmuneresponsesinhcc
AT fuxing establishmentofalncrnabasedprognosticgenesignatureassociatedwithalteredimmuneresponsesinhcc
AT ajun establishmentofalncrnabasedprognosticgenesignatureassociatedwithalteredimmuneresponsesinhcc
AT chenguoan establishmentofalncrnabasedprognosticgenesignatureassociatedwithalteredimmuneresponsesinhcc
AT wushian establishmentofalncrnabasedprognosticgenesignatureassociatedwithalteredimmuneresponsesinhcc
AT dongjintang establishmentofalncrnabasedprognosticgenesignatureassociatedwithalteredimmuneresponsesinhcc