Cargando…

Construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro

BACKGROUND: The accumulation of single nucleotide variants (SNVs) and the emergence of neoantigens can affect tumour proliferation and the immune microenvironment. However, the SNV-related immune microenvironment characteristics and key genes involved in hepatocellular carcinoma (HCC) are still uncl...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Yu-Jie, He, Min-Ke, Liu, Shuang, Huang, Li-Chang, Bu, Xiao-Yun, Kan, Anna, Shi, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600893/
https://www.ncbi.nlm.nih.gov/pubmed/34794449
http://dx.doi.org/10.1186/s12935-021-02321-z
_version_ 1784601239863951360
author Xu, Yu-Jie
He, Min-Ke
Liu, Shuang
Huang, Li-Chang
Bu, Xiao-Yun
Kan, Anna
Shi, Ming
author_facet Xu, Yu-Jie
He, Min-Ke
Liu, Shuang
Huang, Li-Chang
Bu, Xiao-Yun
Kan, Anna
Shi, Ming
author_sort Xu, Yu-Jie
collection PubMed
description BACKGROUND: The accumulation of single nucleotide variants (SNVs) and the emergence of neoantigens can affect tumour proliferation and the immune microenvironment. However, the SNV-related immune microenvironment characteristics and key genes involved in hepatocellular carcinoma (HCC) are still unclear. We aimed to evaluate differences in the SNV-related immune microenvironment, construct a prognostic model and validate the key genes in vitro. METHODS: The categories of samples were defined by the expression of SNV score-related genes to evaluate the differences in mutational features, immune environment and prognosis. The survival model was constructed with survival-associated genes and verified in two independent test datasets. RCAN2, the key gene screened out for biofunction, was validated in vitro. RESULTS: IC2, among the three integrated clusters (IC1, IC2, IC3) classified by the 82 SNV score-related genes, was distinct from the rest in SNV score and immune cell infiltration, showing a better prognosis. Seven prognostic markers, HTRA3, GGT5, RCAN2, LGALS3, CXCL1, CLEC3B, and CTHRC1, were screened to construct a prognostic model. The survival model distinguished high-risk patients with poor prognoses in three independent datasets (log-rank P < 0.0001, 0.011, and 0.0068, respectively) with acceptable sensitivity and specificity. RCAN2 was inversely correlated with NK cell infiltration, and knockdown of RCAN2 promoted proliferation in HCC. CONCLUSIONS: This study revealed the characteristics of the HCC SNV-associated subgroup and screened seven latent markers for their accuracy of prognosis. Additionally, RCAN2 was preliminarily proven to influence proliferation in HCC and it had a close relationship with NK cell infiltration in vitro. With the capability to predict HCC outcomes, the model constructed with seven key differentially expressed genes offers new insights into individual therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02321-z.
format Online
Article
Text
id pubmed-8600893
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-86008932021-11-19 Construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro Xu, Yu-Jie He, Min-Ke Liu, Shuang Huang, Li-Chang Bu, Xiao-Yun Kan, Anna Shi, Ming Cancer Cell Int Primary Research BACKGROUND: The accumulation of single nucleotide variants (SNVs) and the emergence of neoantigens can affect tumour proliferation and the immune microenvironment. However, the SNV-related immune microenvironment characteristics and key genes involved in hepatocellular carcinoma (HCC) are still unclear. We aimed to evaluate differences in the SNV-related immune microenvironment, construct a prognostic model and validate the key genes in vitro. METHODS: The categories of samples were defined by the expression of SNV score-related genes to evaluate the differences in mutational features, immune environment and prognosis. The survival model was constructed with survival-associated genes and verified in two independent test datasets. RCAN2, the key gene screened out for biofunction, was validated in vitro. RESULTS: IC2, among the three integrated clusters (IC1, IC2, IC3) classified by the 82 SNV score-related genes, was distinct from the rest in SNV score and immune cell infiltration, showing a better prognosis. Seven prognostic markers, HTRA3, GGT5, RCAN2, LGALS3, CXCL1, CLEC3B, and CTHRC1, were screened to construct a prognostic model. The survival model distinguished high-risk patients with poor prognoses in three independent datasets (log-rank P < 0.0001, 0.011, and 0.0068, respectively) with acceptable sensitivity and specificity. RCAN2 was inversely correlated with NK cell infiltration, and knockdown of RCAN2 promoted proliferation in HCC. CONCLUSIONS: This study revealed the characteristics of the HCC SNV-associated subgroup and screened seven latent markers for their accuracy of prognosis. Additionally, RCAN2 was preliminarily proven to influence proliferation in HCC and it had a close relationship with NK cell infiltration in vitro. With the capability to predict HCC outcomes, the model constructed with seven key differentially expressed genes offers new insights into individual therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02321-z. BioMed Central 2021-11-18 /pmc/articles/PMC8600893/ /pubmed/34794449 http://dx.doi.org/10.1186/s12935-021-02321-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Xu, Yu-Jie
He, Min-Ke
Liu, Shuang
Huang, Li-Chang
Bu, Xiao-Yun
Kan, Anna
Shi, Ming
Construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro
title Construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro
title_full Construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro
title_fullStr Construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro
title_full_unstemmed Construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro
title_short Construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro
title_sort construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600893/
https://www.ncbi.nlm.nih.gov/pubmed/34794449
http://dx.doi.org/10.1186/s12935-021-02321-z
work_keys_str_mv AT xuyujie constructionofasinglenucleotidevariantscorerelatedgenebasedprognosticmodelinhepatocellularcarcinomaanalysisofmultiindependentdatabasesandvalidationinvitro
AT heminke constructionofasinglenucleotidevariantscorerelatedgenebasedprognosticmodelinhepatocellularcarcinomaanalysisofmultiindependentdatabasesandvalidationinvitro
AT liushuang constructionofasinglenucleotidevariantscorerelatedgenebasedprognosticmodelinhepatocellularcarcinomaanalysisofmultiindependentdatabasesandvalidationinvitro
AT huanglichang constructionofasinglenucleotidevariantscorerelatedgenebasedprognosticmodelinhepatocellularcarcinomaanalysisofmultiindependentdatabasesandvalidationinvitro
AT buxiaoyun constructionofasinglenucleotidevariantscorerelatedgenebasedprognosticmodelinhepatocellularcarcinomaanalysisofmultiindependentdatabasesandvalidationinvitro
AT kananna constructionofasinglenucleotidevariantscorerelatedgenebasedprognosticmodelinhepatocellularcarcinomaanalysisofmultiindependentdatabasesandvalidationinvitro
AT shiming constructionofasinglenucleotidevariantscorerelatedgenebasedprognosticmodelinhepatocellularcarcinomaanalysisofmultiindependentdatabasesandvalidationinvitro