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A novel prognostic biomarker: GINS3 is correlated with methylation and immune escape in liver hepatocellular carcinoma
BACKGROUND: Liver cancer remains one of the tricky malignancies nowadays. GINS complex subunit 3 (GINS3), part of the GINS tetrameric complex, is significantly upregulated in many cancers, including liver hepatocellular carcinoma (LIHC). With the development of liver cancer treatment, immune and mol...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10248566/ https://www.ncbi.nlm.nih.gov/pubmed/37304536 http://dx.doi.org/10.21037/tcr-22-2565 |
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author | Lai, Tianqi Peng, Tianqi Li, Jinying Jiang, Yuchuan Liu, Kangshou Yu, Wei Yao, Nan Hu, Youzhu Cao, Mingrong Liang, Junjie |
author_facet | Lai, Tianqi Peng, Tianqi Li, Jinying Jiang, Yuchuan Liu, Kangshou Yu, Wei Yao, Nan Hu, Youzhu Cao, Mingrong Liang, Junjie |
author_sort | Lai, Tianqi |
collection | PubMed |
description | BACKGROUND: Liver cancer remains one of the tricky malignancies nowadays. GINS complex subunit 3 (GINS3), part of the GINS tetrameric complex, is significantly upregulated in many cancers, including liver hepatocellular carcinoma (LIHC). With the development of liver cancer treatment, immune and molecular targeted therapy gradually becomes a promising treatment. However, the key target for liver cancer is still indistinct. Herein, the underneath mechanism of GINS3 was investigated to verify its role as a biomarker in LIHC. METHODS: Genomic expression, genetic alteration, and methylation analyses were obtained from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), The University of Alabama at Birmingham CANcer (UALCN), and Human Protein Atlas (HPA), cBioPortal, and MethSurv databases. Subsequently, the diagnostic and prognostic role of GINS3 in LIHC were analyzed based on data from receiver operating characteristic (ROC), Kaplan-Meier plotter (KM-plotter), and univariate and multivariate cox regression analyses. The functional analyses were conducted with GeneMANIA and STRING databases, gene-gene, and protein-protein interaction (PPI) networks, Gene Ontology (GO) term, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Tumor Immune Estimation Resource (TIMER), Tumor-Immune System Interaction Database (TISIDB), and Gene Expression Profiling Interactive Analysis (GEPIA) were utilized to explore the internal connection with the immune escape. RESULTS: Through the analyses of genomic expression, GINS3 was significantly upregulated in LIHC and positively correlated with higher T classification. ROC analysis indicated GINS3 as a potential biomarker in the diagnosis of LIHC. KM-plotter, univariate and multivariate cox regression analyses both associated GINS3 with poor prognosis in LIHC patients. GINS3 genetic alteration, gene-gene interaction, PPI networks, and enrichment analysis further revealed that GINS3 played a pivotal role in the progression of LIHC. Furthermore, hypermethylation of GINS3 at different cytosine-guanine (CpG) sites was correlated with better or worse overall survival (OS) in LIHC and GINS3 was also closely correlated with m6A modification. Moreover, results supported that GINS3 could influence the tumor microenvironment and relate to the immune checkpoints. CONCLUSIONS: Taken together, comprehensive analyses from this study supported GINS3 as a novel targeted biomarker in LIHC. |
format | Online Article Text |
id | pubmed-10248566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-102485662023-06-09 A novel prognostic biomarker: GINS3 is correlated with methylation and immune escape in liver hepatocellular carcinoma Lai, Tianqi Peng, Tianqi Li, Jinying Jiang, Yuchuan Liu, Kangshou Yu, Wei Yao, Nan Hu, Youzhu Cao, Mingrong Liang, Junjie Transl Cancer Res Original Article BACKGROUND: Liver cancer remains one of the tricky malignancies nowadays. GINS complex subunit 3 (GINS3), part of the GINS tetrameric complex, is significantly upregulated in many cancers, including liver hepatocellular carcinoma (LIHC). With the development of liver cancer treatment, immune and molecular targeted therapy gradually becomes a promising treatment. However, the key target for liver cancer is still indistinct. Herein, the underneath mechanism of GINS3 was investigated to verify its role as a biomarker in LIHC. METHODS: Genomic expression, genetic alteration, and methylation analyses were obtained from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), The University of Alabama at Birmingham CANcer (UALCN), and Human Protein Atlas (HPA), cBioPortal, and MethSurv databases. Subsequently, the diagnostic and prognostic role of GINS3 in LIHC were analyzed based on data from receiver operating characteristic (ROC), Kaplan-Meier plotter (KM-plotter), and univariate and multivariate cox regression analyses. The functional analyses were conducted with GeneMANIA and STRING databases, gene-gene, and protein-protein interaction (PPI) networks, Gene Ontology (GO) term, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Tumor Immune Estimation Resource (TIMER), Tumor-Immune System Interaction Database (TISIDB), and Gene Expression Profiling Interactive Analysis (GEPIA) were utilized to explore the internal connection with the immune escape. RESULTS: Through the analyses of genomic expression, GINS3 was significantly upregulated in LIHC and positively correlated with higher T classification. ROC analysis indicated GINS3 as a potential biomarker in the diagnosis of LIHC. KM-plotter, univariate and multivariate cox regression analyses both associated GINS3 with poor prognosis in LIHC patients. GINS3 genetic alteration, gene-gene interaction, PPI networks, and enrichment analysis further revealed that GINS3 played a pivotal role in the progression of LIHC. Furthermore, hypermethylation of GINS3 at different cytosine-guanine (CpG) sites was correlated with better or worse overall survival (OS) in LIHC and GINS3 was also closely correlated with m6A modification. Moreover, results supported that GINS3 could influence the tumor microenvironment and relate to the immune checkpoints. CONCLUSIONS: Taken together, comprehensive analyses from this study supported GINS3 as a novel targeted biomarker in LIHC. AME Publishing Company 2023-04-27 2023-05-31 /pmc/articles/PMC10248566/ /pubmed/37304536 http://dx.doi.org/10.21037/tcr-22-2565 Text en 2023 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Lai, Tianqi Peng, Tianqi Li, Jinying Jiang, Yuchuan Liu, Kangshou Yu, Wei Yao, Nan Hu, Youzhu Cao, Mingrong Liang, Junjie A novel prognostic biomarker: GINS3 is correlated with methylation and immune escape in liver hepatocellular carcinoma |
title | A novel prognostic biomarker: GINS3 is correlated with methylation and immune escape in liver hepatocellular carcinoma |
title_full | A novel prognostic biomarker: GINS3 is correlated with methylation and immune escape in liver hepatocellular carcinoma |
title_fullStr | A novel prognostic biomarker: GINS3 is correlated with methylation and immune escape in liver hepatocellular carcinoma |
title_full_unstemmed | A novel prognostic biomarker: GINS3 is correlated with methylation and immune escape in liver hepatocellular carcinoma |
title_short | A novel prognostic biomarker: GINS3 is correlated with methylation and immune escape in liver hepatocellular carcinoma |
title_sort | novel prognostic biomarker: gins3 is correlated with methylation and immune escape in liver hepatocellular carcinoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10248566/ https://www.ncbi.nlm.nih.gov/pubmed/37304536 http://dx.doi.org/10.21037/tcr-22-2565 |
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