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Low expression of AQP9 and its value in hepatocellular carcinoma

BACKGROUND: The mortality rate for liver cancer is high worldwide. The etiology of liver cancer has altered with the high incidence rate of non-alcoholic fatty liver disease (NAFLD) although effective vaccination strategies have been developed. Therefore, it is important to discover new biomarkers f...

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Autores principales: Gao, Cheng, Shen, Jianbo, Yao, Lanqing, Xia, Zhenguo, Liang, Xiaoliang, Zhu, Renfei, Chen, Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798023/
https://www.ncbi.nlm.nih.gov/pubmed/35116505
http://dx.doi.org/10.21037/tcr-20-3158
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author Gao, Cheng
Shen, Jianbo
Yao, Lanqing
Xia, Zhenguo
Liang, Xiaoliang
Zhu, Renfei
Chen, Zhong
author_facet Gao, Cheng
Shen, Jianbo
Yao, Lanqing
Xia, Zhenguo
Liang, Xiaoliang
Zhu, Renfei
Chen, Zhong
author_sort Gao, Cheng
collection PubMed
description BACKGROUND: The mortality rate for liver cancer is high worldwide. The etiology of liver cancer has altered with the high incidence rate of non-alcoholic fatty liver disease (NAFLD) although effective vaccination strategies have been developed. Therefore, it is important to discover new biomarkers for diagnosis and prognosis. Aquaporin 9 (AQP9) has been reported in some cancers, especially in liver cancer, although its role in this malignancy remains to be clarified. In this study, we conducted a bioinformatics analysis to clarify the function of AQP9 in liver cancer. METHODS: Immunohistochemistry, real-time qPCR, western blot analysis were applied to detect AQP9 expression in tissue samples or cells. Online databases were used to analyze the correlation of AQP9 expression and clinical factors. LinkedOmics and gene set enrichment analysis (GSEA) were used to analyze the functional network of AQP9 in hepatocellular carcinoma (HCC). Four authoritative databases were used to predict the candidate microRNAs that bind to AQP9. Finally, we used the Tumor Immune Estimation Resource (TIMER) to assess the correlation of AQP9 and immune cell infiltration in HCC. RESULTS: All analysis were revealed AQP9 is significantly decreased in HCC tissues and cells. AQP9 was negatively correlated with different tumor stage, grade, and weight, as well as lymph node metastasis, sex, and histological subtypes. AQP9 can be used to predict the prognosis of HCC patients. GSEA revealed that AQP9 was significantly involved in most significant hallmark pathways. LinkedOmics was used to analyze the relationship of AQP9 with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Mechanistically, mir-23a-3p and mir-330-3p may downregulate AQP9 expression in HCC. AQP9 was found to be specifically correlated with immune cell infiltration and play a major role in the liver cancer microenvironment. CONCLUSIONS: In this study, we found that AQP9 was significantly decreased in HCC, with low AQP9 levels indicating a poor outcome. GSEA analysis and LinkedOmics revealed that AQP9 was significantly involved in the most significant hallmarks pathways. Mir-23a-3p and mir-330-3p may inhibit AQP9 expression in HCC. Our results also suggest that AQP9 is important in tumor immunity in the liver cancer.
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spelling pubmed-87980232022-02-02 Low expression of AQP9 and its value in hepatocellular carcinoma Gao, Cheng Shen, Jianbo Yao, Lanqing Xia, Zhenguo Liang, Xiaoliang Zhu, Renfei Chen, Zhong Transl Cancer Res Original Article BACKGROUND: The mortality rate for liver cancer is high worldwide. The etiology of liver cancer has altered with the high incidence rate of non-alcoholic fatty liver disease (NAFLD) although effective vaccination strategies have been developed. Therefore, it is important to discover new biomarkers for diagnosis and prognosis. Aquaporin 9 (AQP9) has been reported in some cancers, especially in liver cancer, although its role in this malignancy remains to be clarified. In this study, we conducted a bioinformatics analysis to clarify the function of AQP9 in liver cancer. METHODS: Immunohistochemistry, real-time qPCR, western blot analysis were applied to detect AQP9 expression in tissue samples or cells. Online databases were used to analyze the correlation of AQP9 expression and clinical factors. LinkedOmics and gene set enrichment analysis (GSEA) were used to analyze the functional network of AQP9 in hepatocellular carcinoma (HCC). Four authoritative databases were used to predict the candidate microRNAs that bind to AQP9. Finally, we used the Tumor Immune Estimation Resource (TIMER) to assess the correlation of AQP9 and immune cell infiltration in HCC. RESULTS: All analysis were revealed AQP9 is significantly decreased in HCC tissues and cells. AQP9 was negatively correlated with different tumor stage, grade, and weight, as well as lymph node metastasis, sex, and histological subtypes. AQP9 can be used to predict the prognosis of HCC patients. GSEA revealed that AQP9 was significantly involved in most significant hallmark pathways. LinkedOmics was used to analyze the relationship of AQP9 with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Mechanistically, mir-23a-3p and mir-330-3p may downregulate AQP9 expression in HCC. AQP9 was found to be specifically correlated with immune cell infiltration and play a major role in the liver cancer microenvironment. CONCLUSIONS: In this study, we found that AQP9 was significantly decreased in HCC, with low AQP9 levels indicating a poor outcome. GSEA analysis and LinkedOmics revealed that AQP9 was significantly involved in the most significant hallmarks pathways. Mir-23a-3p and mir-330-3p may inhibit AQP9 expression in HCC. Our results also suggest that AQP9 is important in tumor immunity in the liver cancer. AME Publishing Company 2021-04 /pmc/articles/PMC8798023/ /pubmed/35116505 http://dx.doi.org/10.21037/tcr-20-3158 Text en 2021 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/.
spellingShingle Original Article
Gao, Cheng
Shen, Jianbo
Yao, Lanqing
Xia, Zhenguo
Liang, Xiaoliang
Zhu, Renfei
Chen, Zhong
Low expression of AQP9 and its value in hepatocellular carcinoma
title Low expression of AQP9 and its value in hepatocellular carcinoma
title_full Low expression of AQP9 and its value in hepatocellular carcinoma
title_fullStr Low expression of AQP9 and its value in hepatocellular carcinoma
title_full_unstemmed Low expression of AQP9 and its value in hepatocellular carcinoma
title_short Low expression of AQP9 and its value in hepatocellular carcinoma
title_sort low expression of aqp9 and its value in hepatocellular carcinoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798023/
https://www.ncbi.nlm.nih.gov/pubmed/35116505
http://dx.doi.org/10.21037/tcr-20-3158
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