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Comprehensive Analysis of SLC17A9 and Its Prognostic Value in Hepatocellular Carcinoma

BACKGROUND: Solute carrier family 17 member 9 (SLC17A9) encodes a member of a family of transmembrane proteins that are involved in the transport of small molecules. SLC17A9 is involved in the occurrence and development of various cancers, but its biological role in liver hepatocellular carcinoma (L...

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Autores principales: Kui, Xue-Yan, Gao, Yan, Liu, Xu-Sheng, Zeng, Jing, Yang, Jian-Wei, Zhou, Lu-Meng, Liu, Xiao-Yu, Zhang, Yu, Zhang, Yao-Hua, Pei, Zhi-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357942/
https://www.ncbi.nlm.nih.gov/pubmed/35957868
http://dx.doi.org/10.3389/fonc.2022.809847
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author Kui, Xue-Yan
Gao, Yan
Liu, Xu-Sheng
Zeng, Jing
Yang, Jian-Wei
Zhou, Lu-Meng
Liu, Xiao-Yu
Zhang, Yu
Zhang, Yao-Hua
Pei, Zhi-Jun
author_facet Kui, Xue-Yan
Gao, Yan
Liu, Xu-Sheng
Zeng, Jing
Yang, Jian-Wei
Zhou, Lu-Meng
Liu, Xiao-Yu
Zhang, Yu
Zhang, Yao-Hua
Pei, Zhi-Jun
author_sort Kui, Xue-Yan
collection PubMed
description BACKGROUND: Solute carrier family 17 member 9 (SLC17A9) encodes a member of a family of transmembrane proteins that are involved in the transport of small molecules. SLC17A9 is involved in the occurrence and development of various cancers, but its biological role in liver hepatocellular carcinoma (LIHC) is unclear. METHODS: The expression level of SLC17A9 was assessed using The Cancer Genome Atlas (TCGA) database and immunohistochemistry of tumor tissues and adjacent normal liver tissues. The receiver operating characteristic (ROC) and R software package performed diagnosis and prognosis. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes functional enrichment and co-expression of SLC17A9, gene–gene interaction (GGI), and protein–protein interaction (PPI) networks were performed using R, GeneMANIA, and STRING. Western blot, real-time quantitative PCR (RT-qPCR), immunofluorescence, colony formation, wound scratch assay, ATP production assays, and high connotation were applied to determine the effect of SLC17A9 knockdown on HEPG2 (hepatocellular liver carcinoma) cells. TIMER, GEPIA, and TCGA analyzed the relationship between SLC17A9 expression and immune cells, m6A modification, and ferroptosis. RESULTS: SLC17A9 expression in LIHC tissues was higher than in normal liver tissues (p < 0.001), and SLC17A9 was related to sex, DSS (disease-specific survival), and PFI (progression-free interval) (p = 0.015, 0.006, and 0.023). SLC17A9 expression has diagnostic (AUC: 0.812; CI: 0.770–0.854) and prognostic potential (p = 0.015) in LIHC. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) functional enrichment analysis showed that SLC17A9 was closely related to neuronal cell body, presynapse, axonogenesis, PI3K/Akt signaling pathway. GGI showed that SLC17A9 was closely related to MYO5A. PPI showed that SLC17A9 was closely related to SLC18A3. SLC17A9 silencing inhibited HepG2 cells proliferation, migration, colony formation, and reduced their ATP level. SLC17A9 expression level was related to immune cells: B cells (r = 0.094, P = 8.06E-02), CD4(+) T cells (r = 0.184, P = 5.95E-04), and macrophages (r = 0.137, P = 1.15E-02); m6A modification: HNRNPC (r = 0.220, p < 0.001), METTL3 (r = 0.180, p < 0.001), and WTAP (r = 0.130, p = 0.009); and ferroptosis: HSPA5 (r = 0.240, p < 0.001), SLC7A11 (r = 0.180, p < 0.001), and FANCD2 (r = 0.280, p < 0.001). CONCLUSION: Our data show that SLC17A9 may influence LIHC progression. SLC17A9 expression correlates with tumor immune infiltration, m6A modification, and ferroptosis in LIHC and may have diagnostic and prognostic value in LIHC.
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spelling pubmed-93579422022-08-10 Comprehensive Analysis of SLC17A9 and Its Prognostic Value in Hepatocellular Carcinoma Kui, Xue-Yan Gao, Yan Liu, Xu-Sheng Zeng, Jing Yang, Jian-Wei Zhou, Lu-Meng Liu, Xiao-Yu Zhang, Yu Zhang, Yao-Hua Pei, Zhi-Jun Front Oncol Oncology BACKGROUND: Solute carrier family 17 member 9 (SLC17A9) encodes a member of a family of transmembrane proteins that are involved in the transport of small molecules. SLC17A9 is involved in the occurrence and development of various cancers, but its biological role in liver hepatocellular carcinoma (LIHC) is unclear. METHODS: The expression level of SLC17A9 was assessed using The Cancer Genome Atlas (TCGA) database and immunohistochemistry of tumor tissues and adjacent normal liver tissues. The receiver operating characteristic (ROC) and R software package performed diagnosis and prognosis. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes functional enrichment and co-expression of SLC17A9, gene–gene interaction (GGI), and protein–protein interaction (PPI) networks were performed using R, GeneMANIA, and STRING. Western blot, real-time quantitative PCR (RT-qPCR), immunofluorescence, colony formation, wound scratch assay, ATP production assays, and high connotation were applied to determine the effect of SLC17A9 knockdown on HEPG2 (hepatocellular liver carcinoma) cells. TIMER, GEPIA, and TCGA analyzed the relationship between SLC17A9 expression and immune cells, m6A modification, and ferroptosis. RESULTS: SLC17A9 expression in LIHC tissues was higher than in normal liver tissues (p < 0.001), and SLC17A9 was related to sex, DSS (disease-specific survival), and PFI (progression-free interval) (p = 0.015, 0.006, and 0.023). SLC17A9 expression has diagnostic (AUC: 0.812; CI: 0.770–0.854) and prognostic potential (p = 0.015) in LIHC. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) functional enrichment analysis showed that SLC17A9 was closely related to neuronal cell body, presynapse, axonogenesis, PI3K/Akt signaling pathway. GGI showed that SLC17A9 was closely related to MYO5A. PPI showed that SLC17A9 was closely related to SLC18A3. SLC17A9 silencing inhibited HepG2 cells proliferation, migration, colony formation, and reduced their ATP level. SLC17A9 expression level was related to immune cells: B cells (r = 0.094, P = 8.06E-02), CD4(+) T cells (r = 0.184, P = 5.95E-04), and macrophages (r = 0.137, P = 1.15E-02); m6A modification: HNRNPC (r = 0.220, p < 0.001), METTL3 (r = 0.180, p < 0.001), and WTAP (r = 0.130, p = 0.009); and ferroptosis: HSPA5 (r = 0.240, p < 0.001), SLC7A11 (r = 0.180, p < 0.001), and FANCD2 (r = 0.280, p < 0.001). CONCLUSION: Our data show that SLC17A9 may influence LIHC progression. SLC17A9 expression correlates with tumor immune infiltration, m6A modification, and ferroptosis in LIHC and may have diagnostic and prognostic value in LIHC. Frontiers Media S.A. 2022-07-25 /pmc/articles/PMC9357942/ /pubmed/35957868 http://dx.doi.org/10.3389/fonc.2022.809847 Text en Copyright © 2022 Kui, Gao, Liu, Zeng, Yang, Zhou, Liu, Zhang, Zhang and Pei 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 Oncology
Kui, Xue-Yan
Gao, Yan
Liu, Xu-Sheng
Zeng, Jing
Yang, Jian-Wei
Zhou, Lu-Meng
Liu, Xiao-Yu
Zhang, Yu
Zhang, Yao-Hua
Pei, Zhi-Jun
Comprehensive Analysis of SLC17A9 and Its Prognostic Value in Hepatocellular Carcinoma
title Comprehensive Analysis of SLC17A9 and Its Prognostic Value in Hepatocellular Carcinoma
title_full Comprehensive Analysis of SLC17A9 and Its Prognostic Value in Hepatocellular Carcinoma
title_fullStr Comprehensive Analysis of SLC17A9 and Its Prognostic Value in Hepatocellular Carcinoma
title_full_unstemmed Comprehensive Analysis of SLC17A9 and Its Prognostic Value in Hepatocellular Carcinoma
title_short Comprehensive Analysis of SLC17A9 and Its Prognostic Value in Hepatocellular Carcinoma
title_sort comprehensive analysis of slc17a9 and its prognostic value in hepatocellular carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357942/
https://www.ncbi.nlm.nih.gov/pubmed/35957868
http://dx.doi.org/10.3389/fonc.2022.809847
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