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Characterization of prognostic value and immunological roles of RAB22A in hepatocellular carcinoma

BACKGROUND: The protein-coding gene RAB22A, a member of the RAS oncogene family, is amplified or overexpressed in certain cancers. However, its action mechanism in hepatocellular carcinoma (HCC) remains unclear. Here, we aimed to examine the connection between RAB22A and survival prognosis in HCC an...

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Autores principales: Wen, Fukai, Meng, Fanshuai, Li, Xuewen, Li, Qingyu, Liu, Jiaming, Zhang, Rui, Zhao, Yunzheng, Zhang, Yu, Wang, Xin, Ju, Shuai, Cui, Yifeng, Lu, Zhaoyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10021109/
https://www.ncbi.nlm.nih.gov/pubmed/36936971
http://dx.doi.org/10.3389/fimmu.2023.1086342
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author Wen, Fukai
Meng, Fanshuai
Li, Xuewen
Li, Qingyu
Liu, Jiaming
Zhang, Rui
Zhao, Yunzheng
Zhang, Yu
Wang, Xin
Ju, Shuai
Cui, Yifeng
Lu, Zhaoyang
author_facet Wen, Fukai
Meng, Fanshuai
Li, Xuewen
Li, Qingyu
Liu, Jiaming
Zhang, Rui
Zhao, Yunzheng
Zhang, Yu
Wang, Xin
Ju, Shuai
Cui, Yifeng
Lu, Zhaoyang
author_sort Wen, Fukai
collection PubMed
description BACKGROUND: The protein-coding gene RAB22A, a member of the RAS oncogene family, is amplified or overexpressed in certain cancers. However, its action mechanism in hepatocellular carcinoma (HCC) remains unclear. Here, we aimed to examine the connection between RAB22A and survival prognosis in HCC and explore the biological significance of RAB22A. METHODS: A database-based pan-cancer expression analysis of RAB22A was performed. Kaplan–Meier analysis and Cox regression were performed to evaluate the association between RAB22A expression and survival prognosis in HCC. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), various potential biological functions and regulatory pathways of RAB22A in HCC were discovered. Tumor immune infiltration was studied using the single sample gene set enrichment analysis (ssGSEA) method. N6-methyladenosine modifications and the regulatory network of competitive endogenous RNA (ceRNA) were verified in the TCGA cohort. RESULTS: RAB22A was upregulated in HCC samples and cell lines. A high RAB22A expression in HCC was strongly correlated with sex, race, age, weight, TNM stage, pathological stage, tumor status, histologic grade, TP53 mutation status, and alpha fetal protein (AFP) levels. Overexpression of RAB22A indicated a poor prognosis was related to overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). GO and KEGG analyses revealed that the differentially expressed genes related to RAB22A might be involved in the proteasomal protein catabolic process, ncRNA processing, ribosome ribosomal subunit, protein serine/threonine kinase activity, protein serine kinase activity, Endocytosis, and non-alcoholic fatty liver disease. GSEA analyses revealed that the differentially expressed genes related to RAB22A might be involved in the T cell receptor, a co-translational protein, that binds to the membrane, axon guidance, ribosome, phagocytosis, and Eukaryotic translation initiation. RAB22A was correlated with N6-methyladenosine expression in HCC and established RAB22A-related ceRNA regulatory networks. Finally,RAB22A expression was positively connected the levels of infiltrating with T helper cells, Tcm cells, and Th2 cells,In contrast, we observed negatively correlations with cytotoxic cells, DCs, and pDCs cells.Moreover,RAB22A expression showed a strong correlation with various immunomarkergroups in HCC. CONCLUSIONS: RAB22A is a potential therapeutic target for improving HCC prognosis and is closely related to immune cell infiltration.
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spelling pubmed-100211092023-03-18 Characterization of prognostic value and immunological roles of RAB22A in hepatocellular carcinoma Wen, Fukai Meng, Fanshuai Li, Xuewen Li, Qingyu Liu, Jiaming Zhang, Rui Zhao, Yunzheng Zhang, Yu Wang, Xin Ju, Shuai Cui, Yifeng Lu, Zhaoyang Front Immunol Immunology BACKGROUND: The protein-coding gene RAB22A, a member of the RAS oncogene family, is amplified or overexpressed in certain cancers. However, its action mechanism in hepatocellular carcinoma (HCC) remains unclear. Here, we aimed to examine the connection between RAB22A and survival prognosis in HCC and explore the biological significance of RAB22A. METHODS: A database-based pan-cancer expression analysis of RAB22A was performed. Kaplan–Meier analysis and Cox regression were performed to evaluate the association between RAB22A expression and survival prognosis in HCC. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), various potential biological functions and regulatory pathways of RAB22A in HCC were discovered. Tumor immune infiltration was studied using the single sample gene set enrichment analysis (ssGSEA) method. N6-methyladenosine modifications and the regulatory network of competitive endogenous RNA (ceRNA) were verified in the TCGA cohort. RESULTS: RAB22A was upregulated in HCC samples and cell lines. A high RAB22A expression in HCC was strongly correlated with sex, race, age, weight, TNM stage, pathological stage, tumor status, histologic grade, TP53 mutation status, and alpha fetal protein (AFP) levels. Overexpression of RAB22A indicated a poor prognosis was related to overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). GO and KEGG analyses revealed that the differentially expressed genes related to RAB22A might be involved in the proteasomal protein catabolic process, ncRNA processing, ribosome ribosomal subunit, protein serine/threonine kinase activity, protein serine kinase activity, Endocytosis, and non-alcoholic fatty liver disease. GSEA analyses revealed that the differentially expressed genes related to RAB22A might be involved in the T cell receptor, a co-translational protein, that binds to the membrane, axon guidance, ribosome, phagocytosis, and Eukaryotic translation initiation. RAB22A was correlated with N6-methyladenosine expression in HCC and established RAB22A-related ceRNA regulatory networks. Finally,RAB22A expression was positively connected the levels of infiltrating with T helper cells, Tcm cells, and Th2 cells,In contrast, we observed negatively correlations with cytotoxic cells, DCs, and pDCs cells.Moreover,RAB22A expression showed a strong correlation with various immunomarkergroups in HCC. CONCLUSIONS: RAB22A is a potential therapeutic target for improving HCC prognosis and is closely related to immune cell infiltration. Frontiers Media S.A. 2023-03-03 /pmc/articles/PMC10021109/ /pubmed/36936971 http://dx.doi.org/10.3389/fimmu.2023.1086342 Text en Copyright © 2023 Wen, Meng, Li, Li, Liu, Zhang, Zhao, Zhang, Wang, Ju, Cui and Lu 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
Wen, Fukai
Meng, Fanshuai
Li, Xuewen
Li, Qingyu
Liu, Jiaming
Zhang, Rui
Zhao, Yunzheng
Zhang, Yu
Wang, Xin
Ju, Shuai
Cui, Yifeng
Lu, Zhaoyang
Characterization of prognostic value and immunological roles of RAB22A in hepatocellular carcinoma
title Characterization of prognostic value and immunological roles of RAB22A in hepatocellular carcinoma
title_full Characterization of prognostic value and immunological roles of RAB22A in hepatocellular carcinoma
title_fullStr Characterization of prognostic value and immunological roles of RAB22A in hepatocellular carcinoma
title_full_unstemmed Characterization of prognostic value and immunological roles of RAB22A in hepatocellular carcinoma
title_short Characterization of prognostic value and immunological roles of RAB22A in hepatocellular carcinoma
title_sort characterization of prognostic value and immunological roles of rab22a in hepatocellular carcinoma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10021109/
https://www.ncbi.nlm.nih.gov/pubmed/36936971
http://dx.doi.org/10.3389/fimmu.2023.1086342
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