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Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma

Dysregulation and prognostic roles of Karyopherin α2 (KPNA2) were reported in many malignancies including hepatocellular carcinoma (HCC). A multi-omics analysis of KPNA2 is needed to gain a deeper understanding of its multilevel molecular characteristics and provide novel clues for HCC diagnosis, pr...

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Autores principales: Zhang, Jinzhong, Zhang, Xiuzhi, Wang, Lingxiao, Kang, Chunyan, Li, Ningning, Xiao, Zhefeng, Dai, Liping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462373/
https://www.ncbi.nlm.nih.gov/pubmed/34616632
http://dx.doi.org/10.7717/peerj.12197
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author Zhang, Jinzhong
Zhang, Xiuzhi
Wang, Lingxiao
Kang, Chunyan
Li, Ningning
Xiao, Zhefeng
Dai, Liping
author_facet Zhang, Jinzhong
Zhang, Xiuzhi
Wang, Lingxiao
Kang, Chunyan
Li, Ningning
Xiao, Zhefeng
Dai, Liping
author_sort Zhang, Jinzhong
collection PubMed
description Dysregulation and prognostic roles of Karyopherin α2 (KPNA2) were reported in many malignancies including hepatocellular carcinoma (HCC). A multi-omics analysis of KPNA2 is needed to gain a deeper understanding of its multilevel molecular characteristics and provide novel clues for HCC diagnosis, prognosis, and target therapy. Herein multi-omic alterations of KPNA2 were analyzed at genetic, epigenetic, transcript, and protein levels with evaluation of their relevance with clinicopathological features of HCC by integrative analyses. The significant correlations of KPNA2 expression with its gene copy number variation (CNV) and methylation status were shown through Spearman correlation analyses. With Cox regression, Kaplan-Meier survival, and receiver operating characteristic (ROC) analyses, based on the factors of KPNA2 CNV, methylation, expression, and tumor stage, risk models for HCC overall survival (OS) and disease-free survival (DFS) were constructed which could discriminate the 1-year, 3-year, and 5-year OS/DFS status effectively. With Microenvironment Cell Populations-counter (MCP-counter), the immune infiltrations of HCC samples were evaluated and their associations with KPNA2 were shown. KPNA2 expression in liver was found to be influenced by low fat diet and presented significant correlations with fatty acid metabolism and fatty acid synthase activity in HCC. KPNA2 was detected lowered in HCC patient’s plasma by enzyme linked immunosorbent assay (ELISA), consistent with its translocation to nuclei of HCC cells. In conclusion, KPNA2 multilevel dysregulation in HCC and its correlations with immune infiltration and the fatty acid metabolism pathway indicated its multiple roles in HCC. The clinicopathological significance of KPNA2 was highlighted through the in-depth analyses at multilevels.
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spelling pubmed-84623732021-10-05 Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma Zhang, Jinzhong Zhang, Xiuzhi Wang, Lingxiao Kang, Chunyan Li, Ningning Xiao, Zhefeng Dai, Liping PeerJ Bioinformatics Dysregulation and prognostic roles of Karyopherin α2 (KPNA2) were reported in many malignancies including hepatocellular carcinoma (HCC). A multi-omics analysis of KPNA2 is needed to gain a deeper understanding of its multilevel molecular characteristics and provide novel clues for HCC diagnosis, prognosis, and target therapy. Herein multi-omic alterations of KPNA2 were analyzed at genetic, epigenetic, transcript, and protein levels with evaluation of their relevance with clinicopathological features of HCC by integrative analyses. The significant correlations of KPNA2 expression with its gene copy number variation (CNV) and methylation status were shown through Spearman correlation analyses. With Cox regression, Kaplan-Meier survival, and receiver operating characteristic (ROC) analyses, based on the factors of KPNA2 CNV, methylation, expression, and tumor stage, risk models for HCC overall survival (OS) and disease-free survival (DFS) were constructed which could discriminate the 1-year, 3-year, and 5-year OS/DFS status effectively. With Microenvironment Cell Populations-counter (MCP-counter), the immune infiltrations of HCC samples were evaluated and their associations with KPNA2 were shown. KPNA2 expression in liver was found to be influenced by low fat diet and presented significant correlations with fatty acid metabolism and fatty acid synthase activity in HCC. KPNA2 was detected lowered in HCC patient’s plasma by enzyme linked immunosorbent assay (ELISA), consistent with its translocation to nuclei of HCC cells. In conclusion, KPNA2 multilevel dysregulation in HCC and its correlations with immune infiltration and the fatty acid metabolism pathway indicated its multiple roles in HCC. The clinicopathological significance of KPNA2 was highlighted through the in-depth analyses at multilevels. PeerJ Inc. 2021-09-21 /pmc/articles/PMC8462373/ /pubmed/34616632 http://dx.doi.org/10.7717/peerj.12197 Text en ©2021 Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Bioinformatics
Zhang, Jinzhong
Zhang, Xiuzhi
Wang, Lingxiao
Kang, Chunyan
Li, Ningning
Xiao, Zhefeng
Dai, Liping
Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma
title Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma
title_full Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma
title_fullStr Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma
title_full_unstemmed Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma
title_short Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma
title_sort multiomics-based analyses of kpna2 highlight its multiple potentials in hepatocellular carcinoma
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462373/
https://www.ncbi.nlm.nih.gov/pubmed/34616632
http://dx.doi.org/10.7717/peerj.12197
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