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Significance of PPARA as a Treatment Target for Chronic Lymphocytic Leukemia

Peroxisome proliferator-activated receptor alpha (PPARA) has been suggested as a therapeutic target for chronic lymphocytic leukemia (CLL). However, the underlying molecular mechanism remains largely unclear. In this study, we analyzed DNA next-generation sequencing (NGS) data and clinical informati...

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Autores principales: Xiang, Xixi, Li, Fu, Zhou, Sha, Zeng, Yunjing, Deng, Xiaojuan, Zhang, Hongyang, Li, Jiali, Liu, Hongyun, Rao, Jun, Gao, Lei, Zhang, Cheng, Wen, Qin, Gao, Li, Zhang, Xi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317583/
https://www.ncbi.nlm.nih.gov/pubmed/37404899
http://dx.doi.org/10.1155/2023/8456833
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author Xiang, Xixi
Li, Fu
Zhou, Sha
Zeng, Yunjing
Deng, Xiaojuan
Zhang, Hongyang
Li, Jiali
Liu, Hongyun
Rao, Jun
Gao, Lei
Zhang, Cheng
Wen, Qin
Gao, Li
Zhang, Xi
author_facet Xiang, Xixi
Li, Fu
Zhou, Sha
Zeng, Yunjing
Deng, Xiaojuan
Zhang, Hongyang
Li, Jiali
Liu, Hongyun
Rao, Jun
Gao, Lei
Zhang, Cheng
Wen, Qin
Gao, Li
Zhang, Xi
author_sort Xiang, Xixi
collection PubMed
description Peroxisome proliferator-activated receptor alpha (PPARA) has been suggested as a therapeutic target for chronic lymphocytic leukemia (CLL). However, the underlying molecular mechanism remains largely unclear. In this study, we analyzed DNA next-generation sequencing (NGS) data and clinical information from 86 CLL patients to identify gene markers related to treatment-free survival (TFS) length. We then constructed a genetic network that includes CLL promoters, treatment targets, and TFS-related marker genes. To assess the significance of PPARA within the network, we utilized degree centrality (DC) and pathway enrichment score (EScore). Clinical and NGS data revealed 10 TFS length-related gene markers, including RPS15, FOXO1, FBXW7, KMT2A, NOTCH1, GNA12, EGR2, GNA13, KDM6A, and ATM. Through literature data mining, 83 genes were identified as CLL upstream promoters and treatment targets. Among them, PPARA exhibited a stronger connection to CLL and TFS-related gene markers, as evidenced by its ranking at No. 13 based on DC, compared to most of the other promoters (>84%). Additionally, PPARA co-functions with 70 out of 92 in-network genes in various functional pathways/gene groups related to CLL pathology, such as regulation of cell adhesion, inflammation, reactive oxygen species, and cell differentiation. Based on our findings, PPARA is considered one of the critical genes within a large genetic network that influences the prognosis and TFS of CLL through multiple pathogenic pathways.
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spelling pubmed-103175832023-07-04 Significance of PPARA as a Treatment Target for Chronic Lymphocytic Leukemia Xiang, Xixi Li, Fu Zhou, Sha Zeng, Yunjing Deng, Xiaojuan Zhang, Hongyang Li, Jiali Liu, Hongyun Rao, Jun Gao, Lei Zhang, Cheng Wen, Qin Gao, Li Zhang, Xi PPAR Res Research Article Peroxisome proliferator-activated receptor alpha (PPARA) has been suggested as a therapeutic target for chronic lymphocytic leukemia (CLL). However, the underlying molecular mechanism remains largely unclear. In this study, we analyzed DNA next-generation sequencing (NGS) data and clinical information from 86 CLL patients to identify gene markers related to treatment-free survival (TFS) length. We then constructed a genetic network that includes CLL promoters, treatment targets, and TFS-related marker genes. To assess the significance of PPARA within the network, we utilized degree centrality (DC) and pathway enrichment score (EScore). Clinical and NGS data revealed 10 TFS length-related gene markers, including RPS15, FOXO1, FBXW7, KMT2A, NOTCH1, GNA12, EGR2, GNA13, KDM6A, and ATM. Through literature data mining, 83 genes were identified as CLL upstream promoters and treatment targets. Among them, PPARA exhibited a stronger connection to CLL and TFS-related gene markers, as evidenced by its ranking at No. 13 based on DC, compared to most of the other promoters (>84%). Additionally, PPARA co-functions with 70 out of 92 in-network genes in various functional pathways/gene groups related to CLL pathology, such as regulation of cell adhesion, inflammation, reactive oxygen species, and cell differentiation. Based on our findings, PPARA is considered one of the critical genes within a large genetic network that influences the prognosis and TFS of CLL through multiple pathogenic pathways. Hindawi 2023-06-26 /pmc/articles/PMC10317583/ /pubmed/37404899 http://dx.doi.org/10.1155/2023/8456833 Text en Copyright © 2023 Xixi Xiang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Xiang, Xixi
Li, Fu
Zhou, Sha
Zeng, Yunjing
Deng, Xiaojuan
Zhang, Hongyang
Li, Jiali
Liu, Hongyun
Rao, Jun
Gao, Lei
Zhang, Cheng
Wen, Qin
Gao, Li
Zhang, Xi
Significance of PPARA as a Treatment Target for Chronic Lymphocytic Leukemia
title Significance of PPARA as a Treatment Target for Chronic Lymphocytic Leukemia
title_full Significance of PPARA as a Treatment Target for Chronic Lymphocytic Leukemia
title_fullStr Significance of PPARA as a Treatment Target for Chronic Lymphocytic Leukemia
title_full_unstemmed Significance of PPARA as a Treatment Target for Chronic Lymphocytic Leukemia
title_short Significance of PPARA as a Treatment Target for Chronic Lymphocytic Leukemia
title_sort significance of ppara as a treatment target for chronic lymphocytic leukemia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317583/
https://www.ncbi.nlm.nih.gov/pubmed/37404899
http://dx.doi.org/10.1155/2023/8456833
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