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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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2023/8456833 |
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| author | Xixi Xiang Fu Li Sha Zhou Yunjing Zeng Xiaojuan Deng Hongyang Zhang Jiali Li Hongyun Liu Jun Rao Lei Gao Cheng Zhang Qin Wen Li Gao Xi Zhang |
| author_facet | Xixi Xiang Fu Li Sha Zhou Yunjing Zeng Xiaojuan Deng Hongyang Zhang Jiali Li Hongyun Liu Jun Rao Lei Gao Cheng Zhang Qin Wen Li Gao Xi Zhang |
| author_sort | Xixi Xiang |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-fd80b6d8f721452f9082b0c58d1789dd |
| institution | OA Journals |
| issn | 1687-4765 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-fd80b6d8f721452f9082b0c58d1789dd2025-08-20T02:22:39ZengWileyPPAR Research1687-47652023-01-01202310.1155/2023/8456833Significance of PPARA as a Treatment Target for Chronic Lymphocytic LeukemiaXixi Xiang0Fu Li1Sha Zhou2Yunjing Zeng3Xiaojuan Deng4Hongyang Zhang5Jiali Li6Hongyun Liu7Jun Rao8Lei Gao9Cheng Zhang10Qin Wen11Li Gao12Xi Zhang13State Key Laboratory of TraumaState Key Laboratory of TraumaState Key Laboratory of TraumaState Key Laboratory of TraumaState Key Laboratory of TraumaState Key Laboratory of TraumaState Key Laboratory of TraumaState Key Laboratory of TraumaState Key Laboratory of TraumaState Key Laboratory of TraumaState Key Laboratory of TraumaState Key Laboratory of TraumaState Key Laboratory of TraumaState Key Laboratory of TraumaPeroxisome 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.http://dx.doi.org/10.1155/2023/8456833 |
| spellingShingle | Xixi Xiang Fu Li Sha Zhou Yunjing Zeng Xiaojuan Deng Hongyang Zhang Jiali Li Hongyun Liu Jun Rao Lei Gao Cheng Zhang Qin Wen Li Gao Xi Zhang Significance of PPARA as a Treatment Target for Chronic Lymphocytic Leukemia PPAR Research |
| 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 |
| url | http://dx.doi.org/10.1155/2023/8456833 |
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