{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T21:51:12Z","timestamp":1773784272994,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chongqing Science and Health Joint Medical Youth Project","award":["2019QNXM021"],"award-info":[{"award-number":["2019QNXM021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["PPAR Research"],"published-print":{"date-parts":[[2023,6,26]]},"abstract":"<jats:p>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 (&gt;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.<\/jats:p>","DOI":"10.1155\/2023\/8456833","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:05:07Z","timestamp":1687824307000},"page":"1-11","source":"Crossref","is-referenced-by-count":3,"title":["Significance of PPARA as a Treatment Target for Chronic Lymphocytic Leukemia"],"prefix":"10.1155","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0610-5364","authenticated-orcid":true,"given":"Xixi","family":"Xiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6198-0682","authenticated-orcid":true,"given":"Fu","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-3721","authenticated-orcid":true,"given":"Sha","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9875-6967","authenticated-orcid":true,"given":"Yunjing","family":"Zeng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5304-0061","authenticated-orcid":true,"given":"Xiaojuan","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5959-6390","authenticated-orcid":true,"given":"Hongyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6297-4607","authenticated-orcid":true,"given":"Jiali","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4249-9520","authenticated-orcid":true,"given":"Hongyun","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3344-2932","authenticated-orcid":true,"given":"Jun","family":"Rao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2336-976X","authenticated-orcid":true,"given":"Lei","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0142-3307","authenticated-orcid":true,"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9494-3901","authenticated-orcid":true,"given":"Qin","family":"Wen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7458-385X","authenticated-orcid":true,"given":"Li","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8548-2832","authenticated-orcid":true,"given":"Xi","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury, Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Key Subject of Chongqing, Chongqing 400037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"issue":"2","key":"1","first-page":"605","article-title":"Chronic lymphocytic leukaemia","volume":"29","author":"J. Boelens","year":"2009","journal-title":"Anticancer Research"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-022-00423-y"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26367"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.1946"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.20036"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01054-w"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)10364-1"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.6.2160"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-3216-3"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.09.027"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.329"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2015.00139"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.061721"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2020.06.004"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2008.11.011"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4918"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2005.12.012"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.220"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1177\/0300060518783072"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-09-806398"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2018.3845"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-03-489468"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.02.064"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24176"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.267914"},{"key":"26","doi-asserted-by":"crossref","first-page":"101194","DOI":"10.1016\/j.plipres.2022.101194","article-title":"Anandamide and other N-acylethanolamines: a class of signaling lipids with therapeutic opportunities","volume":"89","author":"E. D. Mock","year":"2022","journal-title":"Progress in Lipid Research"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2004.03.001"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.2174\/1566524014666140414204100"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.241"},{"issue":"10","key":"30","first-page":"7076","article-title":"Follicular lymphoma mimicking marginal zone lymphoma in lymph node: a case report","volume":"7","author":"I. Matsuda","year":"2014","journal-title":"International Journal of Clinical and Experimental Pathology"}],"container-title":["PPAR Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ppar\/2023\/8456833.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ppar\/2023\/8456833.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ppar\/2023\/8456833.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:05:18Z","timestamp":1687824318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/ppar\/2023\/8456833\/"}},"subtitle":[],"editor":[{"given":"Shaolei","family":"Teng","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,6,26]]},"references-count":30,"alternative-id":["8456833","8456833"],"URL":"https:\/\/doi.org\/10.1155\/2023\/8456833","relation":{},"ISSN":["1687-4765","1687-4757"],"issn-type":[{"value":"1687-4765","type":"electronic"},{"value":"1687-4757","type":"print"}],"subject":[],"published":{"date-parts":[[2023,6,26]]}}}