{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T14:09:35Z","timestamp":1781273375153,"version":"3.54.1"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T00:00:00Z","timestamp":1590624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571590"],"award-info":[{"award-number":["81571590"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010104","name":"Tianjin Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010104","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010104","name":"Tianjin Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010104","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010104","name":"Tianjin Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>KIT proto\u2010oncogene ligand (KITLG) is a pleiotropic factor which is found in diverse cancers and is involved in cell proliferation, differentiation, and survival. However, the value of KITLG in thymoma remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 121 thymoma samples from The Cancer Genome Atlas Thymoma (TCGA\u2010THYM) dataset were used to analyze KITLG related genome\u2010wide expression profiles, and microRNA profiles and methylation alterations and a GEO dataset\u2010GSE29695, including 37 samples was used as verification. For cell\u2010based studies, specific small interfering RNA targeting KITLG or a KITLG overexpression vector were used to clarify the changes of the MAPK pathway in an AB thymoma cell line Thy0517.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both datasets showed that high expression of KITLG was significantly associated with type A and AB thymoma. Through multiomic analysis of the TCGA\u2010THYM, it was found that with the high expression of KITLG, there were 220 upregulated and 72 downregulated genes at the mRNA level, 79 positive and 78 negative miRNAs, 28 hypermethylation and 163 hypomethylation regions. In the thymoma cell line Thy0517, it was found that the expression of GRB2 and the phosphorylation levels of BRAF, MEK1\/2, and ERK1\/2 in the MAPK pathway were positively correlated with the change in KITLG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>High expression of KITLG is a new hallmark of WHO type A and AB thymomas in which it might play a critical role through the activation of the MAPK signaling pathway. Additionally, it is hoped that KITLG will become a potential target for the diagnosis of type A and AB thymoma through further research in the future.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><\/jats:sec><jats:sec><jats:title>Significant findings of the study<\/jats:title><jats:p>KIT proto\u2010oncogene ligand (KITLG) is a new hallmark of type A and AB thymomas which induce a series of aberrant alteration of mRNA, miRNA and DNA methylation. The expression of KITLG is significantly higher in type A and AB than other subtypes of thymoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>What this study adds<\/jats:title><jats:p>KITLG activated the MAPK signaling pathway to promote type A and AB thymoma which might be a potential diagnostic biomarker or target.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.13486","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T13:04:23Z","timestamp":1590671063000},"page":"1944-1954","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["High expression of <scp>KITLG<\/scp> is a new hallmark activating the <scp>MAPK<\/scp> pathway in type A and <scp>AB<\/scp> thymoma"],"prefix":"10.1111","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9239-1461","authenticated-orcid":false,"given":"Zhaoyu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanguo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyou","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5863-2700","authenticated-orcid":false,"given":"Kai","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2018.10.001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2017.06.072"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2014.04.028"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)71181-7"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msy136"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1958-6"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00031-10"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.196931"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.12163"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042669"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.425"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4191"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002392"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2015.09.016"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.111641"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1340"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-02-835561"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MP.0000032534.81894.B3"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2016.02.005"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16162-2"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27950"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6328"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9595718"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.01.008"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2212"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2010.10.017"},{"key":"e_1_2_7_29_1","first-page":"3971259","article-title":"A meta\u2010analysis of the association between DNMT1 polymorphisms and cancer risk","volume":"2017","author":"Li H","year":"2017","journal-title":"Biomed Res Int"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.25297"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3016"},{"key":"e_1_2_7_32_1","unstructured":"RadovichM PickeringCR FelauIet al. The integrated genomic landscape of thymic epithelial tumors. Cancer Cell 2018;33:244\u2013258.e10."},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.06.180"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-007-9759-7"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.04.141"}],"container-title":["Thoracic Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1759-7714.13486","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.13486","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1759-7714.13486","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.13486","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T13:56:49Z","timestamp":1693922209000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1759-7714.13486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,28]]},"references-count":34,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1111\/1759-7714.13486"],"URL":"https:\/\/doi.org\/10.1111\/1759-7714.13486","archive":["Portico"],"relation":{},"ISSN":["1759-7706","1759-7714"],"issn-type":[{"value":"1759-7706","type":"print"},{"value":"1759-7714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,28]]},"assertion":[{"value":"2020-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}