{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T20:10:34Z","timestamp":1787688634972,"version":"build-2784847793"},"reference-count":31,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T00:00:00Z","timestamp":1593993600000},"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":["81874123"],"award-info":[{"award-number":["81874123"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772709"],"award-info":[{"award-number":["81772709"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chromosomal rearrangements are common in clear cell renal cell carcinoma (ccRCC) and their roles in mediating sensitivity to tyrosine kinase inhibitors (TKIs) and mTOR inhibitors (mTORi) remain elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We developed an in silico strategy by screening copy number variance (CNV) that was potentially related to TKI or mTORi sensitivity in ccRCC by reproducing the TCGA and GDSC datasets. Candidate genes should be both significantly prognostic and related to drug sensitivity or resistance, and were then validated in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ADCYAP1 loss and GNAS gain were associated with sensitivity and resistance and to Cabozantinib, respectively. ACRBP gain and CTBP1 loss were associated with sensitivity and resistance and to Pazopanib, respectively. CDKN2A loss and SULT1A3 gain were associated with sensitivity and resistance and to Temsirolimus, respectively. CCNE1 gain was associated with resistance to Axitinib and LRP10 loss was associated with resistance to Sunitinib. Mutivariate analysis showed ADCYAP1, GNAS, and CCNE1 remained independently prognostic when adjusted for the rest.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Here we show CNVs of several genes that are associated with sensitivity and resistance to commonly used TKIs and mTORi in ccRCC. Further validation and functional analyses are therefore needed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.3281","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T17:49:07Z","timestamp":1594057747000},"page":"6020-6029","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Comprehensive analysis of copy number variance and sensitivity to common targeted therapy in clear cell renal cell carcinoma: In silico analysis with in vitro validation"],"prefix":"10.1002","volume":"9","author":[{"given":"Yuqing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Urology Huashan Hospital Fudan University Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7018-6838","authenticated-orcid":false,"given":"Yanyun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Dermatology Huashan Hospital Fudan University Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhidong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Huashan Hospital Fudan University Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Urology Huashan Hospital Fudan University Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1854-356X","authenticated-orcid":false,"given":"Chenchen","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Urology Huashan Hospital Fudan University Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.9"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3844"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.59"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2760"},{"key":"e_1_2_10_6_1","first-page":"7","article-title":"Tumor copy number alteration burden is a pan\u2010cancer prognostic factor associated with recurrence and death","author":"Hieronymus H","year":"2018","journal-title":"Elife"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.209"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176659"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2699"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20220"},{"issue":"6","key":"e_1_2_10_11_1","first-page":"1518","article-title":"TFPI\u20102 expression is decreased in bladder cancer and is related to apoptosis","volume":"21","author":"Feng C","year":"2016","journal-title":"J BUON"},{"issue":"6","key":"e_1_2_10_12_1","first-page":"619","article-title":"The origin and function of the pituitary adenylate cyclase\u2010activating polypeptide (PACAP)\/glucagon superfamily","volume":"21","author":"Sherwood NM","year":"2000","journal-title":"Endocr Rev"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1317.079"},{"key":"e_1_2_10_14_1","unstructured":"https:\/\/www.genecards.org\/Search\/Keyword?queryString=AXL%26sort=Symbol%26sortdir=Descending%26startPage=188%26pageSize=25. 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