Patient-derived renal cell carcinoma organoids for precision medicine

Patient-derived renal cell carcinoma organoids for precision medicine | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Patient-derived renal cell carcinoma organoids for precision medicine Xiaoxiao Wu, Meiyou Liu, Wanxiang Zheng, Fan Wang, Li Peng, Lianghua Cheng, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4785533/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Renal cell carcinoma (RCC) is one of the most common diseases with limited treatment options. A better understanding of this disease and treatment has been hindered by a lack of representative preclinical models. Methods: We established tumor organoids, three-dimensional cultures from clinical RCC samples. RCC organoids were characterized by H&E staining, immunohistochemical staining and whole-exome sequencing. Organoids were derived from patients treated with different drugs to test their responses to the drugs. Results: H&E staining, immunohistochemical staining and whole-exome sequencing revealed that RCC organoids recapitulated the histological feature and transcriptional profile of the parent tumor. Using the RCC organoid model, we found that RCC organoids exhibited differential responses to sunitinib, pazopanib, Cabozantinib, Lenvatinib + Everolimus, and MK6482 + Sunitinib treatment. Conclusions: Our research suggests that organoids may become a favorable model for precise drug use in RCC. renal cell carcinoma tumor organoid whole‑exome sequencing precision medicine Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Full Text Additional Declarations No competing interests reported. Tables are available in the Supplementary Files section. Supplementary Files Table1.docx Table2.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4785533","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":333687332,"identity":"1e02100e-92e9-4163-9aa7-5bba1b422cb3","order_by":0,"name":"Xiaoxiao 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University","correspondingAuthor":false,"prefix":"","firstName":"Yanyan","middleName":"","lastName":"Jia","suffix":""}],"badges":[],"createdAt":"2024-07-23 04:24:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4785533/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4785533/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63273781,"identity":"15305131-d830-4155-b8ae-efb7a97b7904","added_by":"auto","created_at":"2024-08-26 11:46:37","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":891945,"visible":true,"origin":"","legend":"\u003cp\u003eMicroscopy images of organoid lines derived from these RCC tissues.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4785533/v1/99ac2f23ceb661db81999843.jpg"},{"id":63273211,"identity":"8db7478b-bed8-425a-978b-75b18566992e","added_by":"auto","created_at":"2024-08-26 11:38:37","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1021210,"visible":true,"origin":"","legend":"\u003cp\u003eH\u0026amp;E staining of parental tumor tissue and organoids.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4785533/v1/d4136f9b7b4162aabc2d5bfd.jpg"},{"id":63272366,"identity":"99bf3683-b16b-4d36-9962-1a52a2396b49","added_by":"auto","created_at":"2024-08-26 11:30:37","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1407239,"visible":true,"origin":"","legend":"\u003cp\u003eIHC staining CAIX, CD10, CK7, KI67 and VIM in parental tumor tissue and organoids\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4785533/v1/d5f22d967178de18ea3c5df7.jpg"},{"id":63272364,"identity":"b3125291-7b01-4623-a3f0-30aac52d7f16","added_by":"auto","created_at":"2024-08-26 11:30:37","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":547716,"visible":true,"origin":"","legend":"\u003cp\u003eCNV heatmap of all samples. The X-axis represents the chromosome position, and the Y-axis represents the sample. The color scale represents the log2 value of the copy number. Log2 \u0026lt; 0 is blue, representing the decrease of the copy number; Log2 \u0026gt; 0 is red, indicating the decrease of the copy number.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4785533/v1/c2c403f301a2168c4cc884d6.jpg"},{"id":63272361,"identity":"2eebd94f-40f9-4389-a667-7fa2edc8e78a","added_by":"auto","created_at":"2024-08-26 11:30:37","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1412595,"visible":true,"origin":"","legend":"\u003cp\u003eDrug response of RCC organoids. (A) After administration, the effect of drugs on the morphology of Organoid cells. (B) The IR of drugs on organoids.\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4785533/v1/37500db0d3a8231b5bcc3ebd.jpg"},{"id":64396834,"identity":"cf0f02a7-a61b-4587-8ebd-60308f7665ad","added_by":"auto","created_at":"2024-09-12 14:45:48","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5513448,"visible":true,"origin":"","legend":"","description":"","filename":"Manscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4785533/v1_covered_cffa7435-ce2f-473f-950b-fa3cc1d0fd00.pdf"},{"id":63272360,"identity":"e3094014-d951-4d5b-aa3b-3b0d8e2c77a2","added_by":"auto","created_at":"2024-08-26 11:30:37","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":17054,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4785533/v1/bcdd0782f2513ca3df2547af.docx"},{"id":63272367,"identity":"df0f3063-7a80-4ebe-baf1-b38055ff1591","added_by":"auto","created_at":"2024-08-26 11:30:37","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":15446,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-4785533/v1/ff10272ea18619b5a9df3091.docx"}],"financialInterests":"\u003cp\u003eNo competing interests reported.\u003c/p\u003e\n\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e","formattedTitle":"Patient-derived renal cell carcinoma organoids for precision medicine","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"renal cell carcinoma, tumor organoid, whole‑exome sequencing, precision medicine","lastPublishedDoi":"10.21203/rs.3.rs-4785533/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4785533/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eRenal cell carcinoma (RCC) is one of the most common diseases with limited treatment options. A better understanding of this disease and treatment has been hindered by a lack of representative preclinical models.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe established tumor organoids, three-dimensional cultures from clinical RCC samples. RCC organoids were characterized by H\u0026amp;E staining,\u003c/p\u003e\n\u003cp\u003eimmunohistochemical staining and whole-exome sequencing. Organoids were derived from patients treated with different drugs to test their responses to the drugs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eH\u0026amp;E staining, immunohistochemical staining and whole-exome sequencing revealed that RCC organoids recapitulated the histological feature and transcriptional profile of the parent tumor. Using the RCC organoid model, we found that RCC organoids exhibited differential responses to sunitinib, pazopanib, Cabozantinib, Lenvatinib + Everolimus, and MK6482 + Sunitinib treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Our research suggests that organoids may become a favorable model for precise drug use in RCC.\u003c/p\u003e","manuscriptTitle":"Patient-derived renal cell carcinoma organoids for precision medicine","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-26 11:30:32","doi":"10.21203/rs.3.rs-4785533/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"864e0566-4759-4737-bb3b-130096185eb6","owner":[],"postedDate":"August 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-30T06:54:08+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-26 11:30:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4785533","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4785533","identity":"rs-4785533","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}