Expression, Prognosis, and Regulation of ULBP1, ULBP2, and ULBP3  in Human Breast Cancer

Expression, Prognosis, and Regulation of ULBP1, ULBP2, and ULBP3 in Human Breast Cancer | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Expression, Prognosis, and Regulation of ULBP1, ULBP2, and ULBP3 in Human Breast Cancer Yutong Zhang, Caixia Han, Enze Shao, Litao Sun, Dongzhe Liu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-574086/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 The expression of NKG2D ligands (NKG2DLs), induced by stress or malignant transformation, is considered to mark dysfunctional cells for elimination by NK cells or cytotoxic lymphocytes via NKG2D/NKG2DLs pathway. ULBP1, ULBP2, and ULBP3 (ULBP1-3), three members of NKG2DLs, are common expressed in breast cancer. We analyzed the expression of ULBP1-3 in breast cancer and healthy control tissues with several databases, and found that breast cancer had a higher mRNA level of ULBP1 and ULBP2, and a higher protein level of ULBP1-3. Analysis with the bc-GenExMiner database showed that the expression of ULBP1-3 were down-regulated by the wild type P53, PR, and HER2+ in breast cancer. Except for ULBP1, ULBP2 and ULBP3 were associated with poor prognosis in breast cancer. The analysis of the correlated genes suggested that ULBP1-3 have some common pathways including NK cell-mediated cytotoxicity, microRNA in cancer, and IL-17 signaling pathway, whereas they also have their own pathways. But ULBP1-3 expression were also a significantly negative correlation with few immune markers on NK and central memory CD8+ T. The correlations and co-occurrence between ULBP1-3 and the other ligands by using TIMER and cbioportal databases showed the same form proteins or the proteins in the same family were more likely to change at the same time. Together with all these findings, increased ULBP2 and ULBP3 were correlated with poor prognosis and various markers on immune cells. These conclusions indicated that ULBP2 and ULBP3 could serve as potential biomarkers to assess prognosis and they were strong correlation with various markers in immune cells. Cancer Biology breast cancer NKG2D NKG2D ligands prognosis immune cell Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Full Text Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF. Supplementary Files FigS1.png Supplemental Figure1 ULBP1-3 expression in ER and PR combinations 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies 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-574086","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":32439643,"identity":"09af7371-ddd4-49f8-96dc-9496a4179585","order_by":0,"name":"Yutong Zhang","email":"","orcid":"https://orcid.org/0000-0003-4803-5010","institution":"Harbin Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yutong","middleName":"","lastName":"Zhang","suffix":""},{"id":32439644,"identity":"abef5f7b-fdf3-4c9f-8e15-b0706a79276f","order_by":1,"name":"Caixia Han","email":"","orcid":"","institution":"Shenzhen University General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Caixia","middleName":"","lastName":"Han","suffix":""},{"id":32439645,"identity":"05b50f70-fd90-434b-8d0a-4ae839b6d870","order_by":2,"name":"Enze Shao","email":"","orcid":"","institution":"Harbin Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Enze","middleName":"","lastName":"Shao","suffix":""},{"id":32439646,"identity":"6eb9cb9c-fbf5-4fa8-bf77-f8cbde6cf259","order_by":3,"name":"Litao Sun","email":"","orcid":"","institution":"Shenzhen University General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Litao","middleName":"","lastName":"Sun","suffix":""},{"id":32439647,"identity":"0ce6042d-aa20-4270-bb24-671bd72c2482","order_by":4,"name":"Dongzhe Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYDCCA0DM2MAgw8bAfAAhQowWHjYGtgQStTAw8BgQp4XveO/hlz932PDwSeR8/vizjUGO70YC4+cCPFokz5xLs5A8k8bDJpG7TUKyjcFY8kYCs/QMPFoMbuSYGRi2HQZrYTBsY0jccCOBjZmHkJbEtv9ALTmPPyS2MdQTo8X4wcG2AyAtDBIH2xgSDAhpkTxzxoyxsS2Zh43nmZlkwzkJw5lnHjZL49PCd7zHGBhQdnLy7cmPP/4os5HnO5588DM+LUDAJoHEAbGB0UQAMH8gpGIUjIJRMApGOAAAjXpLvclVVy0AAAAASUVORK5CYII=","orcid":"","institution":"Shenzhen University General Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Dongzhe","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2021-05-29 22:17:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-574086/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-574086/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":10344129,"identity":"cc43151a-eca9-4a23-a5ab-893aaa2594f2","added_by":"auto","created_at":"2021-06-14 16:12:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":134986,"visible":true,"origin":"","legend":"ULBP1, ULBP2, and ULBP3 expression in breast cancer and normal\ntissues. (A), NKG2DLs expression in the Oncomine database. (B), ULBP1, ULBP2,\nand ULBP3 expression expression in the TIMER databas","description":"","filename":"Fig01.png","url":"https://assets-eu.researchsquare.com/files/rs-574086/v1/53fb27a32dfc2b42a7de4581.png"},{"id":10344287,"identity":"37b204ef-156a-497d-b681-90c136b9a273","added_by":"auto","created_at":"2021-06-14 16:15:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":561785,"visible":true,"origin":"","legend":"IHC images of ULBP1, ULBP2, and ULBP3 detected in the HPA","description":"","filename":"Fig02.png","url":"https://assets-eu.researchsquare.com/files/rs-574086/v1/731488039800366c71fa72dd.png"},{"id":10344288,"identity":"6ec98a6a-7bf4-4d93-bbd0-9225e7b22686","added_by":"auto","created_at":"2021-06-14 16:15:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":181534,"visible":true,"origin":"","legend":"Clinical significance of ULBP1-3 in breast cancer patients. (A-C), Survival\ncurves of OS, PPS, and DMFS for ULBP1 in breast cancer, respectively; (D-F),\nSurvival curves of OS, PPS, and DMFS for ULBP2 in breast cancer, respectively;\n(G-I), Survival curves of OS, PPS, and DMFS for ULBP2 in breast cancer,\nrespectively","description":"","filename":"Fig03.png","url":"https://assets-eu.researchsquare.com/files/rs-574086/v1/c1fa293499c55ca7d6ea1e50.png"},{"id":10344127,"identity":"9800787b-a25c-41ad-9894-78c2056dddd4","added_by":"auto","created_at":"2021-06-14 16:12:45","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":94173,"visible":true,"origin":"","legend":"Significantly enriched KEGG pathways of ULBP1-3 in breast cancer\npatients (FDR\u003c0.05). (A), KEGG pathways of ULBP1; (B), KEGG pathways of\nULBP2; (C), KEGG pathways of ULBP3","description":"","filename":"Fig04.png","url":"https://assets-eu.researchsquare.com/files/rs-574086/v1/6b5607bcef6f06c949dbe899.png"},{"id":10344465,"identity":"8b3014b5-6ecc-4d09-8472-ff59c2fefe8c","added_by":"auto","created_at":"2021-06-14 16:18:45","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":434551,"visible":true,"origin":"","legend":"Correlation of NKG2DLs expression with immune infiltration level in breast\ncancer cohort","description":"","filename":"Fig05.png","url":"https://assets-eu.researchsquare.com/files/rs-574086/v1/4cb827f60d96ea3a93057ed8.png"},{"id":10344132,"identity":"624eb00e-9ca9-442f-900b-67d7c282816b","added_by":"auto","created_at":"2021-06-14 16:12:45","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":696573,"visible":true,"origin":"","legend":"Correlation analysis between ULBP1-3 and immune markers of various\nimmune cells. *, p\u003c0.05","description":"","filename":"Fig06.png","url":"https://assets-eu.researchsquare.com/files/rs-574086/v1/2b5f60b58329ab3fe4ebbf1a.png"},{"id":10343736,"identity":"9bf9e4d4-ad43-40ef-8109-fc1a115a16c2","added_by":"auto","created_at":"2021-06-14 16:09:45","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":87782,"visible":true,"origin":"","legend":"The correlations and interaction between ULBP1-3 and five other ligands","description":"","filename":"Fig07.png","url":"https://assets-eu.researchsquare.com/files/rs-574086/v1/0d4a00f3e8de0cf0d4dc4a3e.png"},{"id":13645980,"identity":"1117fe6e-94b1-4988-85c3-c118b0f08acd","added_by":"auto","created_at":"2021-09-17 09:22:03","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2048538,"visible":true,"origin":"","legend":"","description":"","filename":"Liumaintext.pdf","url":"https://assets-eu.researchsquare.com/files/rs-574086/v1_covered.pdf"},{"id":10343739,"identity":"2c470048-2412-4bf4-9bca-24fe6fb1d7e2","added_by":"auto","created_at":"2021-06-14 16:09:52","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1718545,"visible":true,"origin":"","legend":"","description":"","filename":"Liumaintext.pdf","url":"https://assets-eu.researchsquare.com/files/rs-574086/v1_covered.pdf"},{"id":10343730,"identity":"fcb661d3-2366-4db0-900e-80b2b0f06192","added_by":"auto","created_at":"2021-06-14 16:09:45","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":185335,"visible":true,"origin":"","legend":"Supplemental Figure1 ULBP1-3 expression in ER and PR combinations","description":"","filename":"FigS1.png","url":"https://assets-eu.researchsquare.com/files/rs-574086/v1/c0c5e79e51f392097fb3ca9b.png"}],"financialInterests":"","formattedTitle":"Expression, Prognosis, and Regulation of ULBP1, ULBP2, and ULBP3 in Human Breast Cancer","fulltext":[{"header":"Full Text","content":"\u003cp\u003eDue to technical limitations, full-text HTML conversion of this manuscript could not be completed. 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ULBP1, ULBP2, and ULBP3 (ULBP1-3), three members of NKG2DLs, are common expressed in breast cancer. We analyzed the expression of ULBP1-3 in breast cancer and healthy control tissues with several databases, and found that breast cancer had a higher mRNA level of ULBP1 and ULBP2, and a higher protein level of ULBP1-3. Analysis with the bc-GenExMiner database showed that the expression of ULBP1-3 were down-regulated by the wild type P53, PR, and HER2+ in breast cancer. Except for ULBP1, ULBP2 and ULBP3 were associated with poor prognosis in breast cancer. The analysis of the correlated genes suggested that ULBP1-3 have some common pathways including NK cell-mediated cytotoxicity, microRNA in cancer, and IL-17 signaling pathway, whereas they also have their own pathways. But ULBP1-3 expression were also a significantly negative correlation with few immune markers on NK and central memory CD8+ T. The correlations and co-occurrence between ULBP1-3 and the other ligands by using TIMER and cbioportal databases showed the same form proteins or the proteins in the same family were more likely to change at the same time. Together with all these findings, increased ULBP2 and ULBP3 were correlated with poor prognosis and various markers on immune cells. These conclusions indicated that ULBP2 and ULBP3 could serve as potential biomarkers to assess prognosis and they were strong correlation with various markers in immune cells.","manuscriptTitle":"Expression, Prognosis, and Regulation of ULBP1, ULBP2, and ULBP3 in Human Breast Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-06-14 16:09:43","doi":"10.21203/rs.3.rs-574086/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":"e5dfffd1-157e-4dd3-9176-a81f1ab1e027","owner":[],"postedDate":"June 14th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":5010022,"name":"Cancer Biology"}],"tags":[],"updatedAt":"2021-06-14T16:09:44+00:00","versionOfRecord":[],"versionCreatedAt":"2021-06-14 16:09:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-574086","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-574086","identity":"rs-574086","version":["v1"]},"buildId":"omnImTCwR2MFx8CMYfrG7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}