Pan-cancer analysis reveals potential of RRM2 as a prognostic and immunological biomarker in human cancer

Pan-cancer analysis reveals potential of RRM2 as a prognostic and immunological biomarker in human 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pan-cancer analysis reveals potential of RRM2 as a prognostic and immunological biomarker in human cancer Xiaojing Ma, Zhixiang Guo, Xiaoping Xia This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5704817/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 Increasing evidence suggests that RRM2 plays an important role in cancer onset, development and progression. However, the biological significance of RRM2 in pan-cancer is unclear.In this study, the expression profile and prognostic significance of RRM2 were comprehensively investigated for the first time using bioinformatics techniques, as well as the relationship between RRM2 and clinicopathologic parameters and immune cell infiltration.This study is the first to conduct a pan-cancer analysis of RRM2 for aiding the diagnosis and treatment of cancer. Methods We comprehensively studied the expression level of RRM2, patient prognosis and its relationship with clinicopathological parameters and immune cell infiltration using bioinformatics techniques.We thoroughly analyzed the function of RRM2 in cancer through the Cancer Genome Atlas (TCGA) and Genotype-Tissue expression (GTEx) databases. Multiple web softwares and platforms were used for data analysis, including HPA,Cytoscape, GEPIA2.0, UALCAN, STRING, CancerSEA and so on. Results The results suggest that RRM2 was significantly upregulated in a variety of tumors and is associated with prognosis.Pan-cancer analysis showed that high RRM2 expression was associated with disease-free survival (DFS) and overall survival (OS) in a variety of tumors.The mRNA expression of RRM2 was related to the infiltration of various immune cells, including DC, nTreg, iTreg, Monocyte and B cells. Finally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were used to explore the role of RRM2 in pan-cancer. Conclusion RRM2 is recognized as a promising target for diagnosis, treatment and prognosis prediction and is critical for DNA replication and cancer cell proliferation. RRM2 pan-cancer biological functions prognosis immune Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Full Text Additional Declarations No competing interests reported. Table 1 is available in the Supplementary Files section. Supplementary Files Table.docx supplementaryfigure.pdf 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 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-5704817","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":396314697,"identity":"38e33487-4295-4b24-b7bd-9bd7ba7a1903","order_by":0,"name":"Xiaojing Ma","email":"","orcid":"","institution":"the fourth affiliated hospital of Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Xiaojing","middleName":"","lastName":"Ma","suffix":""},{"id":396314698,"identity":"026a480f-d578-4189-b5a0-abd33c0dc9d4","order_by":1,"name":"Zhixiang Guo","email":"","orcid":"","institution":"the fourth affiliated hospital of Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Zhixiang","middleName":"","lastName":"Guo","suffix":""},{"id":396314699,"identity":"0201c569-f7c3-4127-962f-3ba8ce8ad3fe","order_by":2,"name":"Xiaoping Xia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYDACZhBhAGYwPmDgAfESiNfCbECcFiTAJgGhCWgxOM788HFBwR27DceZn1X+kDnMwM+eY8DwcwduLZLNbMbGMwyeJc9sZjO7IcFzmEGy540BY+8Z3Fr4mRnMpHkMDieDGDcMgFoMbuQYMDO24XE/M/s3sBYQoyABqMWekBZ+Zh6wLXYgBsMBkC0SBLRINvMUA/1yOAHEkGzgSeeROPOs4GAvHi0G549vfFzw57A9iPHxZ4+1HH978sYHP/FoAQFQbCY2gFiMPZDIPIBfA0SLPYT5g5DaUTAKRsEoGIkAABcHRmm3GhBXAAAAAElFTkSuQmCC","orcid":"","institution":"the fourth affiliated hospital of Zhejiang University","correspondingAuthor":true,"prefix":"","firstName":"Xiaoping","middleName":"","lastName":"Xia","suffix":""}],"badges":[],"createdAt":"2024-12-24 08:38:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5704817/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5704817/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72794275,"identity":"f8dbe7c2-2936-469c-b723-d1a8e07431ed","added_by":"auto","created_at":"2025-01-02 08:50:49","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":96599,"visible":true,"origin":"","legend":"\u003cp\u003eExpression of RRM2 in normal human organs and tissues. (A) Human RRM2 mRNA and protein expression in organs and tissues; (B) Summary of RRM2 mRNA expression in different human organs and tissues; (C) A summary of RRM2 protein expression in different organs and tissues of the human body.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/e247c321da6fb96f97f954c6.jpg"},{"id":72794273,"identity":"1fbb82e5-6d66-4bb3-842e-e9b665013840","added_by":"auto","created_at":"2025-01-02 08:50:49","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":240138,"visible":true,"origin":"","legend":"\u003cp\u003eRRM2expression in various tumor tissues.(A) RRM2expression levels in pan-cancer from TCGA database were analyzed by TIMER2.0.(*\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05, **\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01, ***\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001). (B) Differences in RRM2 expression between tumors and normal tissues from the TCGA and GTEx databases (*\u003cem\u003ep\u003c/em\u003e\u0026lt;0.05, **\u003cem\u003ep\u003c/em\u003e\u0026lt;0.01, ***\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001). (C) The correction between RRM2expression and the pathological stages of BRCA, PAAD, KIRC andLUAD using the GEPIA2 database.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/83aba4d55dcc37a6c033b30e.jpg"},{"id":72794290,"identity":"8a29243b-a9b3-451a-ab54-08fe23a62b53","added_by":"auto","created_at":"2025-01-02 08:50:50","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":177280,"visible":true,"origin":"","legend":"\u003cp\u003eThe expression of RRM2 in pan-cancer in different databases. (A) RRM2expression in LIHC, LUAD and STAD from the HPA database. (C) Immunofluorescence staining of the subcellular localization of RRM2in HPA database. (*\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05; **\u003cem\u003e p\u003c/em\u003e \u0026lt; 0.01; *** \u003cem\u003ep \u003c/em\u003e\u0026lt;0.001, ns: no statistical differences) .\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/abf61c69b64a4d3a125fd39c.jpg"},{"id":72794271,"identity":"37f77841-8029-4f2e-b06b-48b8dd975bd4","added_by":"auto","created_at":"2025-01-02 08:50:49","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":132104,"visible":true,"origin":"","legend":"\u003cp\u003eRelationship between RRM2 expression and patient prognosis of different cancers based on the TCGA data. (A) OS map and Kaplan-Meier curves of TCGA cancers by RRM2 gene expression using gene expression profiling interactive analysis 2(GEPIA2). (B) DFS map and Kaplan-Meier curves of TCGA cancers by RRM2 gene expression using GEPIA2.\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/968724c253ce6c348060c4e3.jpg"},{"id":72794277,"identity":"33c8d366-ac28-4472-afd3-b5de4544212a","added_by":"auto","created_at":"2025-01-02 08:50:49","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":106619,"visible":true,"origin":"","legend":"\u003cp\u003eLevels of promoter methylation of RRM2 in cancers. A comparison of RRM2 methylation values between normal and primary tumor tissues was performed using the UALCAN tool.\u003c/p\u003e","description":"","filename":"Picture5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/647f81454e0abcbb585c9a3d.jpg"},{"id":72794276,"identity":"01508c4b-81d3-4e05-964d-4ee291ec074e","added_by":"auto","created_at":"2025-01-02 08:50:49","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":120297,"visible":true,"origin":"","legend":"\u003cp\u003eA heatmap showing the correlation between immune infiltration and RRM2 expression in different cancers. (*\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05; **\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01).\u003c/p\u003e","description":"","filename":"Picture6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/7f692a49574a75b13b41610d.jpg"},{"id":72794289,"identity":"56d2bf70-09c2-4287-ae49-084bf98d707d","added_by":"auto","created_at":"2025-01-02 08:50:50","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":176444,"visible":true,"origin":"","legend":"\u003cp\u003eA correlation between RRM2 expression and immune infiltration of CD8+ T cells and B cells was analyzed on the basis of 22 immune cell types. Explore potential correlations between RRM2 gene expression levels and B cell (A) and CD8+ T cell (C) infiltrationin all types of cancer in the TCGA. Infiltration of immune cells by B cells (B) and CD8+ T cells (D) in certain types of tumors.\u003c/p\u003e","description":"","filename":"Picture7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/7870683551b94e818970e984.jpg"},{"id":72794286,"identity":"4c5ed712-95c6-4b97-8747-a7989398d5f0","added_by":"auto","created_at":"2025-01-02 08:50:50","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":137242,"visible":true,"origin":"","legend":"\u003cp\u003eThe correlation between RRM2 expression and immune infiltration of cancer associated fibroblasts was examined using 22 immune cell types. (A)Various algorithms were used to explore potential associations between the level of RRM2 gene expression and the level of cancer-associated fibroblast infiltration in all types of cancer at TCGA.(B) Immune infiltration of cancer-associated fibroblasts in specific tumor types.\u003c/p\u003e","description":"","filename":"Picture8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/a4e80b3d067ef70917d6defa.jpg"},{"id":72794282,"identity":"b237d94f-73d6-4a1b-bc6a-20fdbd5b75bf","added_by":"auto","created_at":"2025-01-02 08:50:49","extension":"jpg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":141377,"visible":true,"origin":"","legend":"\u003cp\u003eFunction of RRM2 in single cell function analysis from CancerSEA database.(A) Functional status of RRM2 in different human cancers. (B) Correlation analysis of RRM2 with functional status of AML, LUAD, BRCA, glioma, MEL, HNSCC, CRC and UM. (* \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05, **\u003cem\u003e p \u003c/em\u003e\u0026lt; 0.01,*** \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001).\u003c/p\u003e","description":"","filename":"Picture9.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/586ab22a3e9e0497ca8e42d4.jpg"},{"id":72794288,"identity":"33031411-3887-4115-a60d-5578e2e9e3d5","added_by":"auto","created_at":"2025-01-02 08:50:50","extension":"jpg","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":205502,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation of RRM2 with TILs and immunomodulation-related genes in 30 cancers. Correlation between RRM2 expression and (A)TILs, (B) immunostimulators, (C) immunosuppressive factors, (D)MHC molecules, (E) chemokines, and (F) chemokine receptors. (* \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05, **\u003cem\u003e p \u003c/em\u003e\u0026lt; 0.01,*** \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001).\u003c/p\u003e","description":"","filename":"Picture10.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/e6c8b11df73aa857dbeffbe2.jpg"},{"id":72794291,"identity":"bfdd5acf-e7ef-4d28-9846-42b2f229debf","added_by":"auto","created_at":"2025-01-02 08:50:50","extension":"jpg","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":141012,"visible":true,"origin":"","legend":"\u003cp\u003eEnrichment analysis of RRM2 related genes. (A-B)Existing experiments identified the RRM2-binding protein and obtained the main connections using the STRING tool. (C) Venn diagram between RRM2-binding proteins and RRM2-related genes.\u003c/p\u003e","description":"","filename":"Picture11.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/2230c23ae9796ebaa8ef8b57.jpg"},{"id":72794280,"identity":"e0973ccc-dd35-4c12-8eb6-e0356dbbe11d","added_by":"auto","created_at":"2025-01-02 08:50:49","extension":"jpg","order_by":12,"title":"Figure 12","display":"","copyAsset":false,"role":"figure","size":140915,"visible":true,"origin":"","legend":"\u003cp\u003eCo-expression of RRM2 and RRM2 related gene. (A)Expression level of top five RRM2 related genes in TCGA tumors. (B) KEGG pathway analysis based on RRM2 binding and interacting genes. (C) Enrichment analysis of RRM2 related genes cnetplot of molecular function data in GO analysis.\u003c/p\u003e","description":"","filename":"Picture12.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/0aa8859f199489e9671e905b.jpg"},{"id":81192811,"identity":"6594af2a-a41a-4d0c-8ea2-e9bcfaae8952","added_by":"auto","created_at":"2025-04-23 09:32:13","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2168891,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1_covered_41b9f393-49fa-4dd1-948a-f6f9d218f306.pdf"},{"id":72795785,"identity":"c79f795c-cd65-4b12-a81b-49c4513aa21b","added_by":"auto","created_at":"2025-01-02 08:58:49","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":14020,"visible":true,"origin":"","legend":"","description":"","filename":"Table.docx","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/b12e3016bd5ae75768deeeaf.docx"},{"id":72794274,"identity":"885daaf6-cdc7-4a5d-aa23-941427d2252b","added_by":"auto","created_at":"2025-01-02 08:50:49","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2790154,"visible":true,"origin":"","legend":"","description":"","filename":"supplementaryfigure.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5704817/v1/b7def22cd05ad68f8bc46114.pdf"}],"financialInterests":"\u003cp\u003eNo competing interests reported.\u003c/p\u003e\n\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e","formattedTitle":"Pan-cancer analysis reveals potential of RRM2 as a prognostic and immunological biomarker in human cancer","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":"RRM2, pan-cancer, biological functions, prognosis, immune","lastPublishedDoi":"10.21203/rs.3.rs-5704817/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5704817/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground Increasing evidence suggests that RRM2 plays an important role in cancer onset, development and progression. However, the biological significance of RRM2 in pan-cancer is unclear.In this study, the expression profile and prognostic significance of RRM2 were comprehensively investigated for the first time using bioinformatics techniques, as well as the relationship between RRM2 and clinicopathologic parameters and immune cell infiltration.This study is the first to conduct a pan-cancer analysis of RRM2 for aiding the diagnosis and treatment of cancer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMethods We comprehensively studied the expression level of RRM2, patient prognosis and its relationship with clinicopathological parameters and immune cell infiltration using bioinformatics techniques.We thoroughly analyzed the function of RRM2 in cancer through the Cancer Genome Atlas (TCGA) and Genotype-Tissue expression (GTEx) databases. Multiple web softwares and platforms were used for data analysis, including HPA,Cytoscape, GEPIA2.0, UALCAN, STRING, CancerSEA and so on.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults The results suggest that RRM2 was significantly upregulated in a variety of tumors and is associated with prognosis.Pan-cancer analysis showed that high RRM2 expression was associated with disease-free survival (DFS) and overall survival (OS) in a variety of tumors.The mRNA expression of RRM2 was related to the infiltration of various immune cells, including DC, nTreg, iTreg, Monocyte and B cells. Finally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were used to explore the role of RRM2 in pan-cancer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConclusion RRM2 is recognized as a promising target for diagnosis, treatment and prognosis prediction and is critical for DNA replication and cancer cell proliferation.\u003c/p\u003e","manuscriptTitle":"Pan-cancer analysis reveals potential of RRM2 as a prognostic and immunological biomarker in human cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-02 08:50:44","doi":"10.21203/rs.3.rs-5704817/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":"54d82106-d975-474a-80e0-301b1d107199","owner":[],"postedDate":"January 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-23T09:24:03+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-02 08:50:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5704817","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5704817","identity":"rs-5704817","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}