Clinical value and in vitro validation of gene and molecular subtype identification in renal clear cell carcinoma

Clinical value and in vitro validation of gene and molecular subtype identification in renal clear cell carcinoma | 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 Clinical value and in vitro validation of gene and molecular subtype identification in renal clear cell carcinoma Jun Chen, Changjiu Li, Kun Shang, Chao Chen, Huadong He, Gang Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6872158/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 Clear cell renal cell carcinoma (ccRCC) constitutes a widespread and relentlessly aggressive malignancy of the urinary tract, distinguished by its high lethality and pronounced propensity for metastatic dissemination. Despite advancements in genomic therapy, the efficacy of targeted treatment for drug-resistant ccRCC remains limited, underscoring the need for robust prognostic indicators to enhance disease management. Method We utilized transcriptome data from the TCGA-KIRC and GEO cohorts to investigate gene expression disparities in ccRCC. Employing nonnegative matrix factorization, we segregated samples into specific molecular subgroups. Genes with prognostic significance were determined through both univariate and multivariate Cox proportional hazards analyses. Subsequently, we constructed a scoring algorithm to estimate patient risk and evaluated its discriminative ability via ROC curves alongside calibration charts. The model's immunotherapeutic significance was assessed through the immune phenotype score (IPS), and the sensitivity to chemotherapeutic drugs was evaluated. Result Our analysis identified seven core genes associated with ccRCC prognosis. This gene‑centred risk stratification framework bifurcated the cohort into high‑risk (HRG) and low‑risk (LRG) strata, revealing pronounced disparities in overall survival. Its prognostic fidelity was underscored by areas under the receiver operating characteristic curves of 0.88, 0.82 and 0.81 for 1, 3 and 5 - year survival projections, respectively. Functional enrichment analysis illuminated the principal biological processes and signaling pathways modulated by these genes, and the model's predictive accuracy was further confirmed through calibration curves. Conclusion Derived from ccRCC‑related gene signatures, this prognostic framework serves as a robust instrument for forecasting clinical outcomes and informing individualized therapeutic strategies. The model's predictive power, combined with its ability to assess immune cell infiltration and response to chemotherapy, offers a comprehensive approach to ccRCC management in clinical practice. prognostic model Clear cell renal cell carcinoma bioinformatics immunotherapy personalized medicine Full Text Additional Declarations No competing interests reported. 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-6872158","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":498300610,"identity":"9f0cc52f-de12-47c9-93dd-48a65240216f","order_by":0,"name":"Jun Chen","email":"","orcid":"","institution":"Zhejiang Chinese Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Chen","suffix":""},{"id":498300611,"identity":"6f5ef57d-2160-40b4-a335-34a084fd9cb5","order_by":1,"name":"Changjiu Li","email":"","orcid":"","institution":"Westlake 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medicine","lastPublishedDoi":"10.21203/rs.3.rs-6872158/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6872158/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eClear cell renal cell carcinoma (ccRCC) constitutes a widespread and relentlessly aggressive malignancy of the urinary tract, distinguished by its high lethality and pronounced propensity for metastatic dissemination. Despite advancements in genomic therapy, the efficacy of targeted treatment for drug-resistant ccRCC remains limited, underscoring the need for robust prognostic indicators to enhance disease management.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e\u003cp\u003eWe utilized transcriptome data from the TCGA-KIRC and GEO cohorts to investigate gene expression disparities in ccRCC. Employing nonnegative matrix factorization, we segregated samples into specific molecular subgroups. Genes with prognostic significance were determined through both univariate and multivariate Cox proportional hazards analyses. Subsequently, we constructed a scoring algorithm to estimate patient risk and evaluated its discriminative ability via ROC curves alongside calibration charts. The model's immunotherapeutic significance was assessed through the immune phenotype score (IPS), and the sensitivity to chemotherapeutic drugs was evaluated.\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e\u003cp\u003eOur analysis identified seven core genes associated with ccRCC prognosis. This gene‑centred risk stratification framework bifurcated the cohort into high‑risk (HRG) and low‑risk (LRG) strata, revealing pronounced disparities in overall survival. Its prognostic fidelity was underscored by areas under the receiver operating characteristic curves of 0.88, 0.82 and 0.81 for 1, 3 and 5 - year survival projections, respectively. Functional enrichment analysis illuminated the principal biological processes and signaling pathways modulated by these genes, and the model's predictive accuracy was further confirmed through calibration curves.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eDerived from ccRCC‑related gene signatures, this prognostic framework serves as a robust instrument for forecasting clinical outcomes and informing individualized therapeutic strategies. The model's predictive power, combined with its ability to assess immune cell infiltration and response to chemotherapy, offers a comprehensive approach to ccRCC management in clinical practice.\u003c/p\u003e","manuscriptTitle":"Clinical value and in vitro validation of gene and molecular subtype identification in renal clear cell carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-12 11:28:28","doi":"10.21203/rs.3.rs-6872158/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":"ee9d57e0-0572-4b55-a748-b20d2575b6fb","owner":[],"postedDate":"August 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T08:38:20+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-12 11:28:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6872158","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6872158","identity":"rs-6872158","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}