Expression Characteristics, Prognostic Value, and Immune-Related Analysis of PPP2R1A in Lung Adenocarcinoma

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Abstract

Abstract Lung adenocarcinoma (LUAD) is a major subtype of lung cancer with poor prognosis. This study investigates the expression, prognostic significance, and functional role of the PPP2R1A gene in LUAD. Using the Xiantao Academic Online tool, we observed a significant upregulation of PPP2R1A in 26 cancers, including LUAD, confirmed by both unpaired and paired analysis ( P  < 0.05). The diagnostic potential of PPP2R1A in LUAD was modest, with an AUC of 0.593. Kaplan-Meier survival analysis revealed that overexpression of PPP2R1A was associated with poor progression-free survival (FP) and overall survival (OS) in LUAD patients, particularly in early-stage disease ( P  < 0.05). Subgroup analysis indicated a significant correlation between PPP2R1A expression and clinical features such as N stage and tumor stage, with higher expression in advanced-stage LUAD. A protein-protein interaction (PPI) network identified key interaction partners of PPP2R1A, including PRPF31 and SCAF1, and functional enrichment analysis highlighted roles in protein dephosphorylation, cell cycle regulation, and metabolic pathways. Moreover, the genetic mutation frequency of PPP2R1A was low (2.3%), with missense mutations in the phosphatase domain. Immunoinfiltration analysis revealed significant correlations between PPP2R1A expression and macrophage infiltration, as well as the presence of regulatory T cells, suggesting a potential immunomodulatory role in LUAD. Functional assays showed that PPP2R1A knockdown significantly inhibited the proliferation, invasion, and metastasis of LUAD cells, further supporting its role in tumor progression. These findings suggest that PPP2R1A plays a critical role in LUAD pathogenesis and may serve as a potential diagnostic and therapeutic target.
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Expression Characteristics, Prognostic Value, and Immune-Related Analysis of PPP2R1A in Lung Adenocarcinoma | 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 Expression Characteristics, Prognostic Value, and Immune-Related Analysis of PPP2R1A in Lung Adenocarcinoma Mingyou Dong, Yuhong Hu, Shanshan Xiao, Pei Ouyang, Yuejiao Huang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7734708/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 Lung adenocarcinoma (LUAD) is a major subtype of lung cancer with poor prognosis. This study investigates the expression, prognostic significance, and functional role of the PPP2R1A gene in LUAD. Using the Xiantao Academic Online tool, we observed a significant upregulation of PPP2R1A in 26 cancers, including LUAD, confirmed by both unpaired and paired analysis ( P < 0.05). The diagnostic potential of PPP2R1A in LUAD was modest, with an AUC of 0.593. Kaplan-Meier survival analysis revealed that overexpression of PPP2R1A was associated with poor progression-free survival (FP) and overall survival (OS) in LUAD patients, particularly in early-stage disease ( P < 0.05). Subgroup analysis indicated a significant correlation between PPP2R1A expression and clinical features such as N stage and tumor stage, with higher expression in advanced-stage LUAD. A protein-protein interaction (PPI) network identified key interaction partners of PPP2R1A, including PRPF31 and SCAF1, and functional enrichment analysis highlighted roles in protein dephosphorylation, cell cycle regulation, and metabolic pathways. Moreover, the genetic mutation frequency of PPP2R1A was low (2.3%), with missense mutations in the phosphatase domain. Immunoinfiltration analysis revealed significant correlations between PPP2R1A expression and macrophage infiltration, as well as the presence of regulatory T cells, suggesting a potential immunomodulatory role in LUAD. Functional assays showed that PPP2R1A knockdown significantly inhibited the proliferation, invasion, and metastasis of LUAD cells, further supporting its role in tumor progression. These findings suggest that PPP2R1A plays a critical role in LUAD pathogenesis and may serve as a potential diagnostic and therapeutic target. lung adenocarcinoma PPP2R1A tumor microenvironment immune infiltration Kaplan-Meier Plotter 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Adenocarcinoma","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":"lung adenocarcinoma, PPP2R1A, tumor microenvironment, immune infiltration, Kaplan-Meier Plotter","lastPublishedDoi":"10.21203/rs.3.rs-7734708/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7734708/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLung adenocarcinoma (LUAD) is a major subtype of lung cancer with poor prognosis. This study investigates the expression, prognostic significance, and functional role of the PPP2R1A gene in LUAD. Using the Xiantao Academic Online tool, we observed a significant upregulation of PPP2R1A in 26 cancers, including LUAD, confirmed by both unpaired and paired analysis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The diagnostic potential of PPP2R1A in LUAD was modest, with an AUC of 0.593. Kaplan-Meier survival analysis revealed that overexpression of PPP2R1A was associated with poor progression-free survival (FP) and overall survival (OS) in LUAD patients, particularly in early-stage disease (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Subgroup analysis indicated a significant correlation between PPP2R1A expression and clinical features such as N stage and tumor stage, with higher expression in advanced-stage LUAD. A protein-protein interaction (PPI) network identified key interaction partners of PPP2R1A, including PRPF31 and SCAF1, and functional enrichment analysis highlighted roles in protein dephosphorylation, cell cycle regulation, and metabolic pathways. Moreover, the genetic mutation frequency of PPP2R1A was low (2.3%), with missense mutations in the phosphatase domain. Immunoinfiltration analysis revealed significant correlations between PPP2R1A expression and macrophage infiltration, as well as the presence of regulatory T cells, suggesting a potential immunomodulatory role in LUAD. Functional assays showed that PPP2R1A knockdown significantly inhibited the proliferation, invasion, and metastasis of LUAD cells, further supporting its role in tumor progression. These findings suggest that PPP2R1A plays a critical role in LUAD pathogenesis and may serve as a potential diagnostic and therapeutic target.\u003c/p\u003e","manuscriptTitle":"Expression Characteristics, Prognostic Value, and Immune-Related Analysis of PPP2R1A in Lung Adenocarcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-05 17:51:34","doi":"10.21203/rs.3.rs-7734708/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":"488714c7-065c-4b5d-be25-b6d3027cc6ba","owner":[],"postedDate":"December 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-04T10:28:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-05 17:51:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7734708","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7734708","identity":"rs-7734708","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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