Large-Scale Transcriptome Analysis Identified Novel Ferroptosis-Related Gene Signatures for Predicting the Prognostic of Patients with Lung Adenocarcinoma

Large-Scale Transcriptome Analysis Identified Novel Ferroptosis-Related Gene Signatures for Predicting the Prognostic of Patients with 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 Large-Scale Transcriptome Analysis Identified Novel Ferroptosis-Related Gene Signatures for Predicting the Prognostic of Patients with Lung Adenocarcinoma Lei Sun, Jia Gu, Wenke Liu, Zhe Zhang, Yao Yao, Tao Han, Wenya Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-49010/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: Lung cancer is the most common of all malignant tumors. Traditional tumor staging has general sensitivity and specificity in predicting patient prognosis. Ferroptosis is a novel form of non-apoptotic form of cell death promoted by lipid peroxidation. Ferroptosis may be involved in the malignant progression of tumors through the regulation of glutathione depletion or the P53 signaling pathway. However, there are fewer studies on the impact of ferroptosis on tumor prognosis. Methods: We summarized 22 molecules that regulate ferroptosis. The transcriptome and corresponding clinical data were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The Wilcoxon test was utilized to analyze the expression of ferroptosis-related genes. We established risk score signatures, and all patients divided into two groups. Survival curves and multifactorial Cox regression analyses were performed to explore the prognostic value of ferroptosis on lung adenocarcinoma (LUAD). Results: We found that most ferroptosis-related genes are specifically expressed in LUAD tissue. We established a six‑mRNA signature and a seven‑IncRNA signature. All the models showed high predictive performance (AUC: 0.66–0.8), and patients in the low-risk group had higher overall survival than those in the high-risk group (P<0.05). The risk score is an independent risk factor for predicting the prognosis of LUAD. Conclusions: Our study demonstrates the critical role of ferroptosis in LUAD, and it is expected to supply a reference for the prognostic stratification of LUAD. Translational Medicine Ferroptosis prognostic signature lung adenocarcinoma TCGA Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Full Text Tables The tables are provided in the Supplementary Files section. Supplementary Files Supplementarymaterials.pdf table.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-49010","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":1109410,"identity":"02ae0aa4-8e15-4ad1-b5c8-559bf15820e5","order_by":0,"name":"Lei Sun","email":"","orcid":"","institution":"The First Affiliated Hospital of China Medical University, Shenyang 110001, China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Sun","suffix":""},{"id":1109411,"identity":"5a0dc9a4-405d-4db1-b93e-f5612cd47ec0","order_by":1,"name":"Jia Gu","email":"","orcid":"","institution":"The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Gu","suffix":""},{"id":1109412,"identity":"59071ff8-0450-44c1-96e7-1cce1083992d","order_by":2,"name":"Wenke Liu","email":"","orcid":"","institution":"The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wenke","middleName":"","lastName":"Liu","suffix":""},{"id":1109413,"identity":"d45b02e7-d996-4e4c-a72c-6c144a1b7377","order_by":3,"name":"Zhe Zhang","email":"","orcid":"","institution":"The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhe","middleName":"","lastName":"Zhang","suffix":""},{"id":1109414,"identity":"e59cad2e-4876-4877-a549-c318c6dd58d2","order_by":4,"name":"Yao Yao","email":"","orcid":"","institution":"The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yao","middleName":"","lastName":"Yao","suffix":""},{"id":1109415,"identity":"f432416c-15fe-4381-ae9f-ef8bf5e070c3","order_by":5,"name":"Tao Han","email":"","orcid":"","institution":"The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Han","suffix":""},{"id":1109416,"identity":"11a9c16f-4cc0-4179-9f3b-40dbb3c79b81","order_by":6,"name":"Wenya Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYFACxgYGxj82cvzsPWAuDx9RWg42pBlL9pxhYDgA1MJGlEUHGw4nbriRA9bCQFCLfPvhtscfdzAbS858e/Dxxxw7GTYG5oePbuDRYnAmsd3g4Bk2OX7pvGSDg9uSgQ5jMzbOwaeFIbFN4gAbj7Hk7BwziYPbmIFaeNik8WmR738I0iKRuOHmGZCWesJaGG4AbTnYZgD0Pg9Iy2HCWgxuAG05cyYBGMg5xgZntx3nYWMm4Bf5/vRnEhUV/4FRecbwQeW2ant+9uaHj/E6DBMwk6Z8FIyCUTAKRgEWAAC3Wktnx7kdxQAAAABJRU5ErkJggg==","orcid":"","institution":"The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Wenya","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2020-07-25 11:31:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-49010/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-49010/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":1771628,"identity":"13b07de6-5ef8-4c8f-9087-425b74151b9c","added_by":"auto","created_at":"2020-08-03 23:35:31","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":548835,"visible":true,"origin":"","legend":"The expression of ferroptosis-related genes between tumor tissues and paracancerous tissues. ** P \u003c 0.01 and *** P \u003c 0.001.","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-49010/v1/Figure1.jpg"},{"id":1771629,"identity":"64cf5abd-f934-4e3e-a3d0-6629c1cbcb79","added_by":"auto","created_at":"2020-08-03 23:35:31","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":488946,"visible":true,"origin":"","legend":"The six-mRNA signature can predict the overall survival rate of patients in the training set. (A) Survival curve between different risk groups. (B) ROC curve verifies the sensitivity and specificity of the prognostic signature. (C-D) Univariate and multivariate Cox regression analyses of the association between clinical features and overall survival of patients.","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-49010/v1/Figure2.jpg"},{"id":1771630,"identity":"ccec4b26-1d56-4ada-a35d-9eff417e26da","added_by":"auto","created_at":"2020-08-03 23:35:31","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":434976,"visible":true,"origin":"","legend":"Validation of the six‑mRNA signature in the test set. (A) Survival curve between different risk groups. (B) ROC curve verifies the sensitivity and specificity of the signature. (C-D) Univariate and multivariate Cox regression analyses of the association between clinical features and overall survival of patients.","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-49010/v1/Figure3.jpg"},{"id":1771631,"identity":"a004babd-6541-478c-9dcc-42847320324a","added_by":"auto","created_at":"2020-08-03 23:35:32","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":539058,"visible":true,"origin":"","legend":"The expression of ferroptosis-related IncRNAs and Construction of the seven‑IncRNA signature for predicting patient prognosis. (A-B) The expression of seven candidate ferroptosis-related IncRNAs between tumor tissues and paracancerous tissues. (C-D) Survival curve and ROC curve of the seven‑IncRNA signature. (E-F) Univariate and multivariate Cox regression analyses of the association between clinical features and overall survival of patients. *** P \u003c 0.001.","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-49010/v1/Figure4.jpg"},{"id":1771632,"identity":"58f785c3-85ec-41ad-bb28-06dc63889b20","added_by":"auto","created_at":"2020-08-03 23:35:32","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":426648,"visible":true,"origin":"","legend":"KEGG analysis of different signature groups in LUAD. (A) The KEGG analysis of the six‑mRNA signature. (B) The KEGG analysis of the seven‑IncRNA signature.","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-49010/v1/Figure5.jpg"},{"id":13520164,"identity":"95756351-ce47-4045-a9d0-cc6f7c4d02fa","added_by":"auto","created_at":"2021-09-17 00:26:24","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":627514,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-49010/v1_covered.pdf"},{"id":1771636,"identity":"b50bdb08-e7cc-4cf9-a519-c3ac780e4ec4","added_by":"auto","created_at":"2020-08-03 23:35:40","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":322394,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-49010/v1_stamped.pdf"},{"id":1771633,"identity":"912ccf64-4f0e-46b4-bded-f8c227e260c1","added_by":"auto","created_at":"2020-08-03 23:35:32","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":251019,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-49010/v1/Manuscript.pdf"},{"id":1771634,"identity":"a0864e98-9fed-4f6a-a57f-5aeb7b8ebc30","added_by":"auto","created_at":"2020-08-03 23:35:32","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":104550,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-49010/v1/Supplementarymaterials.pdf"},{"id":1771635,"identity":"2fb09a13-b6f3-4980-9bb3-2a7cdbb00bd7","added_by":"auto","created_at":"2020-08-03 23:35:32","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":85421,"visible":true,"origin":"","legend":"","description":"","filename":"table.pdf","url":"https://assets-eu.researchsquare.com/files/rs-49010/v1/table.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eLarge-Scale Transcriptome Analysis Identified Novel Ferroptosis-Related Gene Signatures for Predicting the Prognostic of Patients with Lung Adenocarcinoma\u003c/p\u003e","fulltext":[{"header":"Full Text","content":"\u003cp\u003eThis preprint is available for \u003ca href='/article/rs-49010/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e.\u003c/p\u003e"},{"header":"Tables","content":"\u003cp\u003eThe tables are provided in the Supplementary Files section.\u003c/p\u003e"}],"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":false,"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":"Ferroptosis, prognostic signature, lung adenocarcinoma, TCGA","lastPublishedDoi":"10.21203/rs.3.rs-49010/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-49010/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Lung cancer is the most common of all malignant tumors. Traditional tumor staging has general sensitivity and specificity in predicting patient prognosis. Ferroptosis is a novel form of non-apoptotic form of cell death promoted by lipid peroxidation. Ferroptosis may be involved in the malignant progression of tumors through the regulation of glutathione depletion or the P53 signaling pathway. However, there are fewer studies on the impact of ferroptosis on tumor prognosis.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We summarized 22 molecules that regulate ferroptosis. The transcriptome and corresponding clinical data were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The Wilcoxon test was utilized to analyze the expression of ferroptosis-related genes. We established risk score signatures, and all patients divided into two groups. Survival curves and multifactorial Cox regression analyses were performed to explore the prognostic value of ferroptosis on lung adenocarcinoma (LUAD).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e We found that most ferroptosis-related genes are specifically expressed in LUAD tissue. We established a six‑mRNA signature and a seven‑IncRNA signature. All the models showed high predictive performance (AUC: 0.66–0.8), and patients in the low-risk group had higher overall survival than those in the high-risk group (P\u0026lt;0.05). The risk score is an independent risk factor for predicting the prognosis of LUAD.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Our study demonstrates the critical role of ferroptosis in LUAD, and it is expected to supply a reference for the prognostic stratification of LUAD. \u003c/p\u003e","manuscriptTitle":"Large-Scale Transcriptome Analysis Identified Novel Ferroptosis-Related Gene Signatures for Predicting the Prognostic of Patients with Lung Adenocarcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-08-03 23:35:31","doi":"10.21203/rs.3.rs-49010/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":"dd69ade8-09f8-4a63-93c0-fe9a0a685148","owner":[],"postedDate":"August 3rd, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":235224,"name":"Translational Medicine"}],"tags":[],"updatedAt":"2020-08-11T23:01:08+00:00","versionOfRecord":[],"versionCreatedAt":"2020-08-03 23:35:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-49010","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-49010","identity":"rs-49010","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}