Single-cell transcriptomics reveals the landscape of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy and the potential resistance role of LGALS1

Single-cell transcriptomics reveals the landscape of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy and the potential resistance role of LGALS1 | 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 Article Single-cell transcriptomics reveals the landscape of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy and the potential resistance role of LGALS1 Qihang Yan, Wuguang Chang, Zhenguo Li, Wingshing Wong, Li Gong, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5264872/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 Neoadjuvant chemoradiotherapy (neoCRT) remodels the tumor microenvironment in esophageal squamous cell carcinoma (ESCC). This study aimed to analyze the impact of neoCRT on the immune landscape of ESCC and identify potential resistance genes using single-cell RNA-seq (scRNA-seq). Methods We obtained scRNA-seq datasets of ESCC from the GEO database and evaluated changes in the number and function of key T cells and myeloid cells following neoCRT. Malignant epithelial cells were analyzed using inferCNV and subjected to differential analysis to identify potential drug-resistance genes. The gene LGALS1, implicated in drug resistance, was further investigated. The effects of short hairpin RNA knockdown of LGALS1 on cisplatin sensitivity were assessed both in vitro and in vivo. Additionally, potential resistance pathways were explored through a protein-protein interaction network and gene set enrichment analysis. Results NeoCRT treatment resulted in the activation of T cells and myeloid cells within the tumor microenvironment, enhancing the anti-tumor immune response and improving tumor cell eradication compared to the surgery group. However, neoCRT simultaneously increased LGALS1 expression in tumor cells, which contributed to the development of drug resistance. Mechanistically, LGALS1 overexpression was associated with increased platinum resistance, enhanced DNA repair, resistance to apoptosis and epithelial-mesenchymal transition. Conclusion scRNA-seq analysis revealed that neoCRT significantly alters the immune landscape of ESCC. While neoCRT activates T cells and myeloid cells to target tumor cells effectively, it also induces LGALS1 overexpression, which contributes to drug resistance and potential relapse. Biological sciences/Cancer/Cancer therapy/Chemotherapy Health sciences/Oncology/Cancer/Gastrointestinal cancer/Oesophageal cancer scRNA-seq esophegeal squamous cell carcinoma LGALS1 tumor microenvironment resistance Full Text Additional Declarations No competing interests reported. Supplementary Files WBRepeat.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-5264872","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":380856954,"identity":"9b635079-baed-4b89-b4f2-2dd8fbc95fb8","order_by":0,"name":"Qihang Yan","email":"","orcid":"","institution":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Qihang","middleName":"","lastName":"Yan","suffix":""},{"id":380856955,"identity":"281e1b56-938d-4f55-9392-f4b574663860","order_by":1,"name":"Wuguang 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LGALS1","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":"scRNA-seq, esophegeal squamous cell carcinoma, LGALS1, tumor microenvironment, resistance","lastPublishedDoi":"10.21203/rs.3.rs-5264872/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5264872/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eNeoadjuvant chemoradiotherapy (neoCRT) remodels the tumor microenvironment in esophageal squamous cell carcinoma (ESCC). This study aimed to analyze the impact of neoCRT on the immune landscape of ESCC and identify potential resistance genes using single-cell RNA-seq (scRNA-seq).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe obtained scRNA-seq datasets of ESCC from the GEO database and evaluated changes in the number and function of key T cells and myeloid cells following neoCRT. Malignant epithelial cells were analyzed using inferCNV and subjected to differential analysis to identify potential drug-resistance genes. The gene LGALS1, implicated in drug resistance, was further investigated. The effects of short hairpin RNA knockdown of LGALS1 on cisplatin sensitivity were assessed both in vitro and in vivo. Additionally, potential resistance pathways were explored through a protein-protein interaction network and gene set enrichment analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eNeoCRT treatment resulted in the activation of T cells and myeloid cells within the tumor microenvironment, enhancing the anti-tumor immune response and improving tumor cell eradication compared to the surgery group. However, neoCRT simultaneously increased LGALS1 expression in tumor cells, which contributed to the development of drug resistance. Mechanistically, LGALS1 overexpression was associated with increased platinum resistance, enhanced DNA repair, resistance to apoptosis and epithelial-mesenchymal transition.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003escRNA-seq analysis revealed that neoCRT significantly alters the immune landscape of ESCC. While neoCRT activates T cells and myeloid cells to target tumor cells effectively, it also induces LGALS1 overexpression, which contributes to drug resistance and potential relapse.\u003c/p\u003e","manuscriptTitle":"Single-cell transcriptomics reveals the landscape of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy and the potential resistance role of LGALS1","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-25 16:39:17","doi":"10.21203/rs.3.rs-5264872/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":"78783d6a-c4b5-44d4-afe4-b094e17608fa","owner":[],"postedDate":"November 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":40559774,"name":"Biological sciences/Cancer/Cancer therapy/Chemotherapy"},{"id":40559775,"name":"Health sciences/Oncology/Cancer/Gastrointestinal cancer/Oesophageal cancer"}],"tags":[],"updatedAt":"2024-12-05T11:08:48+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-25 16:39:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5264872","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5264872","identity":"rs-5264872","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}