Opposing Kinase Signaling May Underlie the Inverse Relationship Between Cancer and Alzheimer’s Disease

Opposing Kinase Signaling May Underlie the Inverse Relationship Between Cancer and Alzheimer’s Disease | 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 Opposing Kinase Signaling May Underlie the Inverse Relationship Between Cancer and Alzheimer’s Disease Joyce Fang, Xinkun Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9655426/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 Cancer and Alzheimer’s disease cause millions of deaths worldwide each year. Epidemiological studies report an inverse relationship between these diseases, where Alzheimer’s disease patients have reduced cancer risk and vice versa. However, the molecular basis of this relationship remains poorly understood. In this study, we reanalyzed previously published proteomic and phosphoproteomic datasets to investigate this relationship. Differentially abundant proteins were identified in lung cancer and glioblastoma samples relative to normal controls and compared with proteins altered in Alzheimer’s disease brains, revealing 37 proteins with opposing abundance patterns. Protein–protein interaction and pathway enrichment analyses revealed enrichment in kinase signaling and phosphorylation pathways. Phosphoproteomic analysis identified 69 differentially phosphorylated sites with opposing patterns between cancer and Alzheimer’s disease. Kinase–substrate enrichment analysis identified 24 kinases with opposing activity profiles. Integration of kinase activity and phosphosite data identified 16 kinase–phosphosite pairs, including 5 high-confidence pairs with opposing patterns and functional relevance to both diseases. Together, these findings highlight opposing kinase signaling as a key feature of the inverse relationship and suggest potential biomarkers and therapeutic targets. This study provides a novel systems-level framework for investigating inverse disease relationships, supported by an interactive R Shiny application for data exploration (https://advscancer.shinyapps.io/advscancer/) Bioinformatics proteomics phosphoproteomics kinase signaling Alzheimer’s disease cancer inverse disease relationship kinase–substrate enrichment analysis Full Text Additional Declarations The authors declare no competing interests. Supplementary Files supplementarydata.xlsx readme.txt 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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Epidemiological studies report an inverse relationship between these diseases, where Alzheimer’s disease patients have reduced cancer risk and vice versa. However, the molecular basis of this relationship remains poorly understood.\u003c/p\u003e\n\u003cp\u003eIn this study, we reanalyzed previously published proteomic and phosphoproteomic datasets to investigate this relationship. Differentially abundant proteins were identified in lung cancer and glioblastoma samples relative to normal controls and compared with proteins altered in Alzheimer’s disease brains, revealing 37 proteins with opposing abundance patterns. Protein–protein interaction and pathway enrichment analyses revealed enrichment in kinase signaling and phosphorylation pathways.\u003c/p\u003e\n\u003cp\u003ePhosphoproteomic analysis identified 69 differentially phosphorylated sites with opposing patterns between cancer and Alzheimer’s disease. Kinase–substrate enrichment analysis identified 24 kinases with opposing activity profiles. Integration of kinase activity and phosphosite data identified 16 kinase–phosphosite pairs, including 5 high-confidence pairs with opposing patterns and functional relevance to both diseases.\u003c/p\u003e\n\u003cp\u003eTogether, these findings highlight opposing kinase signaling as a key feature of the inverse relationship and suggest potential biomarkers and therapeutic targets. 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