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This work applies a systems approach to define molecular links between AST and cancer prognosis, metabolism, and immune signatures across transcriptomic and proteomic layers. Public expression and protein-interaction resources are integrated to test associations with pan-cancer subtypes, immune infiltration, and regulatory interactomes.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/pan-cancer-molecular-signatures-connecting-aspartate-transaminase-ast-to-cancer-prognosis-study-overview/330248/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/pan-cancer-molecular-signatures-connecting-aspartate-transaminase-ast-to-cancer-prognosis-study-overview/330248.png","ImageObject",300,407,{"name":92,"@type":93},"Finn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main clinical relevance of serum aspartate transaminase (sAST)?","Question",{"text":112,"@type":113},"sAST levels are commonly measured in clinical laboratories to assess liver health and disease, and evidence indicates prognostic value for several cancers beyond liver damage.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the study investigate connections between AST and cancer?",{"text":117,"@type":113},"The authors used a systems approach integrating public gene expression data (GTEx and TCGA) and protein-protein interaction networks to relate AST isoenzyme expression and interactomes to prognosis, metabolic features, and immune signatures.",{"name":119,"@type":110,"acceptedAnswer":120},"What did the results show about AST isoforms and cancer subtypes?",{"text":121,"@type":113},"AST transcript isoforms (GOT1 and GOT2) are expressed across many normal tissues; they are upregulated in several tumor types and downregulated in others, and AST is associated with pan-cancer molecular subtypes enriched for specific metabolic and immune signatures.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},330248,1790216896,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","bioRxiv preprint doi: [https://doi.org/10.1101/2024.03.01.582939](https://doi.org/10.1101/2024.03.01.582939); this version posted March 4, 2024. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC-ND 4.0 International license.  \nPan-cancer molecular signatures connecting aspartate transaminase (AST) to cancer prognosis, metabolic and immune signatures  \nGeoffrey H. Siwo*, Amit G. Singal, Akbar K. Waljee  \nDepartment of Learning Health Sciences, University of Michigan Medical School, Ann Arbor, MI, USA Department of Internal Medicine, UT Southwestern Medical Center, Dallas TX  \nCenter for Global Health Equity, University of Michigan, Ann Arbor, MI, USA  \n*Corresponding Author: [siwog@med.umich.edu](siwog@med.umich.edu)  \nbioRxiv preprint doi: [https://doi.org/10.1101/2024.03.01.582939](https://doi.org/10.1101/2024.03.01.582939); this version posted March 4, 2024. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC-ND 4.0 International license.  \n1 Abstract 2  \n3 Background  \n4 Serum aspartate transaminase (sAST) level is used routinely in conjunction with other clinical  \n5 assays to assess liver health and disease. Increasing evidence suggests that sAST is  \n6 associated with all-cause mortality and has prognostic value in several cancers, including  \n7 gastrointestinal and urothelial cancers. Here, we undertake a systems approach to unravel  \n8 molecular connections between AST and cancer prognosis, metabolism, and immune  \n9 signatures at the transcriptomic and proteomic levels.  \n10  \n11 Methods  \n12 We mined public gene expression data across multiple normal and cancerous tissues using the  \n13 Genotype Tissue Expression (GTEX) resource and The Cancer Genome Atlas (TCGA) to  \n14 assess the expression of genes encoding AST isoenzymes (GOT1 and GOT2) and their  \n15 association with disease prognosis and immune infiltration signatures across multiple tumors.  \n16 We examined the associations between AST and previously reported pan-cancer molecular  \n17 subtypes characterized by distinct metabolic and immune signatures. We analyzed human  \n18 protein-protein interaction networks for interactions between GOT1 and GOT2 with cancer- 19 associated proteins. Using public databases and protein-protein interaction networks, we  \n20 determined whether the subset of proteins that interact with AST (GOT1 and GOT2  \n21 interactomes) are enriched with proteins associated with specific diseases, miRNAs and  \n22 transcription factors.  \n23  \n24 Results  \n25 We show that AST transcript isoforms (GOT1 and GOT2) are expressed across a wide range of  \n26 normal tissues. AST isoforms are upregulated in tumors of the breast, lung, uterus, and thymus  \n27 relative to normal tissues but downregulated in tumors of the liver, colon, brain, kidney and  \n28 skeletal sarcomas. At the proteomic level, we find that the expression of AST is associated with  \n29 distinct pan-cancer molecular subtypes with an enrichment of specific metabolic and immune  \n30 signatures. Based on human protein-protein interaction data, AST physically interacts with  \n31 multiple proteins involved in tumor initiation, suppression, progression, and treatment. We find  \n32 enrichments in the AST interactomes for proteins associated with liver and lung cancer and  \n33 dermatologic diseases. At the regulatory level, the GOT1 interactome is enriched with the  \n34 targets of cancer-associated miRNAs, specifically mir34a – a promising cancer therapeutic,  \nbioRxiv preprint doi: [https://doi.org/10.1101/2024.03.01.582939](https://doi.org/10.1101/2024.03.01.582939); this version posted March 4, 2024. The copyright holder for this preprint (which was not certified by pe","cbCaibipeYJVTKmB","https://ap.wps.com/l/cbCaibipeYJVTKmB","pdf",1495776,43,"English","# Abstract\n# Background\n# Methods\n# Results\n# Conclusions\n# Introduction","[{\"question\":\"What is the main clinical relevance of serum aspartate transaminase (sAST)?\",\"answer\":\"sAST levels are commonly measured in clinical laboratories to assess liver health and disease, and evidence indicates prognostic value for several cancers beyond liver damage.\"},{\"question\":\"How did the study investigate connections between AST and cancer?\",\"answer\":\"The authors used a systems approach integrating public gene expression data (GTEx and TCGA) and protein-protein interaction networks to relate AST isoenzyme expression and interactomes to prognosis, metabolic features, and immune signatures.\"},{\"question\":\"What did the results show about AST isoforms and cancer subtypes?\",\"answer\":\"AST transcript isoforms (GOT1 and GOT2) are expressed across many normal tissues; they are upregulated in several tumor types and downregulated in others, and AST is associated with pan-cancer molecular subtypes enriched for specific metabolic and immune signatures.\"}]","Pan-cancer molecular signatures connecting aspartate transaminase (AST) to cancer prognosis - Study overview | PDF",1789987881,108]