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Four plasma methods were evaluated: the SignaL machine-learning cfDNA fragmentation algorithm, a Protein-17 assay for 17 cancer-associated proteins, a global aneuploidy score (GAS), and cfDNA mutation analysis of 15 frequently mutated colorectal cancer genes. Using 99.5% specificity thresholds, SignaL detected 9/40 AA at 100% specificity, Protein-17 detected 5/40 AA at 100% specificity, GAS detected 11/40 AA with 93.8% specificity, and combined methods detected 16/40 AA.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-blood-based-assay-for-detection-of-patients-with-advanced-adenomas/373180/",{"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/a-blood-based-assay-for-detection-of-patients-with-advanced-adenomas/373180.png","ImageObject",300,407,{"name":92,"@type":93},"Margaret","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-23",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 goal of the blood-based assay study?","Question",{"text":112,"@type":113},"To detect patients with advanced adenomas using plasma-based tests, supporting more effective colorectal cancer prevention.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which four plasma detection methods were evaluated?",{"text":117,"@type":113},"SignaL based on cfDNA fragmentation, a Protein-17 assay measuring 17 cancer-associated proteins, a global aneuploidy score (GAS), and cfDNA mutation analysis of 15 colorectal cancer genes.",{"name":119,"@type":110,"acceptedAnswer":120},"How did the combined approach perform compared with single methods?",{"text":121,"@type":113},"At 99.5% specificity thresholds, combining SignaL, the Protein-17 assay, and GAS detected 16/40 AAs (40%) with 93.8% specificity.","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},373180,1790616056,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"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},137451207643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","RESEARCH ARTICLE  [https://doi.org/10.1158/2767-9764.CRC-24-0398](https://doi.org/10.1158/2767-9764.CRC-24-0398)  OPEN ACCESS  \nA Blood-Based Assay for Detection of Patients with Advanced Adenomas  \nKamel Lahouel1,2,3, Christopher Douville4, Brenda Diergaarde5, Joshua D. Cohen4, Haley Grant6, Albert Kuo6, Saad K. Ansari3,7, Yuxuan Wang4, Anne Marie O’Broin-Lennon4, Maria Popoli4, Janine Ptak4, Natalie Silliman4, Lisa Dobbyn4, Nadine Nehme4, Jeanne Tie8, Peter Gibbs8, Nickolas Papadopoulos4, Kenneth W. Kinzler4, Bert Vogelstein4, Robert E. Schoen9,10, and Cristian Tomasetti1,2,3,6  \n􀀶  \nABSTRACT  \nScreening for colorectal cancer with blood-based testing should detect advanced adenomas (AA), facilitating more effective cancer prevention. We evaluated four different methods to detect AAs in plasma: (i) a machine learning algorithm, Signatures of fragment Length (SignaL), based on cell-free DNA (cfDNA) fragmentation; (ii) a “Protein-17” assay measuring 17 cancer-associated proteins; (iii) a global aneuploidy score (GAS); and (iv) cfDNA mutation analysis querying 15 genes commonly mutated in colorectal cancer. Existing data from study populations with and without cancer were utilized to determine 99.5% specificity thresholds. We studied 40 AA cases and 32 colonoscopy-negative controls. SignaL detected 9/40 AAs [22.5%, 95% confidence interval (CI), 12.3%– 37.5%] at 100% specificity (95% CI, 89.3%–100%) . Protein-17 detected 5/  \n40 AAs (12.5%, 95% CI, 5.5%–26.1%) including three cases not identified by SignaL, at 100% specificity (95% CI, 89.3%–100%) . GAS detected 11/  \n40 AAs (27.5%, 95% CI, 16.1%–42.8%) but resulted in 2/32 positive controls (93.8% specificity, 95% CI, 79.9%–98.3%) . Combining SignaL,  \nthe Protein-17 assay, and GAS at the 99.5% specificity thresholds resulted in detection of 16/40 AAs (40%, 95% CI, 26.3%–55.4%) at 93.8% specificity (95% CI, 79.9%–98.3%) . Of 32/40 evaluable AA plasma samples, only one was cfDNA mutation positive at level of significance of 0.01. A blood-based assay based on the analysis of repeated sequence elements plus proteins seems to be able to detect a considerable fraction of patients with AA at relatively high specificity. Large, prospective studies are required to determine whether this approach can add to the options currently available for screening patients for premalignant lesions of the colon.  \nSignificance: Blood-based screening for colorectal cancer could improve testing uptake and outcomes. We propose novel methods to detect AAsin plasma using cfDNA fragmentation patterns, cancer-associated proteins, and aneuploidy with high specificity. Larger studies are needed to validate clinical utility.  \n1Center for Cancer Prevention and Early Detection, City of Hope, Duarte, California. 2Division of Mathematics for Cancer Evolution and Early Detection, Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, California. 3Division of Integrated Cancer Genomics, Translational Genomics Research Institute, Phoenix, Arizona. 4Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, Maryland. 5Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania. 6Department of Biostatistics, Johns Hopkins University School of Public Health, Baltimore, Maryland. 7Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, Maryland. 8Division of Personalized Oncology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. 9Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. 10Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.  \nK. Lahouel, C. Douville, and B. Diergaarde contributed equally to this article. Corresponding Authors: Kamel Lahouel, The Translational Genomics Research Institute, 445 N 5th St, Phoenix, AZ 85004. E-mail: [klahoue","cbCaidGYo7gGXPLo","https://ap.wps.com/l/cbCaidGYo7gGXPLo","pdf",6174617,11,"English","# Abstract\n## Methods and evaluated assays\n## Results and detection performance\n## Significance","[{\"question\":\"What is the main goal of the blood-based assay study?\",\"answer\":\"To detect patients with advanced adenomas using plasma-based tests, supporting more effective colorectal cancer prevention.\"},{\"question\":\"Which four plasma detection methods were evaluated?\",\"answer\":\"SignaL based on cfDNA fragmentation, a Protein-17 assay measuring 17 cancer-associated proteins, a global aneuploidy score (GAS), and cfDNA mutation analysis of 15 colorectal cancer genes.\"},{\"question\":\"How did the combined approach perform compared with single methods?\",\"answer\":\"At 99.5% specificity thresholds, combining SignaL, the Protein-17 assay, and GAS detected 16/40 AAs (40%) with 93.8% specificity.\"}]","A Blood-Based Assay for Detection of Patients with Advanced Adenomas | PDF",1790197489,28]