Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker
| Title: | Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker |
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| Authors: | Taylor, Martin S.; Wu, Connie; Fridy, Peter C.; Zhang, Stephanie J.; Senussi, Yasmeen; Wolters, Justina C.; Cajuso, Tatiana; Cheng, Wen Chih; Heaps, John D.; Miller, Bryant D.; Mori, Kei; Cohen, Limor; Jiang, Hua; Molloy, Kelly R.; Chait, Brian T.; Goggins, Michael G.; Bhan, Irun; Franses, Joseph W.; Yang, Xiaoyu; Taplin, Mary Ellen; Wang, Xinan; Christiani, David C.; Johnson, Bruce E.; Meyerson, Matthew; Uppaluri, Ravindra; Egloff, Ann Marie; Denault, Elyssa N.; Spring, Laura M.; Wang, Tian Li; Shih, Ie Ming; Fairman, Jennifer E.; Jung, Euihye; Arora, Kshitij S.; Yilmaz, Osman H.; Cohen, Sonia; Sharova, Tatyana; Chi, Gary; Norden, Bryanna L.; Song, Yuhui; Nieman, Linda T.; Pappas, Leontios; Parikh, Aparna R.; Strickland, Matthew R.; Corcoran, Ryan B.; Mustelin, Tomas; Eng, George; Yilmaz, Ömer H.; Matulonis, Ursula A.; Chan, Andrew T.; Skates, Steven J.; Rueda, Bo R.; Drapkin, Ronny; Klempner, Samuel J.; Deshpande, Vikram; Ting, David T.; Rout, Michael P.; Lacava, John; Walt, David R.; Burns, Kathleen H. |
| Source: | Taylor, M S, Wu, C, Fridy, P C, Zhang, S J, Senussi, Y, Wolters, J C, Cajuso, T, Cheng, W C, Heaps, J D, Miller, B D, Mori, K, Cohen, L, Jiang, H, Molloy, K R, Chait, B T, Goggins, M G, Bhan, I, Franses, J W, Yang, X, Taplin, M E, Wang, X, Christiani, D C, Johnson, B E, Meyerson, M, Uppaluri, R, Egloff, A M, Denault, E N, Spring, L M, Wang, T L, Shih, I M, Fairman, J E, Jung, E, Arora, K S, Yilmaz, O H, Cohen, S, Sharova, T, Chi, G, Norden, B L, .... |
| Publication Year: | 2023 |
| Collection: | University of Groningen research database |
| Description: | Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring treatment response. Although proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity for these applications. Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is a transposable element protein overexpressed in carcinomas and high-risk precursors during carcinogenesis with negligible expression in normal tissues, suggesting ORF1p could be a highly specific cancer biomarker. To explore ORF1p as a blood-based biomarker, we engineered ultrasensitive digital immunoassays that detect mid-attomolar (10 −17 mol/L) ORF1p concentrations in plasma across multiple cancers with high specificity. Plasma ORF1p shows promise for early detection of ovarian cancer, improves diagnostic performance in a multianalyte panel, provides early therapeutic response monitoring in gastroesophageal cancers, and is prognostic for overall survival in gastroesophageal and colorectal cancers. Together, these observations nominate ORF1p as a multicancer biomarker with potential utility for disease detection and monitoring. SIGNIFICANCE: The LINE-1 ORF1p transposon protein is pervasively expressed in many cancers and is a highly specific biomarker of multiple common, lethal carcinomas and their high-risk precursors in tissue and blood. Ultrasensitive ORF1p assays from as little as 25 μL plasma are novel, rapid, costeffective tools in cancer detection and monitoring. |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 2159-8274; 2159-8290 |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37698949; info:eu-repo/semantics/altIdentifier/hdl/https://hdl.handle.net/11370/abae16a3-f9cf-4c41-958e-57c49e27d84c; info:eu-repo/semantics/altIdentifier/pissn/2159-8274; info:eu-repo/semantics/altIdentifier/eissn/2159-8290 |
| DOI: | 10.1158/2159-8290.CD-23-0313 |
| Availability: | https://hdl.handle.net/11370/abae16a3-f9cf-4c41-958e-57c49e27d84c; https://research.rug.nl/en/publications/abae16a3-f9cf-4c41-958e-57c49e27d84c; https://doi.org/10.1158/2159-8290.CD-23-0313; https://pure.rug.nl/ws/files/896649208/2532.pdf; https://www.scopus.com/pages/publications/85177463805 |
| Rights: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: | edsbas.929CFD68 |
| Database: | BASE |