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Supplementary Figure 26 from Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker

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posted on 2024-01-08, 15:20 authored by Martin S. Taylor, Connie Wu, Peter C. Fridy, Stephanie J. Zhang, Yasmeen Senussi, Justina C. Wolters, Tatiana Cajuso, Wen-Chih Cheng, John D. Heaps, Bryant D. Miller, Kei Mori, Limor Cohen, Hua Jiang, Kelly R. Molloy, Brian T. Chait, Michael G. Goggins, Irun Bhan, Joseph W. Franses, Xiaoyu Yang, Mary-Ellen Taplin, Xinan Wang, David C. Christiani, Bruce E. Johnson, Matthew Meyerson, Ravindra Uppaluri, Ann Marie Egloff, Elyssa N. Denault, Laura M. Spring, Tian-Li Wang, Ie-Ming Shih, Jennifer E. Fairman, Euihye Jung, Kshitij S. Arora, Osman H. Yilmaz, Sonia Cohen, Tatyana Sharova, Gary Chi, Bryanna L. Norden, Yuhui Song, Linda T. Nieman, Leontios Pappas, Aparna R. Parikh, Matthew R. Strickland, Ryan B. Corcoran, Tomas Mustelin, George Eng, Ömer H. Yilmaz, Ursula A. Matulonis, Andrew T. Chan, Steven J. Skates, Bo R. Rueda, Ronny Drapkin, Samuel J. Klempner, Vikram Deshpande, David T. Ting, Michael P. Rout, John LaCava, David R. Walt, Kathleen H. Burns

Calibration curve for the large-volume (500 µL) MOSAIC assay.

Funding

National Institutes of Health (NIH)

Break Through Cancer (BTC)

Friends For an Earlier Breast Cancer Test (Earlier.org)

Minnesota Ovarian Cancer Alliance (MOCA)

U.S. Department of Defense (DOD)

Canary Foundation

Gray Foundation

The Concord (MA) Detect Ovarian Cancer Early Fund

Good Ventures Foundation (Good Ventures)

Friends of Dana-Farber Cancer Institute

Dana-Farber Cancer Institute (DFCI)

Dana-Farber/Harvard Cancer Center (DF/HCC)

ACD-Biotechne

Robert L. Fine Cancer Research Foundation

Worldwide Cancer Research (WCR)

Robertson Therapeutic Development Fund

Nile Albright Research Foundation

Vincent Memorial Research Foundation

Stand Up To Cancer (SU2C)

History

ARTICLE ABSTRACT

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. 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, cost-effective tools in cancer detection and monitoring.See related commentary by Doucet and Cristofari, p. 2502.This article is featured in Selected Articles from This Issue, p. 2489