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  • Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker.
    Taylor MS, Wu C, Fridy PC, Zhang SJ, Senussi Y, Wolters JC, Cajuso T, Cheng WC, Heaps JD, Miller BD, Mori K, Cohen L, Jiang H, Molloy KR, Chait BT, Goggins MG, Bhan I, Franses JW, Yang X, Taplin ME, Wang X, Christiani DC, Johnson BE, Meyerson M, Uppaluri R, Egloff AM, Denault EN, Spring LM, Wang TL, Shih IM, Fairman JE, Jung E, Arora KS, Yilmaz OH, Cohen S, Sharova T, Chi G, Norden BL, Song Y, Nieman LT, Pappas L, Parikh AR, Strickland MR, Corcoran RB, Mustelin T, Eng G, Yilmaz ÖH, Matulonis UA, Chan AT, Skates SJ, Rueda BR, Drapkin R, Klempner SJ, Deshpande V, Ting DT, Rout MP, LaCava J, Walt DR, Burns KH. Taylor MS, et al. Cancer Discov. 2023 Dec 12;13(12):2532-2547. doi: 10.1158/2159-8290.CD-23-0313. Cancer Discov. 2023. PMID: 37698949 Free PMC article.

Abstract

Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring treatment response. While proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity for these applications. Long INterspersed Element-1 (LINE-1, L1) open reading frame 1 protein (ORF1p) is a transposable element protein overexpressed in carcinomas and high-risk precursors during carcinogenesis with negligible detectable expression in corresponding normal tissues, suggesting ORF1p could be a highly specific cancer biomarker. To explore the potential of ORF1p as a blood-based biomarker, we engineered ultrasensitive digital immunoassays that detect mid-attomolar (10-17 M) ORF1p concentrations in patient plasma samples across multiple cancers with high specificity. Plasma ORF1p shows promise for early detection of ovarian cancer, improves diagnostic performance in a multi-analyte panel, and provides early therapeutic response monitoring in gastric and esophageal cancers. Together, these observations nominate ORF1p as a multi-cancer biomarker with potential utility for disease detection and monitoring.

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