This is a preprint.
Ultrasensitive detection of circulating LINE-1 ORF1p as a specific multi-cancer biomarker
- PMID: 36747644
- PMCID: PMC9900799
- DOI: 10.1101/2023.01.25.525462
Ultrasensitive detection of circulating LINE-1 ORF1p as a specific multi-cancer biomarker
Update in
-
Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker.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.
Publication types
Grants and funding
LinkOut - more resources
Full Text Sources