Ultrasensitive detection of circulating LINE-1 ORF1p as a specific multi-cancer biomarker.

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.

Serial Profiling of SARS-CoV-2 Antigens and Antibodies in COVID-19 Patient Plasma

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worldwide. PCR tests are currently the gold standard for diagnosis of the current coronavirus disease (COVID-19) and serology tests are used to detect seroconversion in infected patients. However, there is a lack of quantitative and ultra-sensitive viral antigen tests for COVID-19. Here we show that Single Molecule Array (Simoa) assays can quantitatively detect SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens in the plasma of COVID-19 patients. Combined with Simoa anti-SARS-CoV-2 serological assays, we show correlation between production of antibodies and clearance of viral antigens from serial plasma samples from COVID-19 patients. Furthermore, we demonstrate the presence of viral antigens in blood correlates with disease severity in hospitalized COVID-19 patients. These data suggest that SARS-CoV-2 viral antigens in the blood could be a marker for severe COVID-19 cases. One Sentence SummarySARS-CoV-2 antigens S1, spike, and nucleocapsid and anti-SARS-Cov-2 antibodies were measured in longitudinal plasma samples from COVID-19 patients using Single Molecule Array (Simoa) assays.