Epitope Detection in Monocytes (EDIM) As a New Method of Liquid Biopsy in Pediatric Rhabdomyosarcoma

Abstract

Biomarkers allowing characterization of pediatric rhabdomyosarcoma (RMS) are lacking. Epitope detection in monocytes (EDIM) is a novel method focused on detection of the biomarkers TKTL1 (transketolase-like protein 1) and Apo10 (epitope of DNaseX) in activated monocytes (CD14+/CD16+) from patient’s blood. We investigated the expression of these biomarkers in RMS cell lines, tumor material, and peripheral blood from RMS patients. Expression levels of TKTL1 and DNaseX/Apo10 in RMS cell lines (RH30, RD) and tumor samples were analyzed by RT-PCR and flow cytometry. Blood samples of 29 RMS patients were measured and compared to 27 healthy individuals. The percentages of activated CD14+/CD16+ monocytes harboring TKTL1 and Apo10 were determined. EDIM-TKTL1 and EDIM-Apo10 expression scores were calculated. The relationship between TKTL1 expression and DNA-hypomethylation was evaluated. Both RMS cell lines and tumor samples showed significantly higher expression levels of TKTL1 and DNaseX/Apo10 compared to skeletal muscle cells (SkMC). EDIM-TKTL1 and EDIM-Apo10 scores were positive in 96.5% of patients with RMS. All healthy controls had negative corresponding scores. RMS cell lines show increased expression levels of the biomarkers TKTL1 and DNaseX/Apo10. The sensitivity of the EDIM blood test indicates that this assay might serve as an additional tool in pediatric RMS.

Case Report: Early detection of lung carcinoid in an asymptomatic individual by blood-test initiated PET-CT imaging

“…The PanTum Detect blood test is based on the unique technique of epitope detection in monocytes (EDIM) utilizing the fact that activated monocytes/macrophages (CD14+/CD16+), belonging to the group of circulating cancer-associated macrophage-like cells (CAMLs), phagocytose tumor cells and contain tumor proteins intracellularly (11)(12)(13)(14)(15). To prove internalization of tumor particles by CD14+/CD16+ monocytes, co-culture experiments were performed (16). These can be detected by flow cytometry from peripheral blood samples using specific antibodies.…”