Biomarkers Apo10 and TKTL1: Epitope-detection in monocytes (EDIM) as a new diagnostic approach for cholangiocellular, pancreatic and colorectal carcinoma

Abstract

OBJECTIVE: The EDIM (Epitope detection in monocytes) blood test is based on two biomarkers Apo10 and TKTL1. Apo10 is responsible for cell proliferation and resistance to apoptosis. TKTL1 plays a major role in anaerobic glycolysis of tumor cells, leading to destruction of the basal membrane and metastasis as well as in controlling cell cycle. For the first time we analyzed Apo10 and TKLT1 in patients with cholangiocellular (CCC), pancreatic (PC), and colorectal carcinoma (CRC). METHODS: Blood samples of 62 patients with CCC, PC, and CRC were measured and compared to 29 control patients. We also investigated 13 patients with inflammatory conditions, because elevated TKTL1 and Apo10 have been previously described in affected individuals. Flow cytometry was used to detect surface antigens CD14 + /CD16 + (activated monocytes/macrophages). Percentages of macrophages harboring TKTL1 and Apo10 were determined. A combined EDIM score (EDIM-CS: TKTL1 plus Apo10) was calculated. Results were correlated with serum tumor markers CEA and CA19-9. RESULTS: Patients with CCC had 100% positive EDIM-CS but CEA and CA19-9 were positive in only 22.2% and 70%, respectively. Patients with PC had 100% positive EDIM-CS but positive tumor markers in only 37.5% (CEA) and 72.7% (CA19-9). Patients with CRC had 100% positive EDIM-CS but only 50% positive CEA. EDIM-CS was positive in 100% (62/62) of all cancer patients and in 0% of healthy individuals. Of the individuals with inflammation, 7.7% had a positive EDIM-CS. CONCLUSION: The sensitivity of the EDIM blood test and the comparison with traditional tumor markers indicate that this new test might improve the detection of carcinomas (CCC, PC and, CRC) and might be relevant for the diagnosis of all tumor entities.

TKTL1 as a Prognostic Marker in Pancreatic Ductal Adenocarcinoma and Its Correlation with FDG-PET-CT

“…In a previous study, TKTL1 could be detected using the epitope detection in monocytes (EDIM) blood test in all 34 pancreatic cancer patients studied, whereas a healthy control group exhibited a negative EDIM TKTL1 score [30]. Circulating TKTL1 is, however, not specific to pancreatic cancer, but also accompanies colorectal and biliary cancer.…”

Circulating Cells with Macrophage-like Characteristics in Cancer: The Importance of Circulating Neoplastic-Immune Hybrid Cells in Cancer

“…Like CTCs, CAMLs are detectable in patients with advanced cancers, but have low sensitivity for detecting disease in early stages [ 82 , 84 ]. Similarly, epitope-detection in monocyte (EDIM) technologies measure circulating CD14 + /CD16 + activated monocytes/macrophages with internalized tumor-derived proteins such as Apo10 and transketolase-like protein 1 (TKTL1) [ 88 , 89 ]. Such circulating cells are highly prevalent in oral cancer, PDAC, CRC, and cholangiocarcinoma, and reflect Apo10 and TKTL1 expression in primary tumors [ 88 , 89 ].…”

“…Similarly, epitope-detection in monocyte (EDIM) technologies measure circulating CD14 + /CD16 + activated monocytes/macrophages with internalized tumor-derived proteins such as Apo10 and transketolase-like protein 1 (TKTL1) [ 88 , 89 ]. Such circulating cells are highly prevalent in oral cancer, PDAC, CRC, and cholangiocarcinoma, and reflect Apo10 and TKTL1 expression in primary tumors [ 88 , 89 ]. Due to definitional and measurement differences, it is difficult to assess whether cells detected by EDIM platforms are CAMLs, as phagocytosis is just one method by which circulating cells in cancer can reflect tumor characteristics, such as cell death associated with treatment response.…”

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

“…These monocytes phagocytize tumor cells and store tumor proteins intracellularly. They can be detected in samples from peripheral blood of the patients using specific antibodies [ 12 ]. Particularly, the EDIM blood test focuses on the detection of two biomarkers, TKTL1 (transketolase-like protein 1) and Apo10 (epitope of DNaseX overexpressed in cancer cells), in CD14 + /CD16 + activated monocytes [ 12 ].…”

“…It has been shown that Apo10 is highly expressed in neoplastic cells, including in carcinomas, sarcomas, glioblastomas, lymphomas, and leukemias [ 7 , 10 ]. In contrast, absent or only weak expression has been observed in hematopoietic cells [ 12 , 23 ].…”