Detection of Marker Associated with CTC in Colorectal Cancer in Mononuclear Cells of Patients with Benign Inflammatory Intestinal Diseases

SIMPLE SUMMARY: Colorectal carcinoma (CRC) is one of the most frequent cancers in western countries, and non-invasive methods for early detection are still needed. Circulating tumor cells (CTC) in blood of CRC patients have been proven as prognostic and predictive biomarker; however, the suitability of CTC-associated markers for early CRC detection and discrimination from benign diseases has not been analyzed. Thus, this study investigated whether CTC-associated markers can also be detected in the blood of patients with benign inflammatory intestinal disease (IID) or whether they are specific for malignancy. The detection rate of CK20 and DEFA5 clearly differed in diseased patients and healthy controls, while LAD1 and PLS3 was found in all samples but with clear qualitative differences in gene expression. No association between inflammation severity and CTC marker expression was found in IID patients. Finally, PLS3 was identified to be a suitable marker for differentiation between malignant and non-malignant intestinal diseases or healthy controls. ABSTRACT: Colorectal carcinoma (CRC) belongs to the most common tumor entities in western countries. Circulating tumor cells (CTC) in blood of CRC patients are a powerful prognostic and predictive biomarker. However, whether CTC-associated markers can also be used for early CRC detection and discrimination from benign diseases is not known. This study investigated the presence of CTC-associated markers CK20, PLS3, LAD1, and DEFA5 in blood of patients with benign inflammatory intestinal disease (IID) and their correlation with malignancy. The detection rate of CK20 and DEFA5 significantly differed between diseased patients and healthy controls. LAD1 and PLS3 were detected in all samples with clear differences in gene expression. DEFA5 expression was higher in CRC and IID patients compared to healthy donors, while CK20 and PLS3 were lower in CRC compared to IID patients or healthy controls. Overall, all CTC-associated markers were detectable in blood of IID patients, but not correlating with inflammation severity. Finally, PLS3 emerged as a suitable marker for differentiation between malignant and non-malignant intestinal diseases or healthy controls, however its suitability for early CRC detection needs to be further validated.