Abstract
Detection of circulating (CTC) or disseminated tumor cells (DTC) are correlated with negative prognosis in esophageal cancer (EC) patients. In this study, DTC- and CTC-associated markers CK20 and DEFA5 were determined by RT-PCR in EC patients and correlated with clinical parameters to determine their prognostic impact. The blood and bone marrow (BM) of 216 EC patients after tumor resection with or without neoadjuvant therapy and as control blood samples from 38 healthy donors and BM from 24 patients with non-malignant diseases were analyzed. Both markers were detected in blood and BM of EC patients and the control cohort. A cut-off value was determined to define marker positivity for correlation with clinical data. CK20 expression was detected in 47/206 blood samples and in 49/147 BM samples of EC patients. DEFA5 positivity was determined in 96/206 blood samples and 98/147 BM samples, not correlating with overall survival (OS). However, CK20 positivity in BM and DEFA5 negativity in blood were associated with reduced OS in EC patients without neoadjuvant therapy, while in patients with neoadjuvant therapy DEFA5 positivity in BM was associated with improved OS. Overall, our study suggests DEFA5 as a prognostic biomarker in liquid biopsies of EC patients which requires further validation.
Highlights
According to global cancer statistics, esophageal cancer (EC) represents the sixth highest cause of cancer-related deaths with an ever-increasing incidence [1,2]
Atlas (https://www.proteinatlas.org/) [41], and RNAsequencing data in the Cancer Genome Atlas (TCGA) database indicate that the expression of either gene is not altered in EC compared to the normal tissue [42], CK20 was chosen as a biomarker for EC cells, because it has already been proven as a good indicator for circulating tumor cells (CTC)
To the best of our knowledge, our work is the first to investigate the prognostic value of CK20 and DEFA5 expression in liquid biopsies of a large cohort of 216 EC patients
Summary
According to global cancer statistics, esophageal cancer (EC) represents the sixth highest cause of cancer-related deaths with an ever-increasing incidence [1,2]. Despite the ongoing development of diagnostic measures such as endoscopy, computed tomography (CT), and positron emission tomography (PET), more than 60% of EC patients are diagnosed at an advanced tumor stage. This can be explained by the lack of symptoms in the early stage of the disease [6]. Clinical data show that in around 50% of patients, who were operated and showed no evidence of local or distant metastasis, a progression of disease occurred within 12 months after surgery [7] This is thought to be due to a clinically undetectable so-called minimal residual disease (MRD), which may be circulating tumor cells (CTC) or disseminated tumor cells (DTC) [8]. Both entities of tumor cells can originate from the same primary tumor and can be detected either in the blood as CTC or in the bone marrow and other secondary sites such as the liver or lung as DTC [9,10]
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