Detection of Circulating and Disseminated Tumor Cells and Their Prognostic Value under the Influence of Neoadjuvant Therapy in Esophageal Cancer Patients

CANCERS(2022)

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摘要
Simple Summary Esophageal cancer (EC) has a poor prognosis and a high mortality rate. This study investigated the expression of CK20 and DEFA5, markers being associated with circulating (CTC) and disseminated tumor cells (DTC), in blood and bone marrow (BM) of EC patients, and correlated positivity rates with clinical data to assess the prognostic impact. Both markers were detected in blood and BM of EC patients and the control cohort so that a cut-off value was determined to define marker positivity for correlation with clinical parameters. CK20 and DEFA5 positivity in liquid biopsies of EC patients did not correlate with overall survival (OS). However, CK20 positivity in BM and DEFA5 negativity in blood were associated with reduced OS in patients without neoadjuvant therapy. In patients with neoadjuvant therapy, DEFA5 positivity in BM was associated with improved OS, pointing to the potential of DEFA5 as a prognostic biomarker in liquid biopsies of EC patients. 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.
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关键词
liquid biopsy, esophageal carcinoma, CTC, DTC, CK20, DEFA5
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