Carcinoembryonic antigen-positive circulating epithelial cells as a biomarker for the diagnosis and prognosis of colorectal cancer

Abstract

The serum carcinoembryonic antigen (CEA) level lacks the specificity required for precise colorectal cancer (CRC) diagnosis. To address this limitation, we investigated CEA-expressing circulating epithelial cells (CCECs) as a diagnostic biomarker for CRC. Human peripheral blood mononuclear cells, obtained from patient samples, were suspended in Matrigel and subjected to cyto-centrifugation for immunohistochemistry staining, enhancing cell immobilization on glass slides. Using this method, we successfully identified CCECs in 63% of CRC patients, whereas they were present in only 5% of non-cancer cohorts. Subsequently, receiver operating characteristic (ROC) analysis demonstrated the superior diagnostic capability of the CCEC count (area under the curve [AUC]-ROC: 0.817; p = 0.003) compared to serum CEA levels (AUC-ROC: 0.747; p = 0.021). Furthermore, a strong correlation emerged between tissue CEA expression and CCEC counts, with CCECs exclusively detectable in patients with CEA-positive tumors. The CCEC count also exhibited a high predictive value for estimating lymphovascular invasion and distant metastasis. To further enhance the clinical utility of CCECs, we established an integrated CEA score by combining serum CEA levels and CCEC counts. This scoring system exhibited superior AUC-ROCs for distinguishing malignancy and estimating tumor metastatic potential compared to individual biomarkers. Our study underscores the promise of CCECs as a biomarker for distinguishing and diagnosing CRC.