Circulating tumor cell enumeration for improved screening and disease detection of patients with colorectal cancer

Wen-Sy Tsai; Wei-Shan Hung; Tzu-Min Wang; Hsuan Liu; Chia-Yu Yang; Shao-Min Wu; Hsueh-Ling Hsu; Yu-Chiao Hsiao; Hui-Ju Tsai; Ching-Ping Tseng

doi:10.1016/j.bj.2020.09.006

Circulating tumor cell enumeration for improved screening and disease detection of patients with colorectal cancer

Biomed J. 2021 Dec;44(6 Suppl 2):S190-S200. doi: 10.1016/j.bj.2020.09.006. Epub 2020 Sep 30.

Authors

Affiliations

¹ Division of Colon and Rectal Surgery, Department of Surgery, Linko Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan.
² Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ Division of Colon and Rectal Surgery, Department of Surgery, Linko Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁴ Division of Colon and Rectal Surgery, Department of Surgery, Linko Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁵ Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁶ Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. Electronic address: ctseng@mail.cgu.edu.tw.

Abstract

Background: The immunochemical fecal occult blood test (iFOBT) for colorectal cancer (CRC) screening and the serum carcinoembryonic antigen (CEA) assay for disease detection of CRC is associated with a high false-positive rate and a low detection sensitivity, respectively. There is an unmet need to define additional modalities to complement these assays. Different subsets of circulating tumor cells (CTCs) are present in the peripheral blood of cancer patients. Whether or not CTCs testing supplements these clinical assays and is valuable for patients with CRC was investigated.

Methods: CTCs were enriched from pre-operative patients with CRC (n = 109) and the non-cancerous controls (n = 65). CTCs expressing either epithelial cell adhesion molecule (EpCAM) or podoplanin (PDPN, the marker associated with poor cancer prognosis) were defined by immunofluorescence staining and were analyzed alone or in combination with iFOBT or serum CEA.

Results: Patients with early or advanced stage of CRC can be clearly identified and differentiated from the non-cancerous controls (p < 0.001) by EpCAM⁺-CTC or PDPN⁺-CTC count. The sensitivity and specificity of EpCAM⁺-CTCs was 85.3% and 78.5%, respectively, when the cutoff value was 23 EpCAM⁺-CTCs/mL of blood; and the sensitivity and specificity of PDPN⁺-CTCs was 78.0% and 75.4%, respectively, when the cutoff value was 7 PDPN⁺-CTCs/mL of blood. Combined analysis of iFOBT with the EpCAM⁺-CTC and PDPN⁺-CTC count reduced the false-positive rate of iFOBT from 56.3% to 18.8% and 23.4%, respectively. Combined analysis of serum CEA with the EpCAM⁺-CTC and PDPN⁺-CTC count increased the disease detection rate from 30.3% to 89.9% and 86.2%, respectively.

Conclusion: CTC testing could supplement iFOBT to improve CRC screening and supplement serum CEA assay for better disease detection of patients with CRC.

Keywords: Carcinoembryonic antigen; Circulating tumor cells; Colorectal cancer; Epithelial cell adhesion molecule; Immunochemical fecal occult blood test; Podoplanin.

MeSH terms

Biomarkers, Tumor
Carcinoembryonic Antigen
Colorectal Neoplasms* / metabolism
Early Detection of Cancer
Epithelial Cell Adhesion Molecule
Humans
Neoplastic Cells, Circulating* / pathology

Substances

Biomarkers, Tumor
Carcinoembryonic Antigen
Epithelial Cell Adhesion Molecule