Open AccessClinical utility of CDH17 biomarker in tumor tissues and liquid biopsies for detection and prognostic staging of colorectal cancer (CRC).
Author(s) -
Helen Tsoi,
Kwong-Fai Wong,
John M. Luk,
Don Staunton
Publication year - 2019
Publication title -
journal of global oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.002
H-Index - 17
ISSN - 2378-9506
DOI - 10.1200/jgo.2019.5.suppl.53
Subject(s) - biomarker , cancer , immunohistochemistry , antibody , cancer research , medicine , antigen , colorectal cancer , tumor progression , monoclonal antibody , pathology , oncology , biology , immunology , biochemistry
53 Background: Cancer surveillance using blood-based biomarker tests allows for early cancer detection and more effective prompt treatment. Immunohistochemical staining of tumor-specific antigens can also provide valuable prognostic information and contribute to the design of treatment strategy. Our early studies and work from other investigators have identified cadherin-17 (CDH17) as a promising biomarker in both tumor tissues and liquid biopsies. CDH17 overexpression in cancer tissue was found predictive of poor prognosis in patients with gastric cancer, hepatocellular carcinoma and ovarian cancer. Plasma CDH17 was elevated in patients with gastric cancer when compared to healthy subjects. However, despite the diagnostic and prognostic value of CDH17, robust and accurate assays for CDH17 detection in liquid and tumor biopsies have yet to be developed. Methods: In order to establish CDH17 immunoassays, we have first generated a proprietary library of more than 300 antibodies against CDH17, and from this library, isolated a panel of monoclonal antibodies (mAbs) exhibiting specific and high-affinity binding to the different extracellular domains of CDH17. Results: The immunohistochemical staining of CRC tissues with one of our mAbs revealed a stepwise increase in CDH17 with the progression of cancer from early to late CRC. A sandwich-ELISA was also developed to show significantly elevated plasma CDH17 in patients with CRC when compared to healthy individuals. Like CDH17 expression in CRC tissues, plasma CDH17 also showed a gradual increase with progression to more advanced stages of CRC. The newly developed ELISA also demonstrated that the number of CDH17-containing exosomes was significantly higher in blood isolated from patients with CRC. Notably, our mAbs could also enumerate CDH17-positive circulating tumor cells (CTCs), of which the level was associated with tumor stage. Conclusions: All these findings clearly indicate the clinical utility of CDH17 in tumor tissues and liquid biopsies for detection and prognostic staging of CRC. Further validation of our proprietary CDH17 immunoassays are being conducted in multiple independent CRC cohorts.