Co-expression and prognostic significance of putative CSC markers CD44, CD133, wild-type EGFR and EGFRvIII in metastatic colorectal cancer
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Said Abdullah Khelwatty1, Sharadah Essapen1,2, Izhar Bagwan3, Margaret Green3, Alan M. Seddon1 and Helmout Modjtahedi1
1School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston, UK
2St. Luke’s Cancer Centre, Royal Surrey County Hospital, Guildford, Surrey, UK
3Department of Histopathology, Royal Surrey County Hospital, Guildford, Surrey, UK
Helmout Modjtahedi, email: [email protected]
Keywords: CSC; colorectal cancer; EGFR; immunohistochemistry
Received: January 15, 2019 Accepted: February 15, 2019 Published: March 01, 2019
The presence of colorectal cancer stem cells (CSCs) have been associated with tumour initiation and resistance to therapy. This study investigated the co-expression and prognostic significance of the CSCs biomarkers CD44 and CD133 with wild-type EGFR (wtEGFR) and EGFRvIII in colorectal cancer (CRC). The expression of these biomarkers were determined in tumours from 70 patients with metastatic CRC by immunohistochemistry, and in a panel of human CRC cell lines, and their variants with acquired-resistance to EGFR inhibitors, by flow cytometry. The expression of CD44, CD133, wtEGFR and EGFRvIII were present in 17%, 23%, 26% and 13% of cases and the co-expression of CD44/CD133 with wtEGFR and EGFRvIII were present in 9% and 3% of the cases respectively. Only co-expression of CSCs/EGFRvIII (P = 0.037), and amphiregulin (P = 0.017) were associated with worse overall survival. Interestingly, disease-free survival was improved in BTC expressing patients (P = 0.025). In vitro CD133 expression and its co-expression with CD44 were associated with primary-resistance to irinotecan and acquired-resistance to anti-EGFR inhibitors respectively. Our results suggest co-expression of CSCs and EGFRvIII could be potential biomarkers of worse overall survival and resistance to therapy in patients with mCRC and warrants further validation in a larger cohort.
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