Evaluation of plasma total and cleaved cytokeratin 18 as predictive markers of chemotherapy in colorectal cancer
e15091 Background: Cytokeratin 18 (CK18) is a cytoskeletal protein present in the circulation of cancer patients. Caspase-cleaved CK18 fragments are released from apoptotic cells and may be a simple non-invasive tool for measuring response to chemotherapy. This study aims to assess the associations between levels of CK18 with clinical parameters in patients with metastatic colorectal cancer (mCRC) receiving palliative chemotherapy. Methods: Prospectively collected plasma from 23 mCRC patients were analysed for the presence of total CK18 (M65, Peviva) and cleaved CK18 (M30-Apoptosense, Peviva) using an ELISA assay. 8 patients received 2nd-line chemotherapy (irinotecan) and 15 patients received 1st-line 5FU-based chemotherapy. Levels of both total and cleaved CK18 were determined at day 0 prior to chemotherapy and +24 hours for 2nd-line patients or +72 hours for 1st-line patients post-chemotherapy. Patients were grouped as responders (CR + PR) or non-responders (SD + PD) and results were analysed by non-parametric tests (Mann- Whitney and Wilcoxon Signed Rank Tests). Results: The median age of patients was 62 (range 24–79) with 9 patients (39%) responding to chemotherapy. Pre-chemotherapy, both total and cleaved CK18 levels were significantly lower in patients that responded to chemotherapy compared to non-responders [mean total CK18 responders 447.8U/L (95%CI 286.6–609.0 U/L ) versus mean total CK18 non-responders 999.4U/L (95%CI 602.7–1396.1 U/L), p=0.033; mean cleaved CK18 responders 174.7 U/L (95% CI 26.4–323.0) versus mean cleaved CK18 non-responders 331.4 U/L (95%CI 185.3–477.6), p=0.046]. There was a statistically significant increase in the concentration of total CK18 in the post-chemotherapy samples compared to baseline (p=0.003) however there was no association with response (p=0.12). The mean ratio of cleaved: total CK18 was significantly lower after chemotherapy [baseline 0.33 (95% CI 0.28–0.38) versus post-chemotherapy 0.29 (95%CI 0.24–0.34), p=0.01]. The mean ratio of cleaved: total CK18 at baseline was unable to discriminate between responders and non responders (p=0.83). Conclusions: These data suggest that pre-chemotherapy total and cleaved CK18 plasma levels are potential predictors of chemotherapeutic response for patients with mCRC. No significant financial relationships to disclose.