Caspase-cleaved cytokeratin 18 fragment (M30) as marker of postoperative residual tumor load in colon cancer patients

Abstract 

Background

Soluble cytokeratin 18 (CK18; M65) and a caspase-cleaved fragment of CK18 (M30) have been used as biomarkers, corresponding to tumor cell death and apoptosis, respectively.

Methods

In the present study, M30 was quantified for the first time in serum samples of colon cancer patients pre- and postoperatively as well as during chemotherapy. Minimal residual disease (MRD) was assessed preoperatively by detection of pan-cytokeratin antibody A45-B/B3-positive cells in bone marrow aspirates.

Results

Out of 46 patients, those with colon tumors of stages I and IV had significantly elevated M30 serum concentrations compared to controls (n=23). In 31 colon cancer patients, M30 determinations were performed prior to and seven days after tumor surgery. A group of 24 patients exhibited a significant decrease of M30 in response to tumor removal, in contrast to seven patients who revealed either persistent or higher M30 levels postoperatively. The frequency of MRD was not significantly different for patients with decreasing (4/24) and persisting (3/7) M30. However, M30 correlated significantly with the increased number of recurrences within 36 months in the group with persisting M30 (4/7 versus 2/24, p=0.032; hazard ratio 8.3, p=0.016). In a group of patients (n=10) receiving capecitabine/oxaliplatin chemotherapy (CapOx), transient increases in M30 did not correlate with responses.

Conclusion

The data obtained within the present limited pilot study in colon cancer patients demonstrate that perioperative changes of M30 may indicate systemic residual tumor load and increased risk of recurrence warranting further evaluation of this marker of apoptosis in a larger prospective clinical trial.

Keywords: Colon cancer, Cytokeratin 18, Apoptosis, Caspase, Chemotherapy