Effect of systemic treatment on the micronuclei frequency in the peripheral blood of patients with metastatic colorectal cancer

Abstract

Colorectal cancer (CRC) is the third most diagnosed type of cancer affecting males, and the second most diagnosed type of cancer affecting females, and one of the leading causes of cancer-related mortality globally. The estimation of the micronuclei (MN) frequency in peripheral blood lymphocytes (PBLs) from patients with CRC is proposed as a prognostic/predictive easy-to-use biomarker. In this study, we aimed to investigate the effects of systemic treatment on the MN frequency in PBLs from patients with CRC in order to determine the effectiveness of the MN frequency as a biomarker. For this purpose, from 2016 to 2018, we quantified the MN frequency as a prognostic/predictive biomarker in serial samples from 25 patients with metastatic CRC (mCRC) using cytokinesis block micronucleus assay (CBMN assay). The MN frequency in the PBLs of the patients was evaluated before, during the middle and at the end of the therapy (approximately 0, 3 and 6 months). The results revealed a common pattern regarding the fluctuation in the MN frequency. Statistical analysis confirmed that when the disease response was estimated with radiological criteria, a good response was depicted at the MN frequency and vice versa. Consequently, the findings of this study suggest that the MN frequency may serve as a promising prognostic/predictive biomarker for the monitoring of the treatment response of patients with CRC.

Keywords: cytokinesis block micronucleus assay; metastatic colorectal cancer; micronuclei frequency; micronucleus; predictive biomarker; prognostic biomarker.

Figure 1.

(A) MNf of all patients for the three time-points exhibiting a mixed ‘v’ and ‘Λ’ trend. (B) MNf of the good response group presenting a shallow ‘v’ trend. (C) MNf of the stable disease group presenting a very shallow ‘v’ trend. (D) MNf of the no response group presenting a deep ‘v’ trend. MNf, micronuclei frequency.