Study the epigenetic down-regulation of Bim on colorectal cancer chemotherapy response

Abstract

Colorectal cancer (CRC) is the third most common malignancy in developed countries. It has been shown that tumor suppressor gene methylation is associated with cancer development and chemoresistance. One of such genes is Bim, a BH3 only proapoptotic member of the Bcl-2 family that was first identified as an essential mediator of apoptosis induced by microtubules damaging agents. In the present study, the association between Bim gene methylation and CRC risk and chemotherapy responsiveness was investigated using CRC and normal colon tissues. Gene methylation assessment was performed using the methylation specific PCR and quantification of gene methylation was performed using the combined bisulfate restriction analysis (COBRA) method. A significant increase in Bim gene methylation among CRC patient compared to healthy controls (P < 0.05). Moreover, a significant correlation was found between patient demographics including cancer recurrence and tumor metastasis and gene methylation (P < 0.05). In addition, a significant inverse correlation was obtained between Bim gene methylation and chemosensitivity (P < 0.05). Collectively, current results indicate that Bim gene methylation is associated with CRC development, metastasis, and chemosensitivity. Thus, prior evaluation of Bim gene methylation might aid in the diagnosis and treatment of CRC patients. Keywords: BIM, Colorectal cancer, Methylation, Chemosensitivity, Epigenetics