The ratio of thioredoxin/Keap1 protein level is a predictor of distant metastasis in colorectal cancer.

ABSTRACT

AIM: Thioredoxin can reduce the cysteine group of Keap1 which could induce proteasome degradation of Nrf2, PGAM5 and Bcl-xL. Nrf2 regulates redox balance and Bcl-xL is anti-apoptotic and both are important in tumor progression. METHODS: The protein levels of Keap1, thioredoxin, PGAM5 and Bcl-xL in the normal and tumor tissues of 64 subjects with colorectal cancer (CRC) were determined by western blot. RESULTS: The tumor had higher Keap1 but lower PGAM5s and Bcl-xL protein expression than the normal tissue. The ratio of thioredoxin/Keap1 protein level in the normal (OR 0.12; 95% CI 0.02-0.83) or tumor tissue (OR 0.17; 95% CI 0.03-0.89) was a negative predictor for distant metastasis in CRC. CONCLUSION: Keap1-mediated degradation of PGAM5 and Bcl-xL may be active in CRC. The ratio of thioredoxin/Keap1 protein level may be useful for suggesting distant metastasis in CRC.