The prognostic value of combining CD133 and mismatch repair proteins in patients with colorectal cancer

The prognostic value of cancer stem cells (CSCs) is a hot topic in colorectal carcinoma (CRC) research. CD133 has been identified as an important colorectal CSC marker, but its prognostic significance remains controversial. Recently, studies have reported a possible functional link between CSCs and DNA mismatch repair (MMR) system. However, the relationship between CRC stemness and MMR proteins remains little explored, and whether the predictive role of CD133 is affected by MMR proteins is still unknown. The aim of our study is to investigate the influence of MMR proteins on the predictive significance of CD133 in terms of CRC patient survival and to further analyze the correlation between MMR proteins and cancer stemness. In our study, we didn't observe the prognostic value of CD133 in CRC patients. However, we demonstrated that in patients with low expression of MSH6, MSH2, PMS2 and MLH1, especially MSH6, CD133 was an effective prognostic biomarker. Moreover, correlation analysis revealed a positive correlation between MSH6 and CD133 expression. In vitro studies supported our clinical data and showed that the expression of cancer-associated stemness markers CD133, BMI-1, OCT-4 and SOX-2 was significantly decreased in siRNA-MSH6/MLH1 CRC cells. Thus, our results demonstrated that MMR proteins might play an important role in modulating the stemness of CRC cells. MMR proteins might be a crucial determinant that can help to accurately identify tumour subclones that may benefit from using the CSC marker CD133 as a prognostic marker.