Abstract
A common cancer among males and females, colon cancer (CC) contributes to significant cancer-related deaths. Approximately 50% of CCs metastasize. Tumor undergoing traditional chemotherapy or radiotherapy may not be completely eliminated due to cellular heterogeneity. A small subset of cells, known as cancer stem cells (CSCs), are reported to promote drug-resistance, self-renewal and metastasis in tumor. Therefore, cancer stem cells are linked to poor prognosis. In this project, we cooperated with Dr. Che Lin (Institute of Communications Engineering, NTHU), who selected 4 potential colon CSC and prognostic markers via system biology method: COPS5, CAND1, GRB2, and 14-3-3θ. They also constructed protein-protein interaction networks (PPINs) that displayed the correlation of the potential markers with the traditional markers. To validate these candidate proteins as CSC/prognostic markers, we used immunohistochemistry (IHC) to compare them with 8 traditional CSC markers, EpCAM, CD44, ALCAM, CD133, ABCB1, ABCC1, ABCG2 and ALDH1A1. We investigated the prognostic status on 8 traditional CSC markers and 4 potential CSC markers. Oue data suggested that traditional CSC markers are not accurate enough to predict patient survival in colon cancer. On the other hand, two of the potential markers, GRB2 and 14-3-3θ, showed a positive correlation with poor survival in patients, and such correlation was found to be even more significant when combining both markers (GRB2+ and 14-3-3θ+). These results suggest that GRB2 and 14-3-3θ are not only novel colon cancer stem cell (CCSC) markers, their positive combinational expression provide more accurate prognostic prediction in colon cancer patients.