Stemness Markers In Colorectal Cancer: Analysis In A Racially-Diverse Population

The diagnosis of colorectal cancer (CRC) is based on tumor-node-metastasis staging, a weak staging system due to different genetic and epigenetic backgrounds. Biological markers improve early detection and guide clinicians in subsequent therapies. Stemness molecules have the potential to identify patients at high risk of developing aggressive cancers. Herein, Zinc finger E-box binding homeobox 1 (ZEB1), Trefoil factor 3 (TFF3), Hepatoma Up-Regulate Protein (HURP), Mucin 2 (MUC2), and Cystic fibrosis transmembrane regulator (CFTR) are assessed as potential prognostic biomarkers in CRC. There were a total of (N=56) cases included in this study which were assessed by a pathologist, out of them 32 were African Americans (AA) and 24 Caucasian Americans (CA). The median follow-up for 42 surviving patients were noted to be 4.5 years (range 2.5 - 7.5 years). A tissue tumor microarray (TMA) was created using tumor stage-matched CRC tissues from AA and CA. The TMA was stained with each biomarker using immunohistochemistry (IHC) and consisted of 132 cores including both controls and tumors. The individual staining score ranged from (0-3) for both area and intensity. The product of area and intensity was used as the final score which ranged from (0-9) with 0 defining no expression and 9 as high expression. We evaluated the association for expression of all the five biomarkers with disease-free survival (DFS) in AA and CA separately. Stratification of the cohort by race revealed that in CA, high ZEB1 expression (nuclear and cytoplasmic) was associated with poor DFS (p= 0.015 for cytoplasm, p= 0.116 for nucleus). ZEB1 expression was not found to be a significant predictor of DFS in AA who are usually known to have worse CRC outcomes. These findings suggest that expression of ZEB1 may represent a marker for CRC prognosis, particularly in CA. High nuclear TFF3 expression in AA was found to be marginally associated with poorer DFS (p=0.089). However, the cytoplasmic expression of TFF3 was not significantly associated with DFS. Both the cytoplasmic and nuclear expression of HURP, MUC2, and CFTR among the AA and CA did not significantly correlate with DFS. Overall, we have identified two stemness molecules, ZEB1 and TFF3, with potential as markers for aggressiveness in CRC. Our findings also provide evidence of a possible biological basis for ethnicity-related differences with regards to stemness and regulatory factors of CRC aggressiveness. ZEB1 can contribute to be a novel biomarker to predict the prognosis of CRC in CA, and TFF3 will be a prognostic marker for AA. Future goals include collecting additional samples and follow-up of the patients to accurately estimate the prognosis. In addition, we will expand the project to the cellular and molecular basis underlining our findings. Funding sources: PCRP W81XWH-14-1-0151, UMMC Medical Student Research Program, and UMMC Office of Research. Citation Format: Ingrid C. Espinoza, Amit Reddy, Xu Zhang, Eldrin Bhanat, Logan Fair, Joy King, Elizabeth Tarsi, Tara Craft, Jesus Monico, Charulochana Subramony, Xinchun Zhou, Roy Duhe, Christopher Lahr, Christian Gomez. Stemness markers in colorectal cancer: Analysis in a racially-diverse population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4716. doi:10.1158/1538-7445.AM2017-4716