NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models ofApcInactivation

Introduction Colorectal cancer (CRC) is the second leading cause of cancer death worldwide and most deaths result from metastases. We have analyzed animal models in whichApc, a gene that is frequently mutated during the early stages of colorectal carcinogenesis, was inactivated and human samples to try to identify novel potential biomarkers for CRC. Materials and Methods We initially compared the proteomic and transcriptomic profiles of the small intestinal epithelium of transgenic mice in whichApcand/orMychad been inactivated. We then studied the mRNA and immunohistochemical expression of one protein that we identified to show altered expression followingApcinactivation, nucleosome assembly protein 1-like 1 (NAP1L1) in human CRC samples and performed a prognostic correlation between biomarker expression and survival in CRC patients. Results Nap1l1mRNA expression was increased in mouse small intestine followingApcdeletion in aMycdependant manner and was also increased in human CRC samples. Immunohistochemical NAP1L1 expression was decreased in human CRC samples relative to matched adjacent normal colonic tissue. In a separate cohort of 75 CRC patients, we found a strong correlation between NAP1L1 nuclear expression and overall survival in those patients who had stage III and IV cancers. Conclusion NAP1L1expression is increased in the mouse small intestine followingApcinactivation and its expression is also altered in human CRC. Immunohistochemical NAP1L1 nuclear expression correlated with overall survival in a cohort of CRC patients. Further studies are now required to clarify the role of this protein in CRC.