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Colorectal cancer (CRC) is the second leading cause of cancer death worldwide and most deaths result from metastases. We have analyzed animal models in which  Apc , 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 which  Apc  and/or  Myc  had been inactivated. We then studied the mRNA and immunohistochemical expression of one protein that we identified to show altered expression following  Apc  inactivation, 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   Nap1l1  mRNA expression was increased in mouse small intestine following  Apc  deletion in a  Myc  dependant 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   NAP1L1  expression is increased in the mouse small intestine following  Apc  inactivation 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.

NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation