AUTHOR=Queiroz Cleberson J. S. , Song Fei , Reed Karen R. , Al-Khafaji Nadeem , Clarke Alan R. , Vimalachandran Dale , Miyajima Fabio , Pritchard D. Mark , Jenkins John R. 

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

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01565

DOI=10.3389/fonc.2020.01565

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p>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 <italic>Apc</italic>, 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.</p></sec><sec><title>Materials and Methods</title><p>We initially compared the proteomic and transcriptomic profiles of the small intestinal epithelium of transgenic mice in which <italic>Apc</italic> and/or <italic>Myc</italic> had been inactivated. We then studied the mRNA and immunohistochemical expression of one protein that we identified to show altered expression following <italic>Apc</italic> 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.</p></sec><sec><title>Results</title><p><italic>Nap1l1</italic> mRNA expression was increased in mouse small intestine following <italic>Apc</italic> deletion in a <italic>Myc</italic> 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.</p></sec><sec><title>Conclusion</title><p><italic>NAP1L1</italic> expression is increased in the mouse small intestine following <italic>Apc</italic> 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.</p></sec>