NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of<i>Apc</i>Inactivation

Queiroz, Cleberson JS, Song, Fei, Reed, Karen R, Al-Khafaji, Nadeem, Clarke, Alan R, Vimalachandran, Dale ORCID: 0000-0001-5817-8969, Miyajima, Fabio, Pritchard, D Mark ORCID: 0000-0001-7971-3561 and Jenkins, John R (2020) NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of<i>Apc</i>Inactivation. FRONTIERS IN ONCOLOGY, 10. 1565-.

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Abstract

<h4>Introduction</h4>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 <i>Apc</i>, 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.<h4>Materials and methods</h4>We initially compared the proteomic and transcriptomic profiles of the small intestinal epithelium of transgenic mice in which <i>Apc</i> and/or <i>Myc</i> had been inactivated. We then studied the mRNA and immunohistochemical expression of one protein that we identified to show altered expression following <i>Apc</i> 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.<h4>Results</h4><i>Nap1l1</i> mRNA expression was increased in mouse small intestine following <i>Apc</i> deletion in a <i>Myc</i> 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.<h4>Conclusion</h4><i>NAP1L1</i> expression is increased in the mouse small intestine following <i>Apc</i> 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.

Item Type:	Article
Uncontrolled Keywords:	colorectal cancer, biomarkers, Apc, prognosis, survival
Depositing User:	Symplectic Admin
Date Deposited:	11 Aug 2020 09:50
Last Modified:	11 Oct 2023 22:43
DOI:	10.3389/fonc.2020.01565
Open Access URL:	https://doi.org/10.3389/fonc.2020.01565
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3097128