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NAP1L1: a novel human colorectal cancer biomarker derived from animal models of Apc inactivation

Queiroz, Cleberson J.S., Song, Fei, Reed, Karen R., Al-Khafaji, Nadeem, Clarke, Alan R., Vimalachandran, Dale, Miyajima, Fabio, Pritchard, D. Mark and Jenkins, John R. 2020. NAP1L1: a novel human colorectal cancer biomarker derived from animal models of Apc inactivation. Frontiers in Oncology 10 , 1565. 10.3389/fonc.2020.01565

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Abstract

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 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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Medicine
European Cancer Stem Cell Research Institute (ECSCRI)
Publisher: Frontiers Media
ISSN: 2234-943X
Date of First Compliant Deposit: 21 July 2020
Date of Acceptance: 20 July 2020
Last Modified: 11 Aug 2020 10:23
URI: http://orca.cf.ac.uk/id/eprint/133643

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