NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation
IntroductionColorectal 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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.01565/full |
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| author | Cleberson J. S. Queiroz Cleberson J. S. Queiroz Fei Song Fei Song Karen R. Reed Karen R. Reed Nadeem Al-Khafaji Alan R. Clarke Dale Vimalachandran Fabio Miyajima Fabio Miyajima D. Mark Pritchard John R. Jenkins |
| author_facet | Cleberson J. S. Queiroz Cleberson J. S. Queiroz Fei Song Fei Song Karen R. Reed Karen R. Reed Nadeem Al-Khafaji Alan R. Clarke Dale Vimalachandran Fabio Miyajima Fabio Miyajima D. Mark Pritchard John R. Jenkins |
| author_sort | Cleberson J. S. Queiroz |
| collection | DOAJ |
| description | IntroductionColorectal 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 MethodsWe 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.ResultsNap1l1 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.ConclusionNAP1L1 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. |
| first_indexed | 2024-12-11T06:42:13Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-11T06:42:13Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-35cd54370d2640b987a79ac9f606cf312022-12-22T01:17:11ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-08-011010.3389/fonc.2020.01565519268NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc InactivationCleberson J. S. Queiroz0Cleberson J. S. Queiroz1Fei Song2Fei Song3Karen R. Reed4Karen R. Reed5Nadeem Al-Khafaji6Alan R. Clarke7Dale Vimalachandran8Fabio Miyajima9Fabio Miyajima10D. Mark Pritchard11John R. Jenkins12Institute of Systems, Molecular and Integrative Biology, Henry Wellcome Laboratory, University of Liverpool, Liverpool, United KingdomFaculty of Medicine, Federal University of Mato Grosso (UFMT), Cuiaba, BrazilInstitute of Systems, Molecular and Integrative Biology, Henry Wellcome Laboratory, University of Liverpool, Liverpool, United KingdomINFRAFRONTIER GmbH, Neuherberg, GermanyWales Gene Park, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, United KingdomEuropean Cancer Stem Cell Research Institute, Cardiff University School of Biosciences, Cardiff, United KingdomInstitute of Systems, Molecular and Integrative Biology, Henry Wellcome Laboratory, University of Liverpool, Liverpool, United KingdomEuropean Cancer Stem Cell Research Institute, Cardiff University School of Biosciences, Cardiff, United KingdomDepartment of Colorectal Surgery, Countess of Chester Hospital NHS Foundation Trust, Chester, United KingdomInstitute of Systems, Molecular and Integrative Biology, Henry Wellcome Laboratory, University of Liverpool, Liverpool, United KingdomMolecular Epidemiology Laboratory, Oswaldo Cruz Foundation, Eusebio, BrazilInstitute of Systems, Molecular and Integrative Biology, Henry Wellcome Laboratory, University of Liverpool, Liverpool, United KingdomInstitute of Systems, Molecular and Integrative Biology, Henry Wellcome Laboratory, University of Liverpool, Liverpool, United KingdomIntroductionColorectal 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 MethodsWe 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.ResultsNap1l1 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.ConclusionNAP1L1 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.https://www.frontiersin.org/article/10.3389/fonc.2020.01565/fullcolorectal cancerbiomarkersApcNAP1L1prognosissurvival |
| spellingShingle | Cleberson J. S. Queiroz Cleberson J. S. Queiroz Fei Song Fei Song Karen R. Reed Karen R. Reed Nadeem Al-Khafaji Alan R. Clarke Dale Vimalachandran Fabio Miyajima Fabio Miyajima D. Mark Pritchard John R. Jenkins NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation Frontiers in Oncology colorectal cancer biomarkers Apc NAP1L1 prognosis survival |
| title | NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation |
| title_full | NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation |
| title_fullStr | NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation |
| title_full_unstemmed | NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation |
| title_short | NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation |
| title_sort | nap1l1 a novel human colorectal cancer biomarker derived from animal models of apc inactivation |
| topic | colorectal cancer biomarkers Apc NAP1L1 prognosis survival |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.01565/full |
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