Loss of ZNF677 expression is a predictive biomarker for lymph node metastasis in Middle Eastern Colorectal Cancer

Abstract Zinc-finger proteins are transcription factors with a “finger-like” domain that are widely involved in many biological processes. The zinc-finger protein 677 (ZNF677) belongs to the zinc-finger protein family. Previous reports have highlighted the tumor suppressive role of ZNF677 in thyroid...

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Autores principales:	Abdul K. Siraj, Sandeep Kumar Parvathareddy, Nabil Siraj, Khadija Al-Obaisi, Saud M. Aldughaither, Hadeel M. AlManea, Hussah F. AlHussaini, Fouad Al-Dayel, Khawla S. Al-Kuraya
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/404fd3a585f3447b9d4f46cb50c7988d
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spelling	oai:doaj.org-article:404fd3a585f3447b9d4f46cb50c7988d2021-11-21T12:17:57ZLoss of ZNF677 expression is a predictive biomarker for lymph node metastasis in Middle Eastern Colorectal Cancer10.1038/s41598-021-01869-02045-2322https://doaj.org/article/404fd3a585f3447b9d4f46cb50c7988d2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01869-0https://doaj.org/toc/2045-2322Abstract Zinc-finger proteins are transcription factors with a “finger-like” domain that are widely involved in many biological processes. The zinc-finger protein 677 (ZNF677) belongs to the zinc-finger protein family. Previous reports have highlighted the tumor suppressive role of ZNF677 in thyroid and lung cancer. However, its role in colorectal cancer (CRC) has not been explored. ZNF677 protein expression was analyzed by immunohistochemistry in a large cohort of 1158 CRC patients. ZNF677 loss of expression was more frequent in CRC tissues (45.3%, 525/1158), when compared to that of normal tissue (5.1%, 11/214) (p < 0.0001) and was associated with mucinous histology (p = 0.0311), advanced pathological stage (p < 0.0001) and lymph node (LN) metastasis (p = 0.0374). Further analysis showed ZNF677 loss to be significantly enriched in LN metastatic CRC compared to overall cohort (p = 0.0258). More importantly, multivariate logistic regression analysis showed that ZNF677 loss is an independent predictor of LN metastasis in CRC (Odds ratio = 1.41; 95% confidence interval 1.05–1.87; p = 0.0203).The gain- and loss-of-function studies in CRC cell lines demonstrated that loss of ZNF677 protein expression prominently increased cell proliferation, progression of epithelial-mesenchymal transition and conferred chemoresistance, whereas its overexpression reversed the effect. In conclusion, loss of ZNF677 protein expression is common in Middle Eastern CRC and contributes to the prediction of biological aggressiveness of CRC. Therefore, ZNF677 could not only serve as a marker in predicting clinical prognosis in patient with CRC but also as a potential biomarker for personalized targeted therapy.Abdul K. SirajSandeep Kumar ParvathareddyNabil SirajKhadija Al-ObaisiSaud M. AldughaitherHadeel M. AlManeaHussah F. AlHussainiFouad Al-DayelKhawla S. Al-KurayaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Abdul K. Siraj Sandeep Kumar Parvathareddy Nabil Siraj Khadija Al-Obaisi Saud M. Aldughaither Hadeel M. AlManea Hussah F. AlHussaini Fouad Al-Dayel Khawla S. Al-Kuraya Loss of ZNF677 expression is a predictive biomarker for lymph node metastasis in Middle Eastern Colorectal Cancer
description	Abstract Zinc-finger proteins are transcription factors with a “finger-like” domain that are widely involved in many biological processes. The zinc-finger protein 677 (ZNF677) belongs to the zinc-finger protein family. Previous reports have highlighted the tumor suppressive role of ZNF677 in thyroid and lung cancer. However, its role in colorectal cancer (CRC) has not been explored. ZNF677 protein expression was analyzed by immunohistochemistry in a large cohort of 1158 CRC patients. ZNF677 loss of expression was more frequent in CRC tissues (45.3%, 525/1158), when compared to that of normal tissue (5.1%, 11/214) (p < 0.0001) and was associated with mucinous histology (p = 0.0311), advanced pathological stage (p < 0.0001) and lymph node (LN) metastasis (p = 0.0374). Further analysis showed ZNF677 loss to be significantly enriched in LN metastatic CRC compared to overall cohort (p = 0.0258). More importantly, multivariate logistic regression analysis showed that ZNF677 loss is an independent predictor of LN metastasis in CRC (Odds ratio = 1.41; 95% confidence interval 1.05–1.87; p = 0.0203).The gain- and loss-of-function studies in CRC cell lines demonstrated that loss of ZNF677 protein expression prominently increased cell proliferation, progression of epithelial-mesenchymal transition and conferred chemoresistance, whereas its overexpression reversed the effect. In conclusion, loss of ZNF677 protein expression is common in Middle Eastern CRC and contributes to the prediction of biological aggressiveness of CRC. Therefore, ZNF677 could not only serve as a marker in predicting clinical prognosis in patient with CRC but also as a potential biomarker for personalized targeted therapy.
format	article
author	Abdul K. Siraj Sandeep Kumar Parvathareddy Nabil Siraj Khadija Al-Obaisi Saud M. Aldughaither Hadeel M. AlManea Hussah F. AlHussaini Fouad Al-Dayel Khawla S. Al-Kuraya
author_facet	Abdul K. Siraj Sandeep Kumar Parvathareddy Nabil Siraj Khadija Al-Obaisi Saud M. Aldughaither Hadeel M. AlManea Hussah F. AlHussaini Fouad Al-Dayel Khawla S. Al-Kuraya
author_sort	Abdul K. Siraj
title	Loss of ZNF677 expression is a predictive biomarker for lymph node metastasis in Middle Eastern Colorectal Cancer
title_short	Loss of ZNF677 expression is a predictive biomarker for lymph node metastasis in Middle Eastern Colorectal Cancer
title_full	Loss of ZNF677 expression is a predictive biomarker for lymph node metastasis in Middle Eastern Colorectal Cancer
title_fullStr	Loss of ZNF677 expression is a predictive biomarker for lymph node metastasis in Middle Eastern Colorectal Cancer
title_full_unstemmed	Loss of ZNF677 expression is a predictive biomarker for lymph node metastasis in Middle Eastern Colorectal Cancer
title_sort	loss of znf677 expression is a predictive biomarker for lymph node metastasis in middle eastern colorectal cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/404fd3a585f3447b9d4f46cb50c7988d
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Loss of ZNF677 expression is a predictive biomarker for lymph node metastasis in Middle Eastern Colorectal Cancer

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