Prognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression.

<h4>Background</h4>The RNA-binding protein Musashi-2 (MSI2) controls the translation of proteins that support stem cell identity and lineage determination and is associated with progression in some cancers. We assessed MSI2 as potential clinical biomarker in colorectal cancer (CRC) and t...

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Autores principales:	Leonid Kharin, Igor Bychkov, Nikolay Karnaukhov, Mark Voloshin, Rushaniya Fazliyeva, Alexander Deneka, Elena Frantsiyants, Oleg Kit, Erica Golemis, Yanis Boumber
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b18c5641b5094288a5a6b4997f017ad2
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spelling	oai:doaj.org-article:b18c5641b5094288a5a6b4997f017ad22021-12-02T20:05:10ZPrognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression.1932-620310.1371/journal.pone.0252132https://doaj.org/article/b18c5641b5094288a5a6b4997f017ad22021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252132https://doaj.org/toc/1932-6203<h4>Background</h4>The RNA-binding protein Musashi-2 (MSI2) controls the translation of proteins that support stem cell identity and lineage determination and is associated with progression in some cancers. We assessed MSI2 as potential clinical biomarker in colorectal cancer (CRC) and tubulovillous adenoma (TA) of colon mucosa.<h4>Methods</h4>We assessed 125 patients, of whom 20 had polyps of the colon (TAs), and 105 had CRC. Among 105 patients with CRC, 45 had stages I-III; among metastatic CRC (mCRC) patients, 31 had synchronous and 29 metachronous liver metastases. We used immunohistochemistry to measure MSI2 expression in matching specimens of normal tissue versus TAs, primary CRC tumors, and metastases, correlating expression to clinical outcomes. We analyzed the biological effects of depleting MSI2 expression in human CRC cells.<h4>Results</h4>MSI2 expression was significantly elevated in polyps versus primary tissue, and further significantly elevated in primary tumors and metastases. MSI2 expression correlated with decreased progression free survival (PFS) and overall survival (OS), higher tumor grade, and right-side localization (p = 0.004) of tumors. In metastases, high MSI2 expression correlated with E-cadherin expression. Knockdown of MSI2 in CRC cells suppressed proliferation, survival and clonogenic capacity, and decreased expression of TGFβ1, E-cadherin, and ZO1.<h4>Conclusion</h4>Elevated expression of MSI2 is associated with pre-cancerous TAs in the colonic mucosa, suggesting it is an early event in transformation. MSI2 expression is further elevated during CRC progression, and associated with poor prognosis. Depletion of MSI2 reduces CRC cell growth. These data imply a causative role of MSI2 overexpression at multiple stages of CRC formation and progression.Leonid KharinIgor BychkovNikolay KarnaukhovMark VoloshinRushaniya FazliyevaAlexander DenekaElena FrantsiyantsOleg KitErica GolemisYanis BoumberPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0252132 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Leonid Kharin Igor Bychkov Nikolay Karnaukhov Mark Voloshin Rushaniya Fazliyeva Alexander Deneka Elena Frantsiyants Oleg Kit Erica Golemis Yanis Boumber Prognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression.
description	<h4>Background</h4>The RNA-binding protein Musashi-2 (MSI2) controls the translation of proteins that support stem cell identity and lineage determination and is associated with progression in some cancers. We assessed MSI2 as potential clinical biomarker in colorectal cancer (CRC) and tubulovillous adenoma (TA) of colon mucosa.<h4>Methods</h4>We assessed 125 patients, of whom 20 had polyps of the colon (TAs), and 105 had CRC. Among 105 patients with CRC, 45 had stages I-III; among metastatic CRC (mCRC) patients, 31 had synchronous and 29 metachronous liver metastases. We used immunohistochemistry to measure MSI2 expression in matching specimens of normal tissue versus TAs, primary CRC tumors, and metastases, correlating expression to clinical outcomes. We analyzed the biological effects of depleting MSI2 expression in human CRC cells.<h4>Results</h4>MSI2 expression was significantly elevated in polyps versus primary tissue, and further significantly elevated in primary tumors and metastases. MSI2 expression correlated with decreased progression free survival (PFS) and overall survival (OS), higher tumor grade, and right-side localization (p = 0.004) of tumors. In metastases, high MSI2 expression correlated with E-cadherin expression. Knockdown of MSI2 in CRC cells suppressed proliferation, survival and clonogenic capacity, and decreased expression of TGFβ1, E-cadherin, and ZO1.<h4>Conclusion</h4>Elevated expression of MSI2 is associated with pre-cancerous TAs in the colonic mucosa, suggesting it is an early event in transformation. MSI2 expression is further elevated during CRC progression, and associated with poor prognosis. Depletion of MSI2 reduces CRC cell growth. These data imply a causative role of MSI2 overexpression at multiple stages of CRC formation and progression.
format	article
author	Leonid Kharin Igor Bychkov Nikolay Karnaukhov Mark Voloshin Rushaniya Fazliyeva Alexander Deneka Elena Frantsiyants Oleg Kit Erica Golemis Yanis Boumber
author_facet	Leonid Kharin Igor Bychkov Nikolay Karnaukhov Mark Voloshin Rushaniya Fazliyeva Alexander Deneka Elena Frantsiyants Oleg Kit Erica Golemis Yanis Boumber
author_sort	Leonid Kharin
title	Prognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression.
title_short	Prognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression.
title_full	Prognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression.
title_fullStr	Prognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression.
title_full_unstemmed	Prognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression.
title_sort	prognostic role and biologic features of musashi-2 expression in colon polyps and during colorectal cancer progression.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/b18c5641b5094288a5a6b4997f017ad2
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Prognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression.

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