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Transcription Factor Profiling Identifies Spatially Heterogenous Mediators of Follicular Thyroid Cancer Invasion
While minimally invasive follicular thyroid cancer (miFTC) generally has low risk of recurrence or death, encapsulated angioinvasive (eaFTC) or widely invasive (wiFTC) histological subtypes display significantly worse prognosis. Drivers of invasion are incompletely understood. Therefore, tissue samp...
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Published in: | Endocrine pathology 2020-12, Vol.31 (4), p.367-376 |
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container_title | Endocrine pathology |
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creator | Nicolson, Norman G. Paulsson, Johan O. Juhlin, C. Christofer Carling, Tobias Korah, Reju |
description | While minimally invasive follicular thyroid cancer (miFTC) generally has low risk of recurrence or death, encapsulated angioinvasive (eaFTC) or widely invasive (wiFTC) histological subtypes display significantly worse prognosis. Drivers of invasion are incompletely understood. Therefore, tissue samples including miFTC, eaFTC, and wiFTC tumors, as well as histologically normal thyroid adjacent to benign follicular adenomas, were selected from a cohort (
n
= 21) of thyroid tumor patients, and the gene expression of selected transcription factors was characterized with quantitative PCR. Invasion-relevant spatial expression patterns of selected transcription factors were subsequently characterized with immunohistochemistry.
E2F1
was over-expressed in all 3 subtypes (
p |
doi_str_mv | 10.1007/s12022-020-09651-0 |
format | article |
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n
= 21) of thyroid tumor patients, and the gene expression of selected transcription factors was characterized with quantitative PCR. Invasion-relevant spatial expression patterns of selected transcription factors were subsequently characterized with immunohistochemistry.
E2F1
was over-expressed in all 3 subtypes (
p
<0.01).
SP1
was differentially expressed in eaFTC and wiFTC compared with normal (
p
=0.01 and 0.04, respectively).
TCF7L2
was significantly upregulated in wiFTC specifically (
p
<0.05). While these findings were mRNA specific, immunohistochemistry of additional cancer-associated transcription factors revealed differential expression along the tumor invasive front relative to the central tumor, and histone acetylation modulators emerged as putative invasion markers. These findings may have significant implications for the interpretation of bulk gene expression analysis of thyroid tumor samples or for the development of targeted therapeutics for this rare but aggressive thyroid cancer variant.</description><identifier>ISSN: 1046-3976</identifier><identifier>ISSN: 1559-0097</identifier><identifier>EISSN: 1559-0097</identifier><identifier>DOI: 10.1007/s12022-020-09651-0</identifier><identifier>PMID: 33063251</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Acetylation ; Drug development ; Endocrinology ; Gene expression ; Histones ; Immunohistochemistry ; Immunomodulation ; Medicin och hälsovetenskap ; Medicine ; Medicine & Public Health ; Oncology ; Pathology ; Sp1 protein ; Thyroid cancer ; Transcription factors ; Tumors</subject><ispartof>Endocrine pathology, 2020-12, Vol.31 (4), p.367-376</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c605t-2f219fcc75a860307d6b535e62e9f81ea46761bc48f710ce30dc18ed12c210773</citedby><cites>FETCH-LOGICAL-c605t-2f219fcc75a860307d6b535e62e9f81ea46761bc48f710ce30dc18ed12c210773</cites><orcidid>0000-0002-5945-9081</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:144900103$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Nicolson, Norman G.</creatorcontrib><creatorcontrib>Paulsson, Johan O.</creatorcontrib><creatorcontrib>Juhlin, C. Christofer</creatorcontrib><creatorcontrib>Carling, Tobias</creatorcontrib><creatorcontrib>Korah, Reju</creatorcontrib><title>Transcription Factor Profiling Identifies Spatially Heterogenous Mediators of Follicular Thyroid Cancer Invasion</title><title>Endocrine pathology</title><addtitle>Endocr Pathol</addtitle><description>While minimally invasive follicular thyroid cancer (miFTC) generally has low risk of recurrence or death, encapsulated angioinvasive (eaFTC) or widely invasive (wiFTC) histological subtypes display significantly worse prognosis. Drivers of invasion are incompletely understood. Therefore, tissue samples including miFTC, eaFTC, and wiFTC tumors, as well as histologically normal thyroid adjacent to benign follicular adenomas, were selected from a cohort (
n
= 21) of thyroid tumor patients, and the gene expression of selected transcription factors was characterized with quantitative PCR. Invasion-relevant spatial expression patterns of selected transcription factors were subsequently characterized with immunohistochemistry.
E2F1
was over-expressed in all 3 subtypes (
p
<0.01).
SP1
was differentially expressed in eaFTC and wiFTC compared with normal (
p
=0.01 and 0.04, respectively).
TCF7L2
was significantly upregulated in wiFTC specifically (
p
<0.05). While these findings were mRNA specific, immunohistochemistry of additional cancer-associated transcription factors revealed differential expression along the tumor invasive front relative to the central tumor, and histone acetylation modulators emerged as putative invasion markers. These findings may have significant implications for the interpretation of bulk gene expression analysis of thyroid tumor samples or for the development of targeted therapeutics for this rare but aggressive thyroid cancer variant.</description><subject>Acetylation</subject><subject>Drug development</subject><subject>Endocrinology</subject><subject>Gene expression</subject><subject>Histones</subject><subject>Immunohistochemistry</subject><subject>Immunomodulation</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Oncology</subject><subject>Pathology</subject><subject>Sp1 protein</subject><subject>Thyroid cancer</subject><subject>Transcription factors</subject><subject>Tumors</subject><issn>1046-3976</issn><issn>1559-0097</issn><issn>1559-0097</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kktv1DAUhSMEog_4A6wssWETuH7ETjZIaNShIxWBxLC2PM7N1MVjBzspmn-P2xmoigQrX9nfObaOT1W9ovCWAqh3mTJgrAYGNXSyoTU8qU5p03Q1QKeelhmErHmn5El1lvMNAOUA7Hl1wjlIzhp6Wo3rZEK2yY2Ti4EsjZ1iIl9SHJx3YUtWPYbJDQ4z-TqayRnv9-QSJ0xxiyHOmXzC3pkiyiQOZBm9d3b2JpH19T5F15OFCRYTWYVbk8sVL6png_EZXx7X8-rb8mK9uKyvPn9cLT5c1VZCM9VsYLQbrFWNaSVwUL3cNLxBybAbWopGSCXpxop2UBQscugtbbGnzDIKSvHzqj745p84zhs9Jrczaa-jcfq49b1MqIsRZ7Tw3T_5McX-QfRbSIXoSqTAi_b9QVuAHfa2RJaMf2zx6CS4a72Nt1pJKVl7Z_DmaJDijxnzpHcuW_TeBCwZayYa2opOtKKgr_9Cb-KcQomyUIq2IMp_F4odKJtizgmHP4-hoO_Kow_l0aU8-r48GoqIHyMocNhierD-j-oXz8DJGQ</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Nicolson, Norman G.</creator><creator>Paulsson, Johan O.</creator><creator>Juhlin, C. Christofer</creator><creator>Carling, Tobias</creator><creator>Korah, Reju</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0002-5945-9081</orcidid></search><sort><creationdate>20201201</creationdate><title>Transcription Factor Profiling Identifies Spatially Heterogenous Mediators of Follicular Thyroid Cancer Invasion</title><author>Nicolson, Norman G. ; Paulsson, Johan O. ; Juhlin, C. Christofer ; Carling, Tobias ; Korah, Reju</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c605t-2f219fcc75a860307d6b535e62e9f81ea46761bc48f710ce30dc18ed12c210773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acetylation</topic><topic>Drug development</topic><topic>Endocrinology</topic><topic>Gene expression</topic><topic>Histones</topic><topic>Immunohistochemistry</topic><topic>Immunomodulation</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Oncology</topic><topic>Pathology</topic><topic>Sp1 protein</topic><topic>Thyroid cancer</topic><topic>Transcription factors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nicolson, Norman G.</creatorcontrib><creatorcontrib>Paulsson, Johan O.</creatorcontrib><creatorcontrib>Juhlin, C. Christofer</creatorcontrib><creatorcontrib>Carling, Tobias</creatorcontrib><creatorcontrib>Korah, Reju</creatorcontrib><collection>SpringerOpen</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Endocrine pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nicolson, Norman G.</au><au>Paulsson, Johan O.</au><au>Juhlin, C. Christofer</au><au>Carling, Tobias</au><au>Korah, Reju</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcription Factor Profiling Identifies Spatially Heterogenous Mediators of Follicular Thyroid Cancer Invasion</atitle><jtitle>Endocrine pathology</jtitle><stitle>Endocr Pathol</stitle><date>2020-12-01</date><risdate>2020</risdate><volume>31</volume><issue>4</issue><spage>367</spage><epage>376</epage><pages>367-376</pages><issn>1046-3976</issn><issn>1559-0097</issn><eissn>1559-0097</eissn><abstract>While minimally invasive follicular thyroid cancer (miFTC) generally has low risk of recurrence or death, encapsulated angioinvasive (eaFTC) or widely invasive (wiFTC) histological subtypes display significantly worse prognosis. Drivers of invasion are incompletely understood. Therefore, tissue samples including miFTC, eaFTC, and wiFTC tumors, as well as histologically normal thyroid adjacent to benign follicular adenomas, were selected from a cohort (
n
= 21) of thyroid tumor patients, and the gene expression of selected transcription factors was characterized with quantitative PCR. Invasion-relevant spatial expression patterns of selected transcription factors were subsequently characterized with immunohistochemistry.
E2F1
was over-expressed in all 3 subtypes (
p
<0.01).
SP1
was differentially expressed in eaFTC and wiFTC compared with normal (
p
=0.01 and 0.04, respectively).
TCF7L2
was significantly upregulated in wiFTC specifically (
p
<0.05). While these findings were mRNA specific, immunohistochemistry of additional cancer-associated transcription factors revealed differential expression along the tumor invasive front relative to the central tumor, and histone acetylation modulators emerged as putative invasion markers. These findings may have significant implications for the interpretation of bulk gene expression analysis of thyroid tumor samples or for the development of targeted therapeutics for this rare but aggressive thyroid cancer variant.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>33063251</pmid><doi>10.1007/s12022-020-09651-0</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5945-9081</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Acetylation Drug development Endocrinology Gene expression Histones Immunohistochemistry Immunomodulation Medicin och hälsovetenskap Medicine Medicine & Public Health Oncology Pathology Sp1 protein Thyroid cancer Transcription factors Tumors |
title | Transcription Factor Profiling Identifies Spatially Heterogenous Mediators of Follicular Thyroid Cancer Invasion |
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