Downregulation of SMOC2 expression in papillary thyroid carcinoma and its prognostic significance
Secreted Protein Acidic and Rich in Cysteine (SPARC)-related modular calcium-binding protein-2 (SMOC2), a secreted matricellular protein, is reported to be involved in various processes related to cancer progression such as regulating the cell cycle, angiogenesis, and invasion. However, its expressi...
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| description | Secreted Protein Acidic and Rich in Cysteine (SPARC)-related modular calcium-binding protein-2 (SMOC2), a secreted matricellular protein, is reported to be involved in various processes related to cancer progression such as regulating the cell cycle, angiogenesis, and invasion. However, its expression and prognostic significance in papillary thyroid carcinomas (PTCs) remains unknown. Using immunohistochemistry, we evaluated the expression profile of SMOC2 and its prognostic value in a large cohort of PTCs. Real time-PCR analysis with fresh-frozen tissues showed that SMOC2 mRNA expression in PTCs was substantially lower than the expression in matched non-cancerous thyroid tissues, consistent with the results from thyroid cancer cell lines. Immunohistochemical analysis demonstrated that SMOC2 was normally present in thyroid follicular epithelial cells and the expression level was maintained in nodular hyperplasia. However, SMOC2 expression was significantly lower in lymphocytic thyroiditis and follicular tumors including follicular adenomas and carcinomas. In particular, 38% of PTCs exhibited a complete loss of SMOC2 expression, which was associated with the presence of
BRAF
(V600E) mutation. Moreover, SMOC2 further declined during lymph node metastasis in PTCs. DNA methylation chip analysis revealed one hypermethylated CpG site in the promoter region of SMOC2 gene, suggesting an epigenetic regulation of SMOC2 in PTCs. Remarkably SMOC2 positivity was associated with improved recurrence-free survival along with female sex, tumor size, and the N stage. However, SMOC2 was not identified as an independent prognostic marker in multivariate analyses. Taken together, SMOC2 expression is significantly down-regulated in PTCs and SMOC2 positivity is closely associated with better clinical outcomes, suggesting that SMOC2 can be a prognostic marker in PTC patients. |
| doi_str_mv | 10.1038/s41598-020-61828-z |
| format | Article |
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BRAF
(V600E) mutation. Moreover, SMOC2 further declined during lymph node metastasis in PTCs. DNA methylation chip analysis revealed one hypermethylated CpG site in the promoter region of SMOC2 gene, suggesting an epigenetic regulation of SMOC2 in PTCs. Remarkably SMOC2 positivity was associated with improved recurrence-free survival along with female sex, tumor size, and the N stage. However, SMOC2 was not identified as an independent prognostic marker in multivariate analyses. Taken together, SMOC2 expression is significantly down-regulated in PTCs and SMOC2 positivity is closely associated with better clinical outcomes, suggesting that SMOC2 can be a prognostic marker in PTC patients.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-61828-z</identifier><identifier>PMID: 32184420</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/105 ; 13/106 ; 14/63 ; 42/109 ; 631/67/1857 ; 692/163/2743/1841 ; 82/51 ; Amino Acid Substitution ; Angiogenesis ; Calcium-binding protein ; Calcium-Binding Proteins - genetics ; Calcium-Binding Proteins - metabolism ; Case-Control Studies ; Cell cycle ; Cell Line, Tumor ; CpG islands ; DNA Methylation ; Down-Regulation ; Epigenesis, Genetic ; Epithelial cells ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Humanities and Social Sciences ; Humans ; Hyperplasia ; Immunohistochemistry ; Lymph nodes ; Male ; Metastases ; multidisciplinary ; Neoplasm Staging ; Osteonectin ; Papillary thyroid carcinoma ; Prognosis ; Proteins ; Proto-Oncogene Proteins B-raf - genetics ; Science ; Science (multidisciplinary) ; Sex Characteristics ; Survival Analysis ; Thyroid ; Thyroid cancer ; Thyroid Cancer, Papillary - genetics ; Thyroid Cancer, Papillary - metabolism ; Thyroid Cancer, Papillary - pathology ; Thyroid Neoplasms - genetics ; Thyroid Neoplasms - metabolism ; Thyroid Neoplasms - pathology ; Thyroiditis ; Tumor Burden ; Tumor cell lines ; Tumors</subject><ispartof>Scientific reports, 2020-03, Vol.10 (1), p.4853, Article 4853</ispartof><rights>The Author(s) 2020</rights><rights>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-c523t-b7ce06ae84d26f2a9b645fc3698b4a1ecd74def7f849ca979f44013d60be76e23</citedby><cites>FETCH-LOGICAL-c523t-b7ce06ae84d26f2a9b645fc3698b4a1ecd74def7f849ca979f44013d60be76e23</cites><orcidid>0000-0003-4683-8338 ; 0000-0003-0557-1016</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078233/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078233/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32184420$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Hye Sung</creatorcontrib><creatorcontrib>Choi, Jae Hyuck</creatorcontrib><creatorcontrib>Lee, Jae Young</creatorcontrib><creatorcontrib>Kang, JiHoon</creatorcontrib><creatorcontrib>Myung, Jae Kyung</creatorcontrib><creatorcontrib>Kim, Woo Ho</creatorcontrib><creatorcontrib>Jang, Bo Gun</creatorcontrib><title>Downregulation of SMOC2 expression in papillary thyroid carcinoma and its prognostic significance</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Secreted Protein Acidic and Rich in Cysteine (SPARC)-related modular calcium-binding protein-2 (SMOC2), a secreted matricellular protein, is reported to be involved in various processes related to cancer progression such as regulating the cell cycle, angiogenesis, and invasion. However, its expression and prognostic significance in papillary thyroid carcinomas (PTCs) remains unknown. Using immunohistochemistry, we evaluated the expression profile of SMOC2 and its prognostic value in a large cohort of PTCs. Real time-PCR analysis with fresh-frozen tissues showed that SMOC2 mRNA expression in PTCs was substantially lower than the expression in matched non-cancerous thyroid tissues, consistent with the results from thyroid cancer cell lines. Immunohistochemical analysis demonstrated that SMOC2 was normally present in thyroid follicular epithelial cells and the expression level was maintained in nodular hyperplasia. However, SMOC2 expression was significantly lower in lymphocytic thyroiditis and follicular tumors including follicular adenomas and carcinomas. In particular, 38% of PTCs exhibited a complete loss of SMOC2 expression, which was associated with the presence of
BRAF
(V600E) mutation. Moreover, SMOC2 further declined during lymph node metastasis in PTCs. DNA methylation chip analysis revealed one hypermethylated CpG site in the promoter region of SMOC2 gene, suggesting an epigenetic regulation of SMOC2 in PTCs. Remarkably SMOC2 positivity was associated with improved recurrence-free survival along with female sex, tumor size, and the N stage. However, SMOC2 was not identified as an independent prognostic marker in multivariate analyses. Taken together, SMOC2 expression is significantly down-regulated in PTCs and SMOC2 positivity is closely associated with better clinical outcomes, suggesting that SMOC2 can be a prognostic marker in PTC patients.</description><subject>13/105</subject><subject>13/106</subject><subject>14/63</subject><subject>42/109</subject><subject>631/67/1857</subject><subject>692/163/2743/1841</subject><subject>82/51</subject><subject>Amino Acid Substitution</subject><subject>Angiogenesis</subject><subject>Calcium-binding protein</subject><subject>Calcium-Binding Proteins - genetics</subject><subject>Calcium-Binding Proteins - metabolism</subject><subject>Case-Control Studies</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>CpG islands</subject><subject>DNA Methylation</subject><subject>Down-Regulation</subject><subject>Epigenesis, Genetic</subject><subject>Epithelial cells</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hyperplasia</subject><subject>Immunohistochemistry</subject><subject>Lymph nodes</subject><subject>Male</subject><subject>Metastases</subject><subject>multidisciplinary</subject><subject>Neoplasm Staging</subject><subject>Osteonectin</subject><subject>Papillary thyroid carcinoma</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Sex Characteristics</subject><subject>Survival Analysis</subject><subject>Thyroid</subject><subject>Thyroid cancer</subject><subject>Thyroid Cancer, Papillary - genetics</subject><subject>Thyroid Cancer, Papillary - metabolism</subject><subject>Thyroid Cancer, Papillary - pathology</subject><subject>Thyroid Neoplasms - genetics</subject><subject>Thyroid Neoplasms - metabolism</subject><subject>Thyroid Neoplasms - pathology</subject><subject>Thyroiditis</subject><subject>Tumor Burden</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kUFPHSEUhUlTU436B7poSLqeFi7MAJsm5rW1JhoXtmvCMDBi5sEI89rqrxd9anXTu-GGe-65J_kQek_JJ0qY_Fw4bZVsCJCmoxJkc_sG7QHhbQMM4O2LfhcdlnJFarWgOFXv0C4DKjkHsofM1_QnZjduJrOEFHHy-OLsfAXY_Z2zK-X-L0Q8mzlMk8k3eLm8ySkM2JpsQ0xrg00ccFgKnnMaYypLsLiEMQYfrInWHaAdb6biDh_fffTr-7efqx_N6fnxyerotLEtsKXphXWkM07yAToPRvUdb71lnZI9N9TZQfDBeeElV9YooTznhLKhI70TnQO2j75sfedNv3aDdXHJZtJzDuuaWycT9OtJDJd6TL-1IEICY9Xg46NBTtcbVxZ9lTY51swamBCqbQFkVcFWZXMqJTv_fIESfU9Gb8noSkY_kNG3denDy2zPK08cqoBtBaWO4ujyv9v_sb0DmrKcuQ</recordid><startdate>20200317</startdate><enddate>20200317</enddate><creator>Kim, Hye Sung</creator><creator>Choi, Jae Hyuck</creator><creator>Lee, Jae Young</creator><creator>Kang, JiHoon</creator><creator>Myung, Jae Kyung</creator><creator>Kim, Woo Ho</creator><creator>Jang, Bo Gun</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4683-8338</orcidid><orcidid>https://orcid.org/0000-0003-0557-1016</orcidid></search><sort><creationdate>20200317</creationdate><title>Downregulation of SMOC2 expression in papillary thyroid carcinoma and its prognostic significance</title><author>Kim, Hye Sung ; Choi, Jae Hyuck ; Lee, Jae Young ; Kang, JiHoon ; Myung, Jae Kyung ; Kim, Woo Ho ; Jang, Bo Gun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c523t-b7ce06ae84d26f2a9b645fc3698b4a1ecd74def7f849ca979f44013d60be76e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13/105</topic><topic>13/106</topic><topic>14/63</topic><topic>42/109</topic><topic>631/67/1857</topic><topic>692/163/2743/1841</topic><topic>82/51</topic><topic>Amino Acid Substitution</topic><topic>Angiogenesis</topic><topic>Calcium-binding protein</topic><topic>Calcium-Binding Proteins - genetics</topic><topic>Calcium-Binding Proteins - metabolism</topic><topic>Case-Control Studies</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>CpG islands</topic><topic>DNA Methylation</topic><topic>Down-Regulation</topic><topic>Epigenesis, Genetic</topic><topic>Epithelial cells</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hyperplasia</topic><topic>Immunohistochemistry</topic><topic>Lymph nodes</topic><topic>Male</topic><topic>Metastases</topic><topic>multidisciplinary</topic><topic>Neoplasm Staging</topic><topic>Osteonectin</topic><topic>Papillary thyroid carcinoma</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Sex Characteristics</topic><topic>Survival Analysis</topic><topic>Thyroid</topic><topic>Thyroid cancer</topic><topic>Thyroid Cancer, Papillary - genetics</topic><topic>Thyroid Cancer, Papillary - metabolism</topic><topic>Thyroid Cancer, Papillary - pathology</topic><topic>Thyroid Neoplasms - genetics</topic><topic>Thyroid Neoplasms - metabolism</topic><topic>Thyroid Neoplasms - pathology</topic><topic>Thyroiditis</topic><topic>Tumor Burden</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Hye Sung</creatorcontrib><creatorcontrib>Choi, Jae Hyuck</creatorcontrib><creatorcontrib>Lee, Jae Young</creatorcontrib><creatorcontrib>Kang, JiHoon</creatorcontrib><creatorcontrib>Myung, Jae Kyung</creatorcontrib><creatorcontrib>Kim, Woo Ho</creatorcontrib><creatorcontrib>Jang, Bo Gun</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science 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 Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content 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 Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Hye Sung</au><au>Choi, Jae Hyuck</au><au>Lee, Jae Young</au><au>Kang, JiHoon</au><au>Myung, Jae Kyung</au><au>Kim, Woo Ho</au><au>Jang, Bo Gun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Downregulation of SMOC2 expression in papillary thyroid carcinoma and its prognostic significance</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-03-17</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>4853</spage><pages>4853-</pages><artnum>4853</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Secreted Protein Acidic and Rich in Cysteine (SPARC)-related modular calcium-binding protein-2 (SMOC2), a secreted matricellular protein, is reported to be involved in various processes related to cancer progression such as regulating the cell cycle, angiogenesis, and invasion. However, its expression and prognostic significance in papillary thyroid carcinomas (PTCs) remains unknown. Using immunohistochemistry, we evaluated the expression profile of SMOC2 and its prognostic value in a large cohort of PTCs. Real time-PCR analysis with fresh-frozen tissues showed that SMOC2 mRNA expression in PTCs was substantially lower than the expression in matched non-cancerous thyroid tissues, consistent with the results from thyroid cancer cell lines. Immunohistochemical analysis demonstrated that SMOC2 was normally present in thyroid follicular epithelial cells and the expression level was maintained in nodular hyperplasia. However, SMOC2 expression was significantly lower in lymphocytic thyroiditis and follicular tumors including follicular adenomas and carcinomas. In particular, 38% of PTCs exhibited a complete loss of SMOC2 expression, which was associated with the presence of
BRAF
(V600E) mutation. Moreover, SMOC2 further declined during lymph node metastasis in PTCs. DNA methylation chip analysis revealed one hypermethylated CpG site in the promoter region of SMOC2 gene, suggesting an epigenetic regulation of SMOC2 in PTCs. Remarkably SMOC2 positivity was associated with improved recurrence-free survival along with female sex, tumor size, and the N stage. However, SMOC2 was not identified as an independent prognostic marker in multivariate analyses. Taken together, SMOC2 expression is significantly down-regulated in PTCs and SMOC2 positivity is closely associated with better clinical outcomes, suggesting that SMOC2 can be a prognostic marker in PTC patients.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32184420</pmid><doi>10.1038/s41598-020-61828-z</doi><orcidid>https://orcid.org/0000-0003-4683-8338</orcidid><orcidid>https://orcid.org/0000-0003-0557-1016</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13/105 13/106 14/63 42/109 631/67/1857 692/163/2743/1841 82/51 Amino Acid Substitution Angiogenesis Calcium-binding protein Calcium-Binding Proteins - genetics Calcium-Binding Proteins - metabolism Case-Control Studies Cell cycle Cell Line, Tumor CpG islands DNA Methylation Down-Regulation Epigenesis, Genetic Epithelial cells Female Gene expression Gene Expression Regulation, Neoplastic Humanities and Social Sciences Humans Hyperplasia Immunohistochemistry Lymph nodes Male Metastases multidisciplinary Neoplasm Staging Osteonectin Papillary thyroid carcinoma Prognosis Proteins Proto-Oncogene Proteins B-raf - genetics Science Science (multidisciplinary) Sex Characteristics Survival Analysis Thyroid Thyroid cancer Thyroid Cancer, Papillary - genetics Thyroid Cancer, Papillary - metabolism Thyroid Cancer, Papillary - pathology Thyroid Neoplasms - genetics Thyroid Neoplasms - metabolism Thyroid Neoplasms - pathology Thyroiditis Tumor Burden Tumor cell lines Tumors |
| title | Downregulation of SMOC2 expression in papillary thyroid carcinoma and its prognostic significance |
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