Downregulation of six microRNAs is associated with advanced stage, lymph node metastasis and poor prognosis in small cell carcinoma of the cervix
Small cell carcinoma of the cervix (SCCC) is very rare, and due to the long time period required to recruit sufficient numbers of patients, there is a paucity of information regarding the prognostic factors associated with survival. MicroRNAs (miRNAs) have been used as cancer-related biomarkers in a...
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description | Small cell carcinoma of the cervix (SCCC) is very rare, and due to the long time period required to recruit sufficient numbers of patients, there is a paucity of information regarding the prognostic factors associated with survival. MicroRNAs (miRNAs) have been used as cancer-related biomarkers in a variety of tumor types, and the objective of this study was to determine whether microRNA expression profiles can predict clinical outcome in SCCC.
Forty-four patients with SCCC who underwent radical hysterectomy between January 2000 and October 2009 were enrolled. Using the GeneCopoeia All-in-One™ Customized Human qPCR Primer Array, the expression profiles of 30 miRNAs associated with tumor metastasis was obtained from the formalin-fixed paraffin embedded samples of all 44 patients. Seven miRNAs, has-let-7c, has-miR-10b, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly down-regulated in advanced stage SCCC patients (FIGO IB2-IV) compared to early stage SCCC patients (FIGOIB1). Among, downregulation of six miRNAs, has-let-7c, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly associated with lymph node metastasis and reduced survival in SCCC. Kaplan-Meier survival analyses revealed that SCCC patients with low expression of has-miR-100 (P = 0.019) and has-miR-125b (P = 0.020) projected a significant tendency towards poorer prognosis.
This study demonstrates that downregulation of 7 miRNA associated with advanced stage, 6 miRNAs with metastasis and 2 with poor prognosis in SCCC. Functional analysis of these miRNAs may enhance our understanding of SCCC, as altered expression of specific miRNAs may regulate the metastatic pathway and provide novel targets for therapy. |
doi_str_mv | 10.1371/journal.pone.0033762 |
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Forty-four patients with SCCC who underwent radical hysterectomy between January 2000 and October 2009 were enrolled. Using the GeneCopoeia All-in-One™ Customized Human qPCR Primer Array, the expression profiles of 30 miRNAs associated with tumor metastasis was obtained from the formalin-fixed paraffin embedded samples of all 44 patients. Seven miRNAs, has-let-7c, has-miR-10b, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly down-regulated in advanced stage SCCC patients (FIGO IB2-IV) compared to early stage SCCC patients (FIGOIB1). Among, downregulation of six miRNAs, has-let-7c, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly associated with lymph node metastasis and reduced survival in SCCC. Kaplan-Meier survival analyses revealed that SCCC patients with low expression of has-miR-100 (P = 0.019) and has-miR-125b (P = 0.020) projected a significant tendency towards poorer prognosis.
This study demonstrates that downregulation of 7 miRNA associated with advanced stage, 6 miRNAs with metastasis and 2 with poor prognosis in SCCC. Functional analysis of these miRNAs may enhance our understanding of SCCC, as altered expression of specific miRNAs may regulate the metastatic pathway and provide novel targets for therapy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0033762</identifier><identifier>PMID: 22438992</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Analysis ; Base Sequence ; Biology ; Biomarkers ; Cancer metastasis ; Cancer therapies ; Carcinoma ; Carcinoma, Small Cell - genetics ; Carcinoma, Small Cell - pathology ; Carcinoma, Small Cell - secondary ; Cell growth ; Cervical cancer ; Cervix ; Colorectal cancer ; Cytogenetics ; DNA Primers - genetics ; Down-Regulation ; Female ; Formaldehyde ; Functional analysis ; Gene Expression Profiling ; Genomes ; Gynecology ; Humans ; Hysterectomy ; Kaplan-Meier Estimate ; Laboratories ; Leukemia ; Liver cancer ; Lung cancer ; Lymph ; Lymph nodes ; Lymphatic Metastasis - genetics ; Lymphatic system ; Medical diagnosis ; Medical prognosis ; Medical research ; Medicine ; Metastases ; Metastasis ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; Middle Aged ; miRNA ; Neoplasm Staging ; Obstetrics ; Oncology ; Paraffin ; Patients ; Prognosis ; Prostate cancer ; Ribonucleic acid ; RNA ; RNA, Neoplasm - genetics ; Survival ; Uterine Cervical Neoplasms - genetics ; Uterine Cervical Neoplasms - pathology ; Women's health ; Young Adult</subject><ispartof>PloS one, 2012-03, Vol.7 (3), p.e33762-e33762</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Huang et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-c58ee0284546dee71ebaf2eac53b45a0168a713b0fe8fd54010389f073cb737b3</citedby><cites>FETCH-LOGICAL-c691t-c58ee0284546dee71ebaf2eac53b45a0168a713b0fe8fd54010389f073cb737b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306296/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306296/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22438992$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Schönbach, Christian</contributor><creatorcontrib>Huang, Long</creatorcontrib><creatorcontrib>Lin, Jia-Xin</creatorcontrib><creatorcontrib>Yu, Yan-Hong</creatorcontrib><creatorcontrib>Zhang, Mei-Yin</creatorcontrib><creatorcontrib>Wang, Hui-Yun</creatorcontrib><creatorcontrib>Zheng, Min</creatorcontrib><title>Downregulation of six microRNAs is associated with advanced stage, lymph node metastasis and poor prognosis in small cell carcinoma of the cervix</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Small cell carcinoma of the cervix (SCCC) is very rare, and due to the long time period required to recruit sufficient numbers of patients, there is a paucity of information regarding the prognostic factors associated with survival. MicroRNAs (miRNAs) have been used as cancer-related biomarkers in a variety of tumor types, and the objective of this study was to determine whether microRNA expression profiles can predict clinical outcome in SCCC.
Forty-four patients with SCCC who underwent radical hysterectomy between January 2000 and October 2009 were enrolled. Using the GeneCopoeia All-in-One™ Customized Human qPCR Primer Array, the expression profiles of 30 miRNAs associated with tumor metastasis was obtained from the formalin-fixed paraffin embedded samples of all 44 patients. Seven miRNAs, has-let-7c, has-miR-10b, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly down-regulated in advanced stage SCCC patients (FIGO IB2-IV) compared to early stage SCCC patients (FIGOIB1). Among, downregulation of six miRNAs, has-let-7c, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly associated with lymph node metastasis and reduced survival in SCCC. Kaplan-Meier survival analyses revealed that SCCC patients with low expression of has-miR-100 (P = 0.019) and has-miR-125b (P = 0.020) projected a significant tendency towards poorer prognosis.
This study demonstrates that downregulation of 7 miRNA associated with advanced stage, 6 miRNAs with metastasis and 2 with poor prognosis in SCCC. Functional analysis of these miRNAs may enhance our understanding of SCCC, as altered expression of specific miRNAs may regulate the metastatic pathway and provide novel targets for therapy.</description><subject>Adult</subject><subject>Aged</subject><subject>Analysis</subject><subject>Base Sequence</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Cancer metastasis</subject><subject>Cancer therapies</subject><subject>Carcinoma</subject><subject>Carcinoma, Small Cell - genetics</subject><subject>Carcinoma, Small Cell - pathology</subject><subject>Carcinoma, Small Cell - secondary</subject><subject>Cell growth</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Colorectal cancer</subject><subject>Cytogenetics</subject><subject>DNA Primers - genetics</subject><subject>Down-Regulation</subject><subject>Female</subject><subject>Formaldehyde</subject><subject>Functional analysis</subject><subject>Gene Expression Profiling</subject><subject>Genomes</subject><subject>Gynecology</subject><subject>Humans</subject><subject>Hysterectomy</subject><subject>Kaplan-Meier Estimate</subject><subject>Laboratories</subject><subject>Leukemia</subject><subject>Liver cancer</subject><subject>Lung cancer</subject><subject>Lymph</subject><subject>Lymph nodes</subject><subject>Lymphatic Metastasis - genetics</subject><subject>Lymphatic system</subject><subject>Medical diagnosis</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Neoplasm Staging</subject><subject>Obstetrics</subject><subject>Oncology</subject><subject>Paraffin</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Prostate cancer</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Neoplasm - genetics</subject><subject>Survival</subject><subject>Uterine Cervical Neoplasms - genetics</subject><subject>Uterine Cervical Neoplasms - pathology</subject><subject>Women's health</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tu1DAQhiMEoqXwBggsIYGQ2MWxEye5QVqVU6WKSuVwa02cSdZVYqe208Nj8MY47Lbqol6QSDmMv_knnvyTJM9Tukx5kb4_s5Mz0C9Ha3BJKeeFYA-S_bTibCEY5Q_vPO8lT7w_ozTnpRCPkz3GMl5WFdtPfn-0l8ZhN_UQtDXEtsTrKzJo5ezpt5Un2hPw3ioNARtyqcOaQHMBRsU3H6DDd6S_HsY1MbZBMmCAGPVzlmnIaK0jo7OdsXNIG-IH6HuicL6AU9rYAeaiYY0x6i701dPkUQu9x2fb-0Hy8_OnH4dfF8cnX44OV8cLJao0LFReIlJWZnkmGsQixRpahqByXmc50FSUUKS8pi2WbZNnNKVxyy0tuKoLXtT8IHm50R176-W2m16mnGUZFzwvI3G0IRoLZ3J0egB3LS1o-TdgXSfBBa16lJSh4BzbBmqVQTxKrppYWmR5UylWRa0P22pTPWCj0AQH_Y7o7orRa9nZC8k5FawSUeDNVsDZ8wl9kIP2cx_BoJ28rDJaRluwIpKv_iHv39yW6iB-vzatjWXVrClXWVHQouCCRWp5DxXPBqNFovNaHeM7CW93EiIT8Cp0MHkvj76f_j978muXfX2HXSP0Ye1tP82m9btgtgGjgb132N72OKVyHpybbsh5cOR2cGLai7v_5zbpZlL4H4G1FiY</recordid><startdate>20120316</startdate><enddate>20120316</enddate><creator>Huang, Long</creator><creator>Lin, Jia-Xin</creator><creator>Yu, Yan-Hong</creator><creator>Zhang, Mei-Yin</creator><creator>Wang, Hui-Yun</creator><creator>Zheng, Min</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120316</creationdate><title>Downregulation of six microRNAs is associated with advanced stage, lymph node metastasis and poor prognosis in small cell carcinoma of the cervix</title><author>Huang, Long ; Lin, Jia-Xin ; Yu, Yan-Hong ; Zhang, Mei-Yin ; Wang, Hui-Yun ; Zheng, Min</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-c58ee0284546dee71ebaf2eac53b45a0168a713b0fe8fd54010389f073cb737b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Analysis</topic><topic>Base Sequence</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Cancer metastasis</topic><topic>Cancer therapies</topic><topic>Carcinoma</topic><topic>Carcinoma, Small Cell - genetics</topic><topic>Carcinoma, Small Cell - pathology</topic><topic>Carcinoma, Small Cell - secondary</topic><topic>Cell growth</topic><topic>Cervical cancer</topic><topic>Cervix</topic><topic>Colorectal cancer</topic><topic>Cytogenetics</topic><topic>DNA Primers - genetics</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Formaldehyde</topic><topic>Functional analysis</topic><topic>Gene Expression Profiling</topic><topic>Genomes</topic><topic>Gynecology</topic><topic>Humans</topic><topic>Hysterectomy</topic><topic>Kaplan-Meier Estimate</topic><topic>Laboratories</topic><topic>Leukemia</topic><topic>Liver cancer</topic><topic>Lung cancer</topic><topic>Lymph</topic><topic>Lymph nodes</topic><topic>Lymphatic Metastasis - genetics</topic><topic>Lymphatic system</topic><topic>Medical diagnosis</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Long</au><au>Lin, Jia-Xin</au><au>Yu, Yan-Hong</au><au>Zhang, Mei-Yin</au><au>Wang, Hui-Yun</au><au>Zheng, Min</au><au>Schönbach, Christian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Downregulation of six microRNAs is associated with advanced stage, lymph node metastasis and poor prognosis in small cell carcinoma of the cervix</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-03-16</date><risdate>2012</risdate><volume>7</volume><issue>3</issue><spage>e33762</spage><epage>e33762</epage><pages>e33762-e33762</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Small cell carcinoma of the cervix (SCCC) is very rare, and due to the long time period required to recruit sufficient numbers of patients, there is a paucity of information regarding the prognostic factors associated with survival. MicroRNAs (miRNAs) have been used as cancer-related biomarkers in a variety of tumor types, and the objective of this study was to determine whether microRNA expression profiles can predict clinical outcome in SCCC.
Forty-four patients with SCCC who underwent radical hysterectomy between January 2000 and October 2009 were enrolled. Using the GeneCopoeia All-in-One™ Customized Human qPCR Primer Array, the expression profiles of 30 miRNAs associated with tumor metastasis was obtained from the formalin-fixed paraffin embedded samples of all 44 patients. Seven miRNAs, has-let-7c, has-miR-10b, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly down-regulated in advanced stage SCCC patients (FIGO IB2-IV) compared to early stage SCCC patients (FIGOIB1). Among, downregulation of six miRNAs, has-let-7c, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly associated with lymph node metastasis and reduced survival in SCCC. Kaplan-Meier survival analyses revealed that SCCC patients with low expression of has-miR-100 (P = 0.019) and has-miR-125b (P = 0.020) projected a significant tendency towards poorer prognosis.
This study demonstrates that downregulation of 7 miRNA associated with advanced stage, 6 miRNAs with metastasis and 2 with poor prognosis in SCCC. Functional analysis of these miRNAs may enhance our understanding of SCCC, as altered expression of specific miRNAs may regulate the metastatic pathway and provide novel targets for therapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22438992</pmid><doi>10.1371/journal.pone.0033762</doi><tpages>e33762</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Aged Analysis Base Sequence Biology Biomarkers Cancer metastasis Cancer therapies Carcinoma Carcinoma, Small Cell - genetics Carcinoma, Small Cell - pathology Carcinoma, Small Cell - secondary Cell growth Cervical cancer Cervix Colorectal cancer Cytogenetics DNA Primers - genetics Down-Regulation Female Formaldehyde Functional analysis Gene Expression Profiling Genomes Gynecology Humans Hysterectomy Kaplan-Meier Estimate Laboratories Leukemia Liver cancer Lung cancer Lymph Lymph nodes Lymphatic Metastasis - genetics Lymphatic system Medical diagnosis Medical prognosis Medical research Medicine Metastases Metastasis MicroRNA MicroRNAs MicroRNAs - genetics Middle Aged miRNA Neoplasm Staging Obstetrics Oncology Paraffin Patients Prognosis Prostate cancer Ribonucleic acid RNA RNA, Neoplasm - genetics Survival Uterine Cervical Neoplasms - genetics Uterine Cervical Neoplasms - pathology Women's health Young Adult |
title | Downregulation of six microRNAs is associated with advanced stage, lymph node metastasis and poor prognosis in small cell carcinoma of the cervix |
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