The significance of PIWI family expression in human lung embryogenesis and non-small cell lung cancer
The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recently believed to be limited to germinal stem cells. We have studied the expression of PIWI genes during human lung embryogenesis and in paired tumor and normal tissue prospectively collected from 71 resecte...
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| creator | Navarro, Alfons Tejero, Rut Viñolas, Nuria Cordeiro, Anna Marrades, Ramon M Fuster, Dolors Caritg, Oriol Moises, Jorge Muñoz, Carmen Molins, Laureano Ramirez, Josep Monzo, Mariano |
| description | The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recently believed to be limited to germinal stem cells. We have studied the expression of PIWI genes during human lung embryogenesis and in paired tumor and normal tissue prospectively collected from 71 resected non-small-cell lung cancer patients. The mRNA expression analysis showed that PIWIL1 was highly expressed in 7-week embryos and downregulated during the subsequent weeks of development. PIWIL1 was expressed in 11 of the tumor samples but in none of the normal tissue samples. These results were validated by immunohistochemistry, showing faint cytoplasmic reactivity in the PIWIL1-positive samples. Interestingly, the patients expressing PIWIL1 had a shorter time to relapse (TTR) (p = 0.006) and overall survival (OS) (p = 0.0076) than those without PIWIL1 expression. PIWIL2 and 4 were downregulated in tumor tissue in comparison to the normal tissue (p < 0.001) and the patients with lower levels of PIWIL4 had shorter TTR (p = 0.048) and OS (p = 0.033). In the multivariate analysis, PIWIL1 expression emerged as an independent prognostic marker. Using 5-Aza-dC treatment and bisulfite sequencing, we observed that PIWIL1 expression could be regulated in part by methylation. Finally, an in silico study identified a stem-cell expression signature associated with PIWIL1 expression. |
| doi_str_mv | 10.18632/oncotarget.3003 |
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We have studied the expression of PIWI genes during human lung embryogenesis and in paired tumor and normal tissue prospectively collected from 71 resected non-small-cell lung cancer patients. The mRNA expression analysis showed that PIWIL1 was highly expressed in 7-week embryos and downregulated during the subsequent weeks of development. PIWIL1 was expressed in 11 of the tumor samples but in none of the normal tissue samples. These results were validated by immunohistochemistry, showing faint cytoplasmic reactivity in the PIWIL1-positive samples. Interestingly, the patients expressing PIWIL1 had a shorter time to relapse (TTR) (p = 0.006) and overall survival (OS) (p = 0.0076) than those without PIWIL1 expression. PIWIL2 and 4 were downregulated in tumor tissue in comparison to the normal tissue (p < 0.001) and the patients with lower levels of PIWIL4 had shorter TTR (p = 0.048) and OS (p = 0.033). In the multivariate analysis, PIWIL1 expression emerged as an independent prognostic marker. Using 5-Aza-dC treatment and bisulfite sequencing, we observed that PIWIL1 expression could be regulated in part by methylation. Finally, an in silico study identified a stem-cell expression signature associated with PIWIL1 expression.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.3003</identifier><identifier>PMID: 25742785</identifier><language>eng</language><publisher>United States: Impact Journals</publisher><subject>Aged ; Aged, 80 and over ; Argonaute Proteins - genetics ; Argonaute Proteins - metabolism ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - pathology ; Carcinoma, Non-Small-Cell Lung - surgery ; Cell Line, Tumor ; Càncer de pulmó ; Disease Progression ; Disease-Free Survival ; DNA Methylation ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung - embryology ; Lung - metabolism ; Lung - surgery ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Lung Neoplasms - surgery ; Male ; Micro RNAs ; MicroRNAs ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Proportional Hazards Models ; Proteins ; Proteïnes ; Research Paper ; Risk Factors ; Time Factors ; Treatment Outcome</subject><ispartof>Oncotarget, 2015-10, Vol.6 (31), p.31544-31556</ispartof><rights>cc-by (c) Navarro Ponz, Alfons et al., 2015 info:eu-repo/semantics/openAccess <a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a></rights><rights>Copyright: © 2015 Navarro et al. 2015</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-a51163c7138282693cfb7a9981ee88157f8d31378cc3f32228b62bb00253e6163</citedby><cites>FETCH-LOGICAL-c504t-a51163c7138282693cfb7a9981ee88157f8d31378cc3f32228b62bb00253e6163</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/PMC4741623/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741623/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,26951,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25742785$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Navarro, Alfons</creatorcontrib><creatorcontrib>Tejero, Rut</creatorcontrib><creatorcontrib>Viñolas, Nuria</creatorcontrib><creatorcontrib>Cordeiro, Anna</creatorcontrib><creatorcontrib>Marrades, Ramon M</creatorcontrib><creatorcontrib>Fuster, Dolors</creatorcontrib><creatorcontrib>Caritg, Oriol</creatorcontrib><creatorcontrib>Moises, Jorge</creatorcontrib><creatorcontrib>Muñoz, Carmen</creatorcontrib><creatorcontrib>Molins, Laureano</creatorcontrib><creatorcontrib>Ramirez, Josep</creatorcontrib><creatorcontrib>Monzo, Mariano</creatorcontrib><title>The significance of PIWI family expression in human lung embryogenesis and non-small cell lung cancer</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recently believed to be limited to germinal stem cells. We have studied the expression of PIWI genes during human lung embryogenesis and in paired tumor and normal tissue prospectively collected from 71 resected non-small-cell lung cancer patients. The mRNA expression analysis showed that PIWIL1 was highly expressed in 7-week embryos and downregulated during the subsequent weeks of development. PIWIL1 was expressed in 11 of the tumor samples but in none of the normal tissue samples. These results were validated by immunohistochemistry, showing faint cytoplasmic reactivity in the PIWIL1-positive samples. Interestingly, the patients expressing PIWIL1 had a shorter time to relapse (TTR) (p = 0.006) and overall survival (OS) (p = 0.0076) than those without PIWIL1 expression. PIWIL2 and 4 were downregulated in tumor tissue in comparison to the normal tissue (p < 0.001) and the patients with lower levels of PIWIL4 had shorter TTR (p = 0.048) and OS (p = 0.033). In the multivariate analysis, PIWIL1 expression emerged as an independent prognostic marker. Using 5-Aza-dC treatment and bisulfite sequencing, we observed that PIWIL1 expression could be regulated in part by methylation. Finally, an in silico study identified a stem-cell expression signature associated with PIWIL1 expression.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Argonaute Proteins - genetics</subject><subject>Argonaute Proteins - metabolism</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Carcinoma, Non-Small-Cell Lung - surgery</subject><subject>Cell Line, Tumor</subject><subject>Càncer de pulmó</subject><subject>Disease Progression</subject><subject>Disease-Free Survival</subject><subject>DNA Methylation</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Lung - embryology</subject><subject>Lung - metabolism</subject><subject>Lung - surgery</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - surgery</subject><subject>Male</subject><subject>Micro RNAs</subject><subject>MicroRNAs</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Neoplasm Recurrence, Local</subject><subject>Proportional Hazards Models</subject><subject>Proteins</subject><subject>Proteïnes</subject><subject>Research Paper</subject><subject>Risk Factors</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>XX2</sourceid><recordid>eNpVkcFPHCEUxknTRo317qnh2MsoPIaBuTQxptVNTPRg0yNh2DezNDOwwkzj_vedXddVSR48wvt-PPgIOefsgutKwGUMLo42dTheCMbEJ3LC67IuQErx-V1-TM5y_svmIUuloT4ixyBVCUrLE4KPK6TZd8G33tngkMaWPiz-LGhrB99vKD6vE-bsY6A-0NU02ED7KXQUhyZtYocBs8_UhiUNMRR5sH1PHc7TrmrHTF_Jl9b2Gc_26yn5_evn4_VtcXd_s7i-uiucZOVYWMl5JZziQoOGqhaubZSta80RteZStXopuFDaOdEKANBNBU3DGEiB1Sw9JT9euOupGXDpMIzJ9mad_GDTxkTrzceT4Femi_9MqUpegZgB_AXg8uRMwrl3Z8ed8LDZBjAFBhSToGfN9_2lKT5NmEcz-Lz9ARswTtlwBSXIWjI5l7I9PsWcE7aH1jgzO1PNm6lma-os-fb-SQfBq4XiP6qAoIA</recordid><startdate>20151013</startdate><enddate>20151013</enddate><creator>Navarro, Alfons</creator><creator>Tejero, Rut</creator><creator>Viñolas, Nuria</creator><creator>Cordeiro, Anna</creator><creator>Marrades, Ramon M</creator><creator>Fuster, Dolors</creator><creator>Caritg, Oriol</creator><creator>Moises, Jorge</creator><creator>Muñoz, Carmen</creator><creator>Molins, Laureano</creator><creator>Ramirez, Josep</creator><creator>Monzo, Mariano</creator><general>Impact Journals</general><general>Impact Journals LLC</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>7X8</scope><scope>XX2</scope><scope>5PM</scope></search><sort><creationdate>20151013</creationdate><title>The significance of PIWI family expression in human lung embryogenesis and non-small cell lung cancer</title><author>Navarro, Alfons ; Tejero, Rut ; Viñolas, Nuria ; Cordeiro, Anna ; Marrades, Ramon M ; Fuster, Dolors ; Caritg, Oriol ; Moises, Jorge ; Muñoz, Carmen ; Molins, Laureano ; Ramirez, Josep ; Monzo, Mariano</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-a51163c7138282693cfb7a9981ee88157f8d31378cc3f32228b62bb00253e6163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Argonaute Proteins - genetics</topic><topic>Argonaute Proteins - metabolism</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Carcinoma, Non-Small-Cell Lung - surgery</topic><topic>Cell Line, Tumor</topic><topic>Càncer de pulmó</topic><topic>Disease Progression</topic><topic>Disease-Free Survival</topic><topic>DNA Methylation</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Lung - embryology</topic><topic>Lung - metabolism</topic><topic>Lung - surgery</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - surgery</topic><topic>Male</topic><topic>Micro RNAs</topic><topic>MicroRNAs</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Neoplasm Recurrence, Local</topic><topic>Proportional Hazards Models</topic><topic>Proteins</topic><topic>Proteïnes</topic><topic>Research Paper</topic><topic>Risk Factors</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><toplevel>online_resources</toplevel><creatorcontrib>Navarro, Alfons</creatorcontrib><creatorcontrib>Tejero, Rut</creatorcontrib><creatorcontrib>Viñolas, Nuria</creatorcontrib><creatorcontrib>Cordeiro, Anna</creatorcontrib><creatorcontrib>Marrades, Ramon M</creatorcontrib><creatorcontrib>Fuster, Dolors</creatorcontrib><creatorcontrib>Caritg, Oriol</creatorcontrib><creatorcontrib>Moises, Jorge</creatorcontrib><creatorcontrib>Muñoz, Carmen</creatorcontrib><creatorcontrib>Molins, Laureano</creatorcontrib><creatorcontrib>Ramirez, Josep</creatorcontrib><creatorcontrib>Monzo, Mariano</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Recercat</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Navarro, Alfons</au><au>Tejero, Rut</au><au>Viñolas, Nuria</au><au>Cordeiro, Anna</au><au>Marrades, Ramon M</au><au>Fuster, Dolors</au><au>Caritg, Oriol</au><au>Moises, Jorge</au><au>Muñoz, Carmen</au><au>Molins, Laureano</au><au>Ramirez, Josep</au><au>Monzo, Mariano</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The significance of PIWI family expression in human lung embryogenesis and non-small cell lung cancer</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2015-10-13</date><risdate>2015</risdate><volume>6</volume><issue>31</issue><spage>31544</spage><epage>31556</epage><pages>31544-31556</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recently believed to be limited to germinal stem cells. We have studied the expression of PIWI genes during human lung embryogenesis and in paired tumor and normal tissue prospectively collected from 71 resected non-small-cell lung cancer patients. The mRNA expression analysis showed that PIWIL1 was highly expressed in 7-week embryos and downregulated during the subsequent weeks of development. PIWIL1 was expressed in 11 of the tumor samples but in none of the normal tissue samples. These results were validated by immunohistochemistry, showing faint cytoplasmic reactivity in the PIWIL1-positive samples. Interestingly, the patients expressing PIWIL1 had a shorter time to relapse (TTR) (p = 0.006) and overall survival (OS) (p = 0.0076) than those without PIWIL1 expression. PIWIL2 and 4 were downregulated in tumor tissue in comparison to the normal tissue (p < 0.001) and the patients with lower levels of PIWIL4 had shorter TTR (p = 0.048) and OS (p = 0.033). In the multivariate analysis, PIWIL1 expression emerged as an independent prognostic marker. Using 5-Aza-dC treatment and bisulfite sequencing, we observed that PIWIL1 expression could be regulated in part by methylation. Finally, an in silico study identified a stem-cell expression signature associated with PIWIL1 expression.</abstract><cop>United States</cop><pub>Impact Journals</pub><pmid>25742785</pmid><doi>10.18632/oncotarget.3003</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aged, 80 and over Argonaute Proteins - genetics Argonaute Proteins - metabolism Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - pathology Carcinoma, Non-Small-Cell Lung - surgery Cell Line, Tumor Càncer de pulmó Disease Progression Disease-Free Survival DNA Methylation Female Gene Expression Profiling Gene Expression Regulation, Developmental Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Kaplan-Meier Estimate Lung - embryology Lung - metabolism Lung - surgery Lung cancer Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Lung Neoplasms - surgery Male Micro RNAs MicroRNAs Middle Aged Multivariate Analysis Neoplasm Recurrence, Local Proportional Hazards Models Proteins Proteïnes Research Paper Risk Factors Time Factors Treatment Outcome |
| title | The significance of PIWI family expression in human lung embryogenesis and non-small cell lung cancer |
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