P105 MIRNA483-3P AND MIRNA221 DYSREGULATION AND CORRELATION WITH SURVIVAL IN ESOPHAGEAL ADENOCARCINOMA (EAC)

Abstract Aim Our study aimed to characterize miR-221 and 483-3p dysregulation and to correlate their expression with clinical outcomes in patients submitted in first instance to surgical therapy (naïve patients) for esophageal adenocarcinoma (EAC). Background & Methods MicroRNA (miRNAs) are smal...

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Published in:Diseases of the esophagus 2019-11, Vol.32 (Supplement_2)
Main Authors: Isidori, F, Bozzarelli, I, Lugaresi, M, Malvi, D, Mastracci, L, Hoefnagel, S J M, Räsänen, J, Söderström, H, Raulli, G, D’Errico, A, Fiocca, R, Seri, M, Krishnadath, K K, Bonora, E, Mattioli, S
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container_issue Supplement_2
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container_title Diseases of the esophagus
container_volume 32
creator Isidori, F
Bozzarelli, I
Lugaresi, M
Malvi, D
Mastracci, L
Hoefnagel, S J M
Räsänen, J
Söderström, H
Raulli, G
D’Errico, A
Fiocca, R
Seri, M
Krishnadath, K K
Bonora, E
Mattioli, S
description Abstract Aim Our study aimed to characterize miR-221 and 483-3p dysregulation and to correlate their expression with clinical outcomes in patients submitted in first instance to surgical therapy (naïve patients) for esophageal adenocarcinoma (EAC). Background & Methods MicroRNA (miRNAs) are small, noncoding RNAs that play important roles in several biological processes by fine-tuning gene expression1. In a cohort of well-characterized EAC, we analyzed the expression of miRNAs. RNA was extracted from formalin-embedded (FFPE) surgical specimens of normal gastric tissues and EACs, classified according to BIM/GIM classification (BIM=Barrett’s intestinal metaplasia, GIM=Gastric intestinal metaplasia): 43 BIM-/GIM-, 32 BIM+/GIM-, 2 BIM+/GIM+, 9 BIM-/GIM+). Expression of 754 human miRNAs was profiled in 8 cases with TaqMan MicroRNA Array card A1.1/B3.0. miR-221 and 483-3p validation was performed with single TaqMan probes on all 85 FFPE samples. miR-221 and miR-483-3p were also analyzed in a cohort of 39 fresh-frozen biopsies (29 EAC and 10 normal esophageal tissues). In 3 EAC cell-lines (OE-19, OE-33, FLO-1)2 we tested the expression of miR-221 and miR-483-3p3 and of two major targets (PTEN and SMAD4, respectively). Correlations between miRNAs and clinical outcomes were calculated using Kruskal-Wallis, Mann-Whitney, t-Student’s and Kaplan-Meier tests. Results miR-221 and 483-3p resulted upregulated from the MicroRNA Array card analysis. This increase was confirmed in two independent cohorts (FFPE-cohort: miR-483-3p p=0.0065; fresh-frozen-cohort: miR-483-3p p
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Background &amp; Methods MicroRNA (miRNAs) are small, noncoding RNAs that play important roles in several biological processes by fine-tuning gene expression1. In a cohort of well-characterized EAC, we analyzed the expression of miRNAs. RNA was extracted from formalin-embedded (FFPE) surgical specimens of normal gastric tissues and EACs, classified according to BIM/GIM classification (BIM=Barrett’s intestinal metaplasia, GIM=Gastric intestinal metaplasia): 43 BIM-/GIM-, 32 BIM+/GIM-, 2 BIM+/GIM+, 9 BIM-/GIM+). Expression of 754 human miRNAs was profiled in 8 cases with TaqMan MicroRNA Array card A1.1/B3.0. miR-221 and 483-3p validation was performed with single TaqMan probes on all 85 FFPE samples. miR-221 and miR-483-3p were also analyzed in a cohort of 39 fresh-frozen biopsies (29 EAC and 10 normal esophageal tissues). In 3 EAC cell-lines (OE-19, OE-33, FLO-1)2 we tested the expression of miR-221 and miR-483-3p3 and of two major targets (PTEN and SMAD4, respectively). Correlations between miRNAs and clinical outcomes were calculated using Kruskal-Wallis, Mann-Whitney, t-Student’s and Kaplan-Meier tests. Results miR-221 and 483-3p resulted upregulated from the MicroRNA Array card analysis. This increase was confirmed in two independent cohorts (FFPE-cohort: miR-483-3p p=0.0065; fresh-frozen-cohort: miR-483-3p p&lt;0.0001, miR-221 p=0.0062). Statistical analysis showed an upregulation of both miRNAs, in particular miR-483-3p (p&lt;0.0001), in BIM-/GIM-, compared to BIM+/GIM-. miR-221 and 483-3p up- regulation correlated with reduced cancer-specific survival in FFPE samples (miR-483-3p p=0.053, miR-221 p=0.001). We demonstrated a significantly increase for miR-483-3p (p=0.01) with a trend toward reduction of SMAD4 expression in FLO-1 compared to other cell-lines. Conclusions We identified an up-regulation of miR-221 and miR-483-3p, which might contribute to cancer progression. In the most aggressive cell line, FLO-1, we observed an increased expression of miR-483-3p, with SMAD4 reduction. Further studies are warranted to elucidate in depth the role of miR-221 and miR- 483-3p in EAC.</description><identifier>ISSN: 1120-8694</identifier><identifier>EISSN: 1442-2050</identifier><identifier>DOI: 10.1093/dote/doz092.105</identifier><language>eng</language><publisher>Oxford University Press</publisher><ispartof>Diseases of the esophagus, 2019-11, Vol.32 (Supplement_2)</ispartof><rights>The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids></links><search><creatorcontrib>Isidori, F</creatorcontrib><creatorcontrib>Bozzarelli, I</creatorcontrib><creatorcontrib>Lugaresi, M</creatorcontrib><creatorcontrib>Malvi, D</creatorcontrib><creatorcontrib>Mastracci, L</creatorcontrib><creatorcontrib>Hoefnagel, S J M</creatorcontrib><creatorcontrib>Räsänen, J</creatorcontrib><creatorcontrib>Söderström, H</creatorcontrib><creatorcontrib>Raulli, G</creatorcontrib><creatorcontrib>D’Errico, A</creatorcontrib><creatorcontrib>Fiocca, R</creatorcontrib><creatorcontrib>Seri, M</creatorcontrib><creatorcontrib>Krishnadath, K K</creatorcontrib><creatorcontrib>Bonora, E</creatorcontrib><creatorcontrib>Mattioli, S</creatorcontrib><creatorcontrib>EACSGE</creatorcontrib><title>P105 MIRNA483-3P AND MIRNA221 DYSREGULATION AND CORRELATION WITH SURVIVAL IN ESOPHAGEAL ADENOCARCINOMA (EAC)</title><title>Diseases of the esophagus</title><description>Abstract Aim Our study aimed to characterize miR-221 and 483-3p dysregulation and to correlate their expression with clinical outcomes in patients submitted in first instance to surgical therapy (naïve patients) for esophageal adenocarcinoma (EAC). Background &amp; Methods MicroRNA (miRNAs) are small, noncoding RNAs that play important roles in several biological processes by fine-tuning gene expression1. In a cohort of well-characterized EAC, we analyzed the expression of miRNAs. RNA was extracted from formalin-embedded (FFPE) surgical specimens of normal gastric tissues and EACs, classified according to BIM/GIM classification (BIM=Barrett’s intestinal metaplasia, GIM=Gastric intestinal metaplasia): 43 BIM-/GIM-, 32 BIM+/GIM-, 2 BIM+/GIM+, 9 BIM-/GIM+). Expression of 754 human miRNAs was profiled in 8 cases with TaqMan MicroRNA Array card A1.1/B3.0. miR-221 and 483-3p validation was performed with single TaqMan probes on all 85 FFPE samples. miR-221 and miR-483-3p were also analyzed in a cohort of 39 fresh-frozen biopsies (29 EAC and 10 normal esophageal tissues). In 3 EAC cell-lines (OE-19, OE-33, FLO-1)2 we tested the expression of miR-221 and miR-483-3p3 and of two major targets (PTEN and SMAD4, respectively). Correlations between miRNAs and clinical outcomes were calculated using Kruskal-Wallis, Mann-Whitney, t-Student’s and Kaplan-Meier tests. Results miR-221 and 483-3p resulted upregulated from the MicroRNA Array card analysis. This increase was confirmed in two independent cohorts (FFPE-cohort: miR-483-3p p=0.0065; fresh-frozen-cohort: miR-483-3p p&lt;0.0001, miR-221 p=0.0062). Statistical analysis showed an upregulation of both miRNAs, in particular miR-483-3p (p&lt;0.0001), in BIM-/GIM-, compared to BIM+/GIM-. miR-221 and 483-3p up- regulation correlated with reduced cancer-specific survival in FFPE samples (miR-483-3p p=0.053, miR-221 p=0.001). We demonstrated a significantly increase for miR-483-3p (p=0.01) with a trend toward reduction of SMAD4 expression in FLO-1 compared to other cell-lines. Conclusions We identified an up-regulation of miR-221 and miR-483-3p, which might contribute to cancer progression. In the most aggressive cell line, FLO-1, we observed an increased expression of miR-483-3p, with SMAD4 reduction. Further studies are warranted to elucidate in depth the role of miR-221 and miR- 483-3p in EAC.</description><issn>1120-8694</issn><issn>1442-2050</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFUMFOg0AQ3RhNrNWz1z2qCXZ2YYE9bmCFTSgQoDWeCIUl0dTQQD3o17uV3r3MzHvz3mTyELon8EyA26tuOGpTfoBTQ7ALtCCOQy0KDC7NTChYvsuda3QzTR8AxLNdf4H2udHitSpS4fi2ZedYpOGMKSU4fCsLGW0SUaks_VsFWVHIM35VVYzLTbFVW5FglWJZZnksImmQCGWaBaIIVJqtBX6QIni8RVd9s5_03bkvUfUiqyC2kixSgUis1mPM8sHfmW8po63mvOm7hnANngsO6TygfqsbboPHvdbVmvbujoLWQPqOd0BYR-wlWs1n23GYplH39WF8_2zG75pAfcqqPmVVz1kZghnH0-wYvg7_in8BJr5iOg</recordid><startdate>20191123</startdate><enddate>20191123</enddate><creator>Isidori, F</creator><creator>Bozzarelli, I</creator><creator>Lugaresi, M</creator><creator>Malvi, D</creator><creator>Mastracci, L</creator><creator>Hoefnagel, S J M</creator><creator>Räsänen, J</creator><creator>Söderström, H</creator><creator>Raulli, G</creator><creator>D’Errico, A</creator><creator>Fiocca, R</creator><creator>Seri, M</creator><creator>Krishnadath, K K</creator><creator>Bonora, E</creator><creator>Mattioli, S</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20191123</creationdate><title>P105 MIRNA483-3P AND MIRNA221 DYSREGULATION AND CORRELATION WITH SURVIVAL IN ESOPHAGEAL ADENOCARCINOMA (EAC)</title><author>Isidori, F ; Bozzarelli, I ; Lugaresi, M ; Malvi, D ; Mastracci, L ; Hoefnagel, S J M ; Räsänen, J ; Söderström, H ; Raulli, G ; D’Errico, A ; Fiocca, R ; Seri, M ; Krishnadath, K K ; Bonora, E ; Mattioli, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c755-808b120252ce99afda19e076041d7028cea930797c6ee2f6b20ee01fd9d015d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Isidori, F</creatorcontrib><creatorcontrib>Bozzarelli, I</creatorcontrib><creatorcontrib>Lugaresi, M</creatorcontrib><creatorcontrib>Malvi, D</creatorcontrib><creatorcontrib>Mastracci, L</creatorcontrib><creatorcontrib>Hoefnagel, S J M</creatorcontrib><creatorcontrib>Räsänen, J</creatorcontrib><creatorcontrib>Söderström, H</creatorcontrib><creatorcontrib>Raulli, G</creatorcontrib><creatorcontrib>D’Errico, A</creatorcontrib><creatorcontrib>Fiocca, R</creatorcontrib><creatorcontrib>Seri, M</creatorcontrib><creatorcontrib>Krishnadath, K K</creatorcontrib><creatorcontrib>Bonora, E</creatorcontrib><creatorcontrib>Mattioli, S</creatorcontrib><creatorcontrib>EACSGE</creatorcontrib><collection>CrossRef</collection><jtitle>Diseases of the esophagus</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Isidori, F</au><au>Bozzarelli, I</au><au>Lugaresi, M</au><au>Malvi, D</au><au>Mastracci, L</au><au>Hoefnagel, S J M</au><au>Räsänen, J</au><au>Söderström, H</au><au>Raulli, G</au><au>D’Errico, A</au><au>Fiocca, R</au><au>Seri, M</au><au>Krishnadath, K K</au><au>Bonora, E</au><au>Mattioli, S</au><aucorp>EACSGE</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>P105 MIRNA483-3P AND MIRNA221 DYSREGULATION AND CORRELATION WITH SURVIVAL IN ESOPHAGEAL ADENOCARCINOMA (EAC)</atitle><jtitle>Diseases of the esophagus</jtitle><date>2019-11-23</date><risdate>2019</risdate><volume>32</volume><issue>Supplement_2</issue><issn>1120-8694</issn><eissn>1442-2050</eissn><abstract>Abstract Aim Our study aimed to characterize miR-221 and 483-3p dysregulation and to correlate their expression with clinical outcomes in patients submitted in first instance to surgical therapy (naïve patients) for esophageal adenocarcinoma (EAC). Background &amp; Methods MicroRNA (miRNAs) are small, noncoding RNAs that play important roles in several biological processes by fine-tuning gene expression1. In a cohort of well-characterized EAC, we analyzed the expression of miRNAs. RNA was extracted from formalin-embedded (FFPE) surgical specimens of normal gastric tissues and EACs, classified according to BIM/GIM classification (BIM=Barrett’s intestinal metaplasia, GIM=Gastric intestinal metaplasia): 43 BIM-/GIM-, 32 BIM+/GIM-, 2 BIM+/GIM+, 9 BIM-/GIM+). Expression of 754 human miRNAs was profiled in 8 cases with TaqMan MicroRNA Array card A1.1/B3.0. miR-221 and 483-3p validation was performed with single TaqMan probes on all 85 FFPE samples. miR-221 and miR-483-3p were also analyzed in a cohort of 39 fresh-frozen biopsies (29 EAC and 10 normal esophageal tissues). In 3 EAC cell-lines (OE-19, OE-33, FLO-1)2 we tested the expression of miR-221 and miR-483-3p3 and of two major targets (PTEN and SMAD4, respectively). Correlations between miRNAs and clinical outcomes were calculated using Kruskal-Wallis, Mann-Whitney, t-Student’s and Kaplan-Meier tests. Results miR-221 and 483-3p resulted upregulated from the MicroRNA Array card analysis. This increase was confirmed in two independent cohorts (FFPE-cohort: miR-483-3p p=0.0065; fresh-frozen-cohort: miR-483-3p p&lt;0.0001, miR-221 p=0.0062). Statistical analysis showed an upregulation of both miRNAs, in particular miR-483-3p (p&lt;0.0001), in BIM-/GIM-, compared to BIM+/GIM-. miR-221 and 483-3p up- regulation correlated with reduced cancer-specific survival in FFPE samples (miR-483-3p p=0.053, miR-221 p=0.001). We demonstrated a significantly increase for miR-483-3p (p=0.01) with a trend toward reduction of SMAD4 expression in FLO-1 compared to other cell-lines. Conclusions We identified an up-regulation of miR-221 and miR-483-3p, which might contribute to cancer progression. In the most aggressive cell line, FLO-1, we observed an increased expression of miR-483-3p, with SMAD4 reduction. Further studies are warranted to elucidate in depth the role of miR-221 and miR- 483-3p in EAC.</abstract><pub>Oxford University Press</pub><doi>10.1093/dote/doz092.105</doi></addata></record>
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title P105 MIRNA483-3P AND MIRNA221 DYSREGULATION AND CORRELATION WITH SURVIVAL IN ESOPHAGEAL ADENOCARCINOMA (EAC)
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