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Prognostic classification of endometrial cancer using a molecular approach based on a twelve-gene NGS panel
Endometrial Cancer (EC) is one of the most common malignancies in women in developed countries. Molecular characterization of different biotypes may improve clinical management of EC. The Cancer Genome Atlas (TCGA) project has revealed four prognostic EC subgroups: POLE, MSI; Copy Number Low (CNL) a...
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Published in: | Scientific reports 2019-12, Vol.9 (1), p.18093-9, Article 18093 |
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description | Endometrial Cancer (EC) is one of the most common malignancies in women in developed countries. Molecular characterization of different biotypes may improve clinical management of EC. The Cancer Genome Atlas (TCGA) project has revealed four prognostic EC subgroups: POLE, MSI; Copy Number Low (CNL) and Copy Number High (CNH). The goal of this study was to develop a method to classify tumors in any of the four EC prognostic groups using affordable molecular techniques. Ninety-six Formalin-Fixed Paraffin-embedded (FFPE) samples were sequenced following a NGS TruSeq Custom Amplicon low input (Illumina) protocol interrogating a multi-gene panel. MSI analysis was performed by fragment analysis using eight specific microsatellite markers. A Random Forest classification algorithm (RFA), considering NGS results, was developed to stratify EC patients into different prognostic groups. Our approach correctly classifies the EC patients into the four TCGA prognostic biotypes. The RFA assigned the samples to the CNH and CNL groups with an accuracy of 0.9753 (p |
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Molecular characterization of different biotypes may improve clinical management of EC. The Cancer Genome Atlas (TCGA) project has revealed four prognostic EC subgroups: POLE, MSI; Copy Number Low (CNL) and Copy Number High (CNH). The goal of this study was to develop a method to classify tumors in any of the four EC prognostic groups using affordable molecular techniques. Ninety-six Formalin-Fixed Paraffin-embedded (FFPE) samples were sequenced following a NGS TruSeq Custom Amplicon low input (Illumina) protocol interrogating a multi-gene panel. MSI analysis was performed by fragment analysis using eight specific microsatellite markers. A Random Forest classification algorithm (RFA), considering NGS results, was developed to stratify EC patients into different prognostic groups. Our approach correctly classifies the EC patients into the four TCGA prognostic biotypes. The RFA assigned the samples to the CNH and CNL groups with an accuracy of 0.9753 (p < 0.001). The prognostic value of these groups was prospectively reproduced on our series both for Disease-Free Survival (p = 0.004) and Overall Survival (p = 0.030).Hence, with the molecular approach herein described, a precise and suitable tool that mimics the prognostic EC subtypes has been solved and validated. Procedure that might be introduced into routine diagnostic practices.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-54624-x</identifier><identifier>PMID: 31792358</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45 ; 45/22 ; 45/23 ; 692/4017 ; 692/4028/67/1517/1931 ; 692/53/2422 ; Artificial Intelligence ; Biotypes ; Cancer ; Classification ; Copy number ; Developed countries ; Endometrial cancer ; Endometrial Neoplasms - diagnosis ; Endometrial Neoplasms - genetics ; Endometrium ; Female ; Genetic markers ; Genomes ; Humanities and Social Sciences ; Humans ; Microsatellite Instability ; Microsatellites ; multidisciplinary ; Mutation ; Mutation Rate ; Paraffin ; Prognosis ; Science ; Science (multidisciplinary) ; Survival ; Tumors</subject><ispartof>Scientific reports, 2019-12, Vol.9 (1), p.18093-9, Article 18093</ispartof><rights>The Author(s) 2019</rights><rights>2019. 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Molecular characterization of different biotypes may improve clinical management of EC. The Cancer Genome Atlas (TCGA) project has revealed four prognostic EC subgroups: POLE, MSI; Copy Number Low (CNL) and Copy Number High (CNH). The goal of this study was to develop a method to classify tumors in any of the four EC prognostic groups using affordable molecular techniques. Ninety-six Formalin-Fixed Paraffin-embedded (FFPE) samples were sequenced following a NGS TruSeq Custom Amplicon low input (Illumina) protocol interrogating a multi-gene panel. MSI analysis was performed by fragment analysis using eight specific microsatellite markers. A Random Forest classification algorithm (RFA), considering NGS results, was developed to stratify EC patients into different prognostic groups. Our approach correctly classifies the EC patients into the four TCGA prognostic biotypes. The RFA assigned the samples to the CNH and CNL groups with an accuracy of 0.9753 (p < 0.001). The prognostic value of these groups was prospectively reproduced on our series both for Disease-Free Survival (p = 0.004) and Overall Survival (p = 0.030).Hence, with the molecular approach herein described, a precise and suitable tool that mimics the prognostic EC subtypes has been solved and validated. 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Academic</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>López-Reig, Raquel</au><au>Fernández-Serra, Antonio</au><au>Romero, Ignacio</au><au>Zorrero, Cristina</au><au>Illueca, Carmen</au><au>García-Casado, Zaida</au><au>Poveda, Andrés</au><au>López-Guerrero, José Antonio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic classification of endometrial cancer using a molecular approach based on a twelve-gene NGS panel</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-12-02</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>18093</spage><epage>9</epage><pages>18093-9</pages><artnum>18093</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Endometrial Cancer (EC) is one of the most common malignancies in women in developed countries. Molecular characterization of different biotypes may improve clinical management of EC. The Cancer Genome Atlas (TCGA) project has revealed four prognostic EC subgroups: POLE, MSI; Copy Number Low (CNL) and Copy Number High (CNH). The goal of this study was to develop a method to classify tumors in any of the four EC prognostic groups using affordable molecular techniques. Ninety-six Formalin-Fixed Paraffin-embedded (FFPE) samples were sequenced following a NGS TruSeq Custom Amplicon low input (Illumina) protocol interrogating a multi-gene panel. MSI analysis was performed by fragment analysis using eight specific microsatellite markers. A Random Forest classification algorithm (RFA), considering NGS results, was developed to stratify EC patients into different prognostic groups. Our approach correctly classifies the EC patients into the four TCGA prognostic biotypes. The RFA assigned the samples to the CNH and CNL groups with an accuracy of 0.9753 (p < 0.001). The prognostic value of these groups was prospectively reproduced on our series both for Disease-Free Survival (p = 0.004) and Overall Survival (p = 0.030).Hence, with the molecular approach herein described, a precise and suitable tool that mimics the prognostic EC subtypes has been solved and validated. Procedure that might be introduced into routine diagnostic practices.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31792358</pmid><doi>10.1038/s41598-019-54624-x</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-7369-8388</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 45 45/22 45/23 692/4017 692/4028/67/1517/1931 692/53/2422 Artificial Intelligence Biotypes Cancer Classification Copy number Developed countries Endometrial cancer Endometrial Neoplasms - diagnosis Endometrial Neoplasms - genetics Endometrium Female Genetic markers Genomes Humanities and Social Sciences Humans Microsatellite Instability Microsatellites multidisciplinary Mutation Mutation Rate Paraffin Prognosis Science Science (multidisciplinary) Survival Tumors |
title | Prognostic classification of endometrial cancer using a molecular approach based on a twelve-gene NGS panel |
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