Perfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitus
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da Uninove |
Texto Completo: | http://bibliotecatede.uninove.br/handle/tede/2751 |
Resumo: | Ductal adenocarcinoma of the pancreas (CP) has a very poor prognosis and is rarely diagnosed early. There is a close association between recent-onset diabetes mellitus (DM) and this neoplasm, with DM being considered a biomarker of CP. On a clinical basis, it is difficult to differentiate DM secondary to CP and type 2 DM (DM2) and the identification of markers that can help in this differential diagnosis would be of great help in clinical practice. The aim of the present study was to compare the messenger RNA (mRNA) profile of exosomes extracted from the serum from three groups of individuals; (1) with CP and recent-onset DM, (2) with long-standing DM2, and (3) without these two clinical conditions (Control group [C]). For this purpose, 20 individuals with CP and recent-onset DM, 22 individuals with long-standing DM2 and 13 control individuals were included. Peripheral blood was collected for isolation of exosomes from 1 mL of serum; exosomes were subjected to total RNA extraction for generation of complementary DNA libraries, which were sequenced. As there was a great variability in the number of genes detected between the samples, those transcripts present in at least 30 samples were considered in the analysis of differentially expressed genes (n=113 genes.) Among these genes, those that presented a statistically significant difference in the comparisons between Groups CP and C, CP and DM and DM and C were selected (n=40 genes). A total of 19 genes were differentially expressed between participants with CP and DM: seven between CP and DM Groups (ASAH1, ULK4, TMSB4X, HBB, HBA2, YWHAB and B2M), nine between CP and C and CP and DM Groups (GIGYF2, MTND1, MTND2, DNMT3A, SHISAL2B, MAP1B, RPS29, MTCO2 and HBA1), two between CP and DM and DM and C Groups (MTND3 and DNASE1) and one between CP and C, CP and DM and DM and C Groups (MTND5). Among the 19 differentially expressed genes, seven had a P value < 0.05 in the ROC curves considering the Groups CP and DM2 (ULK4, GIGYF2, YWHAB, MTND5, MTND1, HBB and DNASE1) and could be used to discriminate recent-onset DM associated with CP from DM2, especially if these findings are validated in an independent population.b |
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Giannella, Maria Lúcia Cardillo Corrêahttp://lattes.cnpq.br/5205676344593195Giannella, Maria Lucia Cardillo Corrêahttp://lattes.cnpq.br/5205676344593195Dellê, Humbertohttp://lattes.cnpq.br/7435662740477057Mello, Ramon Andrade Bezerra dehttp://lattes.cnpq.br/4968774730306598Lacerda, Marcelo Pitombeira dehttp://lattes.cnpq.br/3171778499088240http://lattes.cnpq.br/3286300627476325Donnarumma, Carlos Del Cistia2021-11-18T14:30:30Z2021-06-30Donnarumma, Carlos Del Cistia. Perfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitus. 2021. 92 f. Tese( Programa de Mestrado em Medicina) - Universidade Nove de Julho, São Paulo.http://bibliotecatede.uninove.br/handle/tede/2751Ductal adenocarcinoma of the pancreas (CP) has a very poor prognosis and is rarely diagnosed early. There is a close association between recent-onset diabetes mellitus (DM) and this neoplasm, with DM being considered a biomarker of CP. On a clinical basis, it is difficult to differentiate DM secondary to CP and type 2 DM (DM2) and the identification of markers that can help in this differential diagnosis would be of great help in clinical practice. The aim of the present study was to compare the messenger RNA (mRNA) profile of exosomes extracted from the serum from three groups of individuals; (1) with CP and recent-onset DM, (2) with long-standing DM2, and (3) without these two clinical conditions (Control group [C]). For this purpose, 20 individuals with CP and recent-onset DM, 22 individuals with long-standing DM2 and 13 control individuals were included. Peripheral blood was collected for isolation of exosomes from 1 mL of serum; exosomes were subjected to total RNA extraction for generation of complementary DNA libraries, which were sequenced. As there was a great variability in the number of genes detected between the samples, those transcripts present in at least 30 samples were considered in the analysis of differentially expressed genes (n=113 genes.) Among these genes, those that presented a statistically significant difference in the comparisons between Groups CP and C, CP and DM and DM and C were selected (n=40 genes). A total of 19 genes were differentially expressed between participants with CP and DM: seven between CP and DM Groups (ASAH1, ULK4, TMSB4X, HBB, HBA2, YWHAB and B2M), nine between CP and C and CP and DM Groups (GIGYF2, MTND1, MTND2, DNMT3A, SHISAL2B, MAP1B, RPS29, MTCO2 and HBA1), two between CP and DM and DM and C Groups (MTND3 and DNASE1) and one between CP and C, CP and DM and DM and C Groups (MTND5). Among the 19 differentially expressed genes, seven had a P value < 0.05 in the ROC curves considering the Groups CP and DM2 (ULK4, GIGYF2, YWHAB, MTND5, MTND1, HBB and DNASE1) and could be used to discriminate recent-onset DM associated with CP from DM2, especially if these findings are validated in an independent population.bO adenocarcinoma ductal de pâncreas (CP) apresenta um prognóstico bastante reservado e raramente é diagnóstico precocemente. Existe uma estreita associação entre diabetes mellitus (DM) de início recente e essa neoplasia, sendo o DM considerado um biomarcador do CP. Em bases clínicas, é difícil diferenciar um DM secundário ao CP e o DM tipo 2 (DM2) e a identificação de marcadores que possam auxiliar nesse diagnóstico diferencial seria de grande auxílio na prática clínica. O objetivo do presente estudo foi comparar o perfil de RNA mensageiro (mRNA) de exossomas extraídos de soro de três grupos de indivíduos; (1) com CP e DM de início recente, (2) com DM2 de longa duração e (3) sem essas duas condições clínicas (Grupo controle [C]). Para tanto, foram incluídos 20 indivíduos com CP e DM de início recente, 22 indivíduos com DM2 de longa duração e 13 indivíduos no Grupo C. Sangue periférico foi coletado para isolamento de exossomas a partir de 1 mL de soro; os exossomas foram submetidos à extração de RNA total, o qual foi utilizado para a construção de bibliotecas de DNA complementar, que foram sequenciadas. Como houve uma grande variabilidade no número de genes detectados entre as amostras, foram considerados na análise de genes diferencialmente expressos aqueles que apresentaram transcritos presentes em pelo menos 30 amostras, o que resultou em 113 genes. Dentre esses genes, foram selecionados os que apresentaram diferença estatisticamente significante nas comparações entre os Grupos CP e C, CP e DM e DM e C, o que resultou em 40 genes. Um total de 19 genes foi diferencialmente expressos entre participantes com CP e DM: sete entre os Grupos CP e DM (ASAH1, ULK4, TMSB4X, HBB, HBA2, YWHAB e B2M), nove entre os Grupos CP e C e CP e DM (GIGYF2, MTND1, MTND2, DNMT3A, SHISAL2B, MAP1B, RPS29, MTCO2 e HBA1), dois entre os Grupos CP e DM e DM e C (MTND3 e DNASE1) e um entre os Grupos CP e C, CP e DM e DM e C (MTND5). Dentre os 19 genes diferencialmente expressos, sete apresentaram um valor de P < 0,05 nas curvas ROC considerando os Grupos CP e DM2 (ULK4, GIGYF2, YWHAB, MTND5, MTND1, HBB e DNASE1) e poderiam ser usados para discriminar DM de início recente associado ao CP de DM2, especialmente se esses achados forem validados em uma população independente.Submitted by Nadir Basilio (nadirsb@uninove.br) on 2021-11-18T14:30:30Z No. of bitstreams: 1 Carlos Donnarumma.pdf: 7037603 bytes, checksum: c9a5a890351d40d6dcbcb73ef4da47f0 (MD5)Made available in DSpace on 2021-11-18T14:30:30Z (GMT). No. of bitstreams: 1 Carlos Donnarumma.pdf: 7037603 bytes, checksum: c9a5a890351d40d6dcbcb73ef4da47f0 (MD5) Previous issue date: 2021-06-30application/pdfporUniversidade Nove de JulhoPrograma de Mestrado em MedicinaUNINOVEBrasilSaúdeadenocarcinoma ductal de pâncreasdiabetes mellitusexossomastranscriptomapancreatic ductal adenocarcinomadiabetes mellitusexosomestranscriptomeCIENCIAS DA SAUDEPerfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitusMessenger RNA profile of serum exosomes from individuals with pancreatic adenocarcinoma with diabetes mellitusinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis8765449414823306929600info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da Uninoveinstname:Universidade Nove de Julho (UNINOVE)instacron:UNINOVELICENSElicense.txtlicense.txttext/plain; charset=utf-82165http://localhost:8080/tede/bitstream/tede/2751/3/license.txtbd3efa91386c1718a7f26a329fdcb468MD53ORIGINALCarlos Donnarumma.pdfCarlos Donnarumma.pdfapplication/pdf7037603http://localhost:8080/tede/bitstream/tede/2751/2/Carlos+Donnarumma.pdfc9a5a890351d40d6dcbcb73ef4da47f0MD52tede/27512021-11-18 12:30:30.78oai:localhost: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Biblioteca Digital de Teses e Dissertaçõeshttp://bibliotecatede.uninove.br/PRIhttp://bibliotecatede.uninove.br/oai/requestbibliotecatede@uninove.br||bibliotecatede@uninove.bropendoar:2021-11-18T14:30:30Biblioteca Digital de Teses e Dissertações da Uninove - Universidade Nove de Julho (UNINOVE)false |
dc.title.por.fl_str_mv |
Perfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitus |
dc.title.alternative.eng.fl_str_mv |
Messenger RNA profile of serum exosomes from individuals with pancreatic adenocarcinoma with diabetes mellitus |
title |
Perfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitus |
spellingShingle |
Perfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitus Donnarumma, Carlos Del Cistia adenocarcinoma ductal de pâncreas diabetes mellitus exossomas transcriptoma pancreatic ductal adenocarcinoma diabetes mellitus exosomes transcriptome CIENCIAS DA SAUDE |
title_short |
Perfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitus |
title_full |
Perfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitus |
title_fullStr |
Perfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitus |
title_full_unstemmed |
Perfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitus |
title_sort |
Perfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitus |
author |
Donnarumma, Carlos Del Cistia |
author_facet |
Donnarumma, Carlos Del Cistia |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Giannella, Maria Lúcia Cardillo Corrêa |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5205676344593195 |
dc.contributor.referee1.fl_str_mv |
Giannella, Maria Lucia Cardillo Corrêa |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/5205676344593195 |
dc.contributor.referee2.fl_str_mv |
Dellê, Humberto |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/7435662740477057 |
dc.contributor.referee3.fl_str_mv |
Mello, Ramon Andrade Bezerra de |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/4968774730306598 |
dc.contributor.referee4.fl_str_mv |
Lacerda, Marcelo Pitombeira de |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/3171778499088240 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3286300627476325 |
dc.contributor.author.fl_str_mv |
Donnarumma, Carlos Del Cistia |
contributor_str_mv |
Giannella, Maria Lúcia Cardillo Corrêa Giannella, Maria Lucia Cardillo Corrêa Dellê, Humberto Mello, Ramon Andrade Bezerra de Lacerda, Marcelo Pitombeira de |
dc.subject.por.fl_str_mv |
adenocarcinoma ductal de pâncreas diabetes mellitus exossomas transcriptoma |
topic |
adenocarcinoma ductal de pâncreas diabetes mellitus exossomas transcriptoma pancreatic ductal adenocarcinoma diabetes mellitus exosomes transcriptome CIENCIAS DA SAUDE |
dc.subject.eng.fl_str_mv |
pancreatic ductal adenocarcinoma diabetes mellitus exosomes transcriptome |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE |
description |
Ductal adenocarcinoma of the pancreas (CP) has a very poor prognosis and is rarely diagnosed early. There is a close association between recent-onset diabetes mellitus (DM) and this neoplasm, with DM being considered a biomarker of CP. On a clinical basis, it is difficult to differentiate DM secondary to CP and type 2 DM (DM2) and the identification of markers that can help in this differential diagnosis would be of great help in clinical practice. The aim of the present study was to compare the messenger RNA (mRNA) profile of exosomes extracted from the serum from three groups of individuals; (1) with CP and recent-onset DM, (2) with long-standing DM2, and (3) without these two clinical conditions (Control group [C]). For this purpose, 20 individuals with CP and recent-onset DM, 22 individuals with long-standing DM2 and 13 control individuals were included. Peripheral blood was collected for isolation of exosomes from 1 mL of serum; exosomes were subjected to total RNA extraction for generation of complementary DNA libraries, which were sequenced. As there was a great variability in the number of genes detected between the samples, those transcripts present in at least 30 samples were considered in the analysis of differentially expressed genes (n=113 genes.) Among these genes, those that presented a statistically significant difference in the comparisons between Groups CP and C, CP and DM and DM and C were selected (n=40 genes). A total of 19 genes were differentially expressed between participants with CP and DM: seven between CP and DM Groups (ASAH1, ULK4, TMSB4X, HBB, HBA2, YWHAB and B2M), nine between CP and C and CP and DM Groups (GIGYF2, MTND1, MTND2, DNMT3A, SHISAL2B, MAP1B, RPS29, MTCO2 and HBA1), two between CP and DM and DM and C Groups (MTND3 and DNASE1) and one between CP and C, CP and DM and DM and C Groups (MTND5). Among the 19 differentially expressed genes, seven had a P value < 0.05 in the ROC curves considering the Groups CP and DM2 (ULK4, GIGYF2, YWHAB, MTND5, MTND1, HBB and DNASE1) and could be used to discriminate recent-onset DM associated with CP from DM2, especially if these findings are validated in an independent population.b |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-11-18T14:30:30Z |
dc.date.issued.fl_str_mv |
2021-06-30 |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
Donnarumma, Carlos Del Cistia. Perfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitus. 2021. 92 f. Tese( Programa de Mestrado em Medicina) - Universidade Nove de Julho, São Paulo. |
dc.identifier.uri.fl_str_mv |
http://bibliotecatede.uninove.br/handle/tede/2751 |
identifier_str_mv |
Donnarumma, Carlos Del Cistia. Perfil de RNA mensageiro de exossomas de soro de indivíduos com adenocarcinoma de pâncreas com diabetes mellitus. 2021. 92 f. Tese( Programa de Mestrado em Medicina) - Universidade Nove de Julho, São Paulo. |
url |
http://bibliotecatede.uninove.br/handle/tede/2751 |
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por |
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por |
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600 |
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UNINOVE |
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Saúde |
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Universidade Nove de Julho |
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