PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study

Background: Patients with advanced cirrhosis are at high risk of developing clinically significant portal hypertension (CSPH). We analyzed the gene expression profile of peripheral blood mononuclear cells (PBMCs) from HIV/HCV coinfected patients to identify a gene expression signature of advanced ci...

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Autores: Salgüero, Sergio, Brochado-Kith, Óscar, Verdices, Ana Virseda, Berenguer, Juan, González García, Juan Julián, Martínez, Isidoro, Díez, Cristina, Hontañón Antoñana, Víctor, Pérez-Latorre, Leire, Fernández-Rodríguez, Amanda, Jiménez-Sousa, María Ángeles, Resino, Salvador
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/709802
Acceso en línea:http://hdl.handle.net/10486/709802
https://dx.doi.org/10.1016/j.biopha.2023.114220
Access Level:acceso abierto
Palabra clave:Advanced cirrhosis
Gene expression
HIV/HCV coinfection
Liver stiffness
PBMCs
RNA-seq
Medicina
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spelling PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control studySalgüero, SergioBrochado-Kith, ÓscarVerdices, Ana VirsedaBerenguer, JuanGonzález García, Juan JuliánMartínez, IsidoroDíez, CristinaHontañón Antoñana, VíctorPérez-Latorre, LeireFernández-Rodríguez, AmandaJiménez-Sousa, María ÁngelesResino, SalvadorAdvanced cirrhosisGene expressionHIV/HCV coinfectionLiver stiffnessPBMCsRNA-seqMedicinaBackground: Patients with advanced cirrhosis are at high risk of developing clinically significant portal hypertension (CSPH). We analyzed the gene expression profile of peripheral blood mononuclear cells (PBMCs) from HIV/HCV coinfected patients to identify a gene expression signature of advanced cirrhosis with high risk for CSPH. Methods: We conducted a cross-sectional study on 68 patients. Liver stiffness measurement (LSM) was used to stratify patients into < 12.5 kPa (no cirrhosis, n = 19), 12.5 – 24.9 kPa (cirrhosis, n = 20), and ≥ 25 kPa (advanced cirrhosis with high risk for CSPH, n = 29). Besides, we further evaluated LSM < 25 kPa (n = 39) vs. ≥ 25 kPa (n = 29). Total RNA was extracted from PBMCs, and poly(A) RNA sequencing was performed. Two significant differentially expressed (SDE) transcripts were validated by quantitative PCR in a different cohort (n = 46). Results: We found 60 SDE transcripts between patients with LSM < 12.5 kPa and ≥ 25 kPa. Partial least squares discriminant analysis showed that those 60 SDE transcripts collectively discriminated LSM ≥ 25 kPa, with an area under the receiver operating characteristic curve (AUROC) of 0.84. Eight genes had an AUROC ≥ 0.75 for LSM ≥ 25 kPa: five were positively associated with LSM values (SCAMP1, ABHD17B, GPR146, GTF2A1, and TMEM64), while three were inversely associated (ZFHX2-AS1, MDK, and STAG3L2). We validated the two SDE transcripts with the highest discrimination capacity in a different cohort, finding significant differences between < 25 kPa and ≥ 25 kPa (MDK (p = 0.006) and STAG3L2 (p = 0.021)). Conclusions: A gene expression signature of 60 transcripts was associated with advanced cirrhosis with high risk for CSPH in HIV/HCV coinfected patientsThis study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers CP17CIII/00007 and PI18CIII/00028 to MAJS, PI17/00657 and PI20/00474 to JB, PI17/00903 and PI20/00507 to JGG, PI18CIII/00020 to AFR, and PI17CIII/00003 and PI20CIII/00004 to SR) and Ministerio de Ciencia e Innovacion ´ (AEI, PID2021-126781OB-I00 to AFR). The study was also funded by the CIBER -Consorcio Centro de Investigacion ´ Biom´edica en Red- (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion ´ and Union ´ Europea – NextGenerationEU (CB21/13/00044)ElsevierDepartamento de MedicinaFacultad de Medicina20232023-01-09research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/709802https://dx.doi.org/10.1016/j.biopha.2023.114220reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7098022026-06-23T12:46:27Z
dc.title.none.fl_str_mv PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study
title PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study
spellingShingle PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study
Salgüero, Sergio
Advanced cirrhosis
Gene expression
HIV/HCV coinfection
Liver stiffness
PBMCs
RNA-seq
Medicina
title_short PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study
title_full PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study
title_fullStr PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study
title_full_unstemmed PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study
title_sort PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study
dc.creator.none.fl_str_mv Salgüero, Sergio
Brochado-Kith, Óscar
Verdices, Ana Virseda
Berenguer, Juan
González García, Juan Julián
Martínez, Isidoro
Díez, Cristina
Hontañón Antoñana, Víctor
Pérez-Latorre, Leire
Fernández-Rodríguez, Amanda
Jiménez-Sousa, María Ángeles
Resino, Salvador
author Salgüero, Sergio
author_facet Salgüero, Sergio
Brochado-Kith, Óscar
Verdices, Ana Virseda
Berenguer, Juan
González García, Juan Julián
Martínez, Isidoro
Díez, Cristina
Hontañón Antoñana, Víctor
Pérez-Latorre, Leire
Fernández-Rodríguez, Amanda
Jiménez-Sousa, María Ángeles
Resino, Salvador
author_role author
author2 Brochado-Kith, Óscar
Verdices, Ana Virseda
Berenguer, Juan
González García, Juan Julián
Martínez, Isidoro
Díez, Cristina
Hontañón Antoñana, Víctor
Pérez-Latorre, Leire
Fernández-Rodríguez, Amanda
Jiménez-Sousa, María Ángeles
Resino, Salvador
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
dc.subject.none.fl_str_mv Advanced cirrhosis
Gene expression
HIV/HCV coinfection
Liver stiffness
PBMCs
RNA-seq
Medicina
topic Advanced cirrhosis
Gene expression
HIV/HCV coinfection
Liver stiffness
PBMCs
RNA-seq
Medicina
description Background: Patients with advanced cirrhosis are at high risk of developing clinically significant portal hypertension (CSPH). We analyzed the gene expression profile of peripheral blood mononuclear cells (PBMCs) from HIV/HCV coinfected patients to identify a gene expression signature of advanced cirrhosis with high risk for CSPH. Methods: We conducted a cross-sectional study on 68 patients. Liver stiffness measurement (LSM) was used to stratify patients into < 12.5 kPa (no cirrhosis, n = 19), 12.5 – 24.9 kPa (cirrhosis, n = 20), and ≥ 25 kPa (advanced cirrhosis with high risk for CSPH, n = 29). Besides, we further evaluated LSM < 25 kPa (n = 39) vs. ≥ 25 kPa (n = 29). Total RNA was extracted from PBMCs, and poly(A) RNA sequencing was performed. Two significant differentially expressed (SDE) transcripts were validated by quantitative PCR in a different cohort (n = 46). Results: We found 60 SDE transcripts between patients with LSM < 12.5 kPa and ≥ 25 kPa. Partial least squares discriminant analysis showed that those 60 SDE transcripts collectively discriminated LSM ≥ 25 kPa, with an area under the receiver operating characteristic curve (AUROC) of 0.84. Eight genes had an AUROC ≥ 0.75 for LSM ≥ 25 kPa: five were positively associated with LSM values (SCAMP1, ABHD17B, GPR146, GTF2A1, and TMEM64), while three were inversely associated (ZFHX2-AS1, MDK, and STAG3L2). We validated the two SDE transcripts with the highest discrimination capacity in a different cohort, finding significant differences between < 25 kPa and ≥ 25 kPa (MDK (p = 0.006) and STAG3L2 (p = 0.021)). Conclusions: A gene expression signature of 60 transcripts was associated with advanced cirrhosis with high risk for CSPH in HIV/HCV coinfected patients
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-09
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/709802
https://dx.doi.org/10.1016/j.biopha.2023.114220
url http://hdl.handle.net/10486/709802
https://dx.doi.org/10.1016/j.biopha.2023.114220
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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