Academic Journal
PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study
| العنوان: | PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study |
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| المؤلفون: | Sergio Salgüero, Óscar Brochado-Kith, Ana Virseda Verdices, Juan Berenguer, Juan González-García, Isidoro Martínez, Cristina Díez, Víctor Hontañón, Leire Pérez-Latorre, Amanda Fernández-Rodríguez, María Ángeles Jiménez-Sousa, Salvador Resino |
| المصدر: | Biomedicine & Pharmacotherapy, Vol 159, Iss , Pp 114220- (2023) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2023 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | HIV/HCV coinfection, Gene expression, RNA-seq, PBMCs, Liver stiffness, Advanced cirrhosis, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0753-3322 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S0753332223000082; https://doaj.org/toc/0753-3322; https://doaj.org/article/6cd778fc60cd46bab421780bc1a73a4a |
| DOI: | 10.1016/j.biopha.2023.114220 |
| الاتاحة: | https://doi.org/10.1016/j.biopha.2023.114220 https://doaj.org/article/6cd778fc60cd46bab421780bc1a73a4a |
| رقم الانضمام: | edsbas.1BEDB620 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 07533322 |
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| DOI: | 10.1016/j.biopha.2023.114220 |