Banca de QUALIFICAÇÃO: HEMERSON CASADO GAMA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : HEMERSON CASADO GAMA
DATE: 02/05/2024
TIME: 14:00
LOCAL: Sala Virtual
TITLE:

Systematic review and meta-analysis of dysregulated microRNAs derived from liquid biopsies as biomarkers for amyotrophic lateral sclerosis

KEY WORDS:

ALS; miRNAs; biomarkers; liquid biopsies; dysregulated expression.

PAGES: 31
BIG AREA: Ciências Biológicas
AREA: Farmacologia
SUMMARY:

The discovery of disease-specific biomarkers, such as microRNAs (miRNAs), has the potential to transform the landscape of Amyotrophic Lateral Sclerosis (ALS) by facilitating timely diagnosis, monitoring treatment response, and accelerating drug discovery. This advancement will ultimately improve the quality of life and survival rate of ALS patients. Despite more than a decade of research, no miRNA biomarker candidate has been translated into the clinical practice. We conducted a systematic review and meta-analysis to quantitatively synthesize data from original studies that analyzed miRNA expression from liquid biopsies via PCR and compared them to healthy controls. The protocol for this study adhered to the PRISMA guidelines and its details are registered in the PROSPERO (CRD42021230232). We performed a comprehensive query search of PubMed, Embase, Web of Science, and Virtual Health Library databases, without language restrictions, and between the years 2000 and 2022. Our search retrieved 2412 studies, of which 1344 duplicates were eliminated. We applied our exclusion criteria (non-original studies, non-ALS studies, non-human studies, and non-miRNAs expression studies) to the remaining 1068 studies, resulting in the additional removal of 971 studies. After fulltext screening of the remaining 97 studies (our eligibility criteria: patient studies; biological fluids as source material; ALS versus healthy controls; PCR evaluation or validation of miRNA expression; and clear statistical analysis), we identified 31 as eligible for qualitative synthesis. Most studies focused on sporadic ALS (38.7%), used the El-Escorial, or its revised version, as diagnostic criteria (45.2%), included less than 30 patients (58.1%), and fewer than half of the studies reported on the age of disease onset (38.7%). Information on therapeutic treatment was largely absent, with only seven studies providing any form of information (22.6%). The primary source of tissue sampling was serum (38.7%), followed by extracellular vesicles (EVs) derived from different fluids (19.4%), cerebrospinal fluid (CSF; 12.9%), leukocytes (9, 7%), plasma (9.7%) and peripheral blood (3.2%). Only two studies analyzed multiple tissues, including serum and CSF (3.2%), and serum, CSF and leukocytes (3.2%). We analyzed data on 807 miRNA species from 31 studies and stratified them based on tissue source and direction of dysregulation (i.e.: up-, down-, or unregulated). We identified consistently dysregulated miRNAs in serum (hsa-miR-3665, -4530, -4745-5p, -206); blood (hsa-miR-338-3p, -183-5p); CFS (hsa-miR-34a-3p); plasma (hsa-miR-206); and neuralenriched extracellular vesicles from plasma (hsa-miR-146a-5p, -151a-5p, -10b-5p, -29b-3p, and -4454). The meta-analyses provided additional support for the upregulation of hsa-miR-206, hsa-miR-338-3p, hsa-miR-146a-5p and hsa-miR-151a-5p, and downregulation of hsa-miR-183-5p, hsa-miR-10b-5p, hsa-miR-29b-3p, and hsa-miR-4454 as consistent indicators of ALS across independent studies. Analysis of enriched pathways associated with consistently dysregulated miRNAs showed correlation with various processes and diseases, e.g., fatty acid biosynthesis and metabolism, and p53 and PI3-Akt signaling pathways. A discussion about the methodological variabilities and inconsistencies found in the expression of miRNAs in different studies is also presented. In conclusion, our results provide valuable insights into the current understanding of miRNAs’ dysregulated expression in ALS patients, contributing to the ongoing efforts towards discovering disease-specific biomarkers.

COMMITTEE MEMBERS:
Externo(a) à Instituição - DANILO ALVES PINTO NAGEM - UFRN
Presidente - 2033893 - MARCELO DUZZIONI
Interno(a) - 1974414 - OLAGIDE WAGNER DE CASTRO