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Cellular and Molecular Neurobiology Nov 2023Liquid biopsy research on Low-Grade gliomas (LGG) has remained less conspicuous than that on other malignant brain tumors. Reliable serum markers would be precious for... (Review)
Review
Liquid biopsy research on Low-Grade gliomas (LGG) has remained less conspicuous than that on other malignant brain tumors. Reliable serum markers would be precious for diagnosis, follow- up and treatment. We propose a clinical utility score (CUS) for biomarkers in LGG that mirrors their clinical usefulness. We conducted a PRISMA review. We examined each biomarker classifying them by CUS and Level of Evidence (LOE). We identified four classes of biomarkers: (1). Circulating protein-(a) vitronectin discriminates LGG from HGG (Sn:98%, Sp:91%, CUS: 3, LOE: III), (b) CTLA-4 discriminates LGG from HGG, (cutoff: 220.43 pg/ml, Sn: 82%, Sp: 78%, CUS:3, LOE:III), (c) pre-operative TGF b1 predict astrocytoma (cutoff: 2.52 ng/ml, Sn: 94.9%, Sp: 100%, CUS:3, LOE:VI). (2). micro-RNA (miR)-(a) miR-16 discriminates between WHO IV and WHO II and III groups (AUC = 0.98, CUS:3, LOE: III), (b) miR-454-3p is higher in HGG than in LGG (p = 0.013, CUS:3, LOE: III), (c) miR-210 expression is related to WHO grades (Sn 83.2%, Sp 94.3%, CUS: 3, LOE: III). (3). Circulating DNA-(a) IDH1R132H mutation detected in plasma by combined COLD and digital PCR (Sn: 60%, Sp: 100%, CUS: 3, LOE: III). 4. Exosomes-(a) SDC1 serum levels could discriminate GBM from LGG (Sn: 71%, Sp: 91%, CUS: 2C, LOE: VI). Our investigation showed that miRs appear to have the highest clinical utility. The LOE of the studies assessed is generally low. A combined approach between different biomarkers and traditional diagnostics may be considered. We identified four main classes of biomarkers produced by LGG. We examined each biomarker, classifying them by clinical utility score (CUS) and level of evidence (LOE). Micro-RNA (miRs) appears to have the highest CUS and LOE.
Topics: Humans; Glioma; Brain Neoplasms; Biomarkers, Tumor; Liquid Biopsy; MicroRNAs; Neoplasm Grading
PubMed: 37704931
DOI: 10.1007/s10571-023-01406-9 -
Pulmonology Feb 2024Asbestos is still the leading cause of occupational cancer mortality worldwide. Asbestos-related lung cancer (LC) and malignant pleural mesothelioma (MPM) prognosis is... (Review)
Review
BACKGROUND
Asbestos is still the leading cause of occupational cancer mortality worldwide. Asbestos-related lung cancer (LC) and malignant pleural mesothelioma (MPM) prognosis is still poor especially at advanced stage, so early diagnosis biomarkers are needed. MicroRNAs (miRNAs) have been proposed as potential early diagnostic biomarkers of asbestos-related LC and MPM.
AIM
To evaluate the role of miRNAs as diagnostic and prognostic biomarkers of asbestos-related LC and MPM by performing a literature systematic review and meta-analysis.
METHODS
MEDLINE, EMBASE via Ovid, PUBMED and Cochrane library databases were systematically searched up to April 2023 to identify relevant articles. A grey literature search was also conducted using the Google Scholar platform. MeSH and free text terms for 'asbestos', 'occupational exposure', 'lung cancer', 'mesothelioma' and 'miRNAs' were used to search the literature. Our systematic review protocol was registered in the PROSPERO database. Study quality was assessed via the Newcastle-Ottawa Scale.
RESULTS
From the search, 331 articles were retrieved, and, after applying our selection criteria, and exclusion of one study for poor quality, 27 studies were included in the review. Most of the studies were hospital-based case-control, conducted in Europe, and evaluated MPM among men only. MiRNAs expression was measured mainly in plasma or serum. MiR-126, miR-132-3p, and miR-103a-3p were the most promising diagnostic biomarkers for MPM, and we estimated a pooled area under the curve (AUC) of 85 %, 73 %, and 50 %, respectively. In relation to MPM prognosis, miR-197‑3p resulted associated with increased survival time. MiR-126, alone and combined with miR-222, was confirmed associated also to LC diagnosis, together with miR-1254 and miR-574-5p; no miRNA was found associated to LC prognosis.
CONCLUSION
Based on our systematic literature review there is suggestive evidence that the expression of specific miRNAs in the blood serum or plasma are associated with asbestos-related LC and MPM diagnosis and prognosis. Further large longitudinal studies are urgently needed to validate these findings and elucidate the underlying mechanisms given the potential important implications for patients' survival.
PubMed: 38402124
DOI: 10.1016/j.pulmoe.2024.02.002 -
Frontiers in Oncology 2023Research on hepatocellular carcinoma (HCC) has grown significantly, and researchers cannot access the vast amount of literature. This study aimed to explore the research... (Review)
Review
INTRODUCTION
Research on hepatocellular carcinoma (HCC) has grown significantly, and researchers cannot access the vast amount of literature. This study aimed to explore the research progress in studying HCC over the past 30 years using a machine learning-based bibliometric analysis and to suggest future research directions.
METHODS
Comprehensive research was conducted between 1991 and 2020 in the public version of the PubMed database using the MeSH term "hepatocellular carcinoma." The complete records of the collected results were downloaded in Extensible Markup Language format, and the metadata of each publication, such as the publication year, the type of research, the corresponding author's country, the title, the abstract, and the MeSH terms, were analyzed. We adopted a latent Dirichlet allocation topic modeling method on the Python platform to analyze the research topics of the scientific publications.
RESULTS
In the last 30 years, there has been significant and constant growth in the annual publications about HCC (annual percentage growth rate: 7.34%). Overall, 62,856 articles related to HCC from the past 30 years were searched and finally included in this study. Among the diagnosis-related terms, "Liver Cirrhosis" was the most studied. However, in the 2010s, "Biomarkers, Tumor" began to outpace "Liver Cirrhosis." Regarding the treatment-related MeSH terms, "Hepatectomy" was the most studied; however, recent studies related to "Antineoplastic Agents" showed a tendency to supersede hepatectomy. Regarding basic research, the study of "Cell Lines, Tumors,'' appeared after 2000 and has been the most studied among these terms.
CONCLUSION
This was the first machine learning-based bibliometric study to analyze more than 60,000 publications about HCC over the past 30 years. Despite significant efforts in analyzing the literature on basic research, its connection with the clinical field is still lacking. Therefore, more efforts are needed to convert and apply basic research results to clinical treatment. Additionally, it was found that microRNAs have potential as diagnostic and therapeutic targets for HCC.
PubMed: 37664017
DOI: 10.3389/fonc.2023.1227991 -
BMC Cardiovascular Disorders Jun 2024Stent restenosis is a relatively common phenomenon among patients with coronary heart disease undergoing percutaneous coronary intervention (PCI). It seems that a set of...
BACKGROUND
Stent restenosis is a relatively common phenomenon among patients with coronary heart disease undergoing percutaneous coronary intervention (PCI). It seems that a set of clinical, laboratory, and even genetic factors make people susceptible to such a phenomenon and in fact, this is multi-factorial. We aimed to first determine the underlying clinical and laboratory risk factors for the occurrence of stent re-stenosis after PCI based on a systematic review study, and after that, through a bioinformatics study, to evaluate the related genes and microRNAs with the occurrence of stent re-stenosis.
MAIN TEXT
In the first step, the manuscript databases including Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane were deeply searched by the two blinded investigators for all eligible studies based on the considered keywords to introduce clinical and laboratory determinants of stent re-stenosis. In the bioinformatic phase, and following a review of the literature to identify genes and microRNAs involved in restenosis, the interaction of each gene with other genes associated with stent re-stenosis was determined by GeneMANIA network analysis and Cytoscape software. Overall, 67 articles (including 40,789 patients) on clinical and biochemical predictors for stent restenosis and 25 articles on genetic determinants of this event were eligible for the final analysis. The predictors for this event were categorized into four subgroups patient-based parameters including traditional cardiovascular risk profiles, stent-based parameters including type and diametric characteristics of the stents used, coronary lesion-based parameters including several two target lesions and coronary involvement severity and laboratory-based parameters particularly related to activation of inflammatory processes. In the bioinformatic phase, we uncovered 42 genes that have been described to be involved in such a phenomenon considering a special position for genes encoding inflammatory cytokines. Also, 12 microRNAs have been pointed to be involved in targeting genes involved in stent re-stenosis.
CONCLUSIONS
The incidence of stent re-stenosis will be the result of a complex interaction of clinical risk factors, laboratory factors mostly related to the activation of inflammatory processes, and a complex network of gene-to-gene interactions.
Topics: Humans; Percutaneous Coronary Intervention; Coronary Restenosis; Stents; Risk Factors; Computational Biology; Coronary Artery Disease; MicroRNAs; Risk Assessment; Genetic Predisposition to Disease; Treatment Outcome; Female; Male; Gene Regulatory Networks; Middle Aged; Aged
PubMed: 38877398
DOI: 10.1186/s12872-024-03955-3 -
Frontiers in Neurology 2024Brain neoplasms and central nervous system (CNS) disorders, particularly gliomas, have shown a notable increase in incidence over the last three decades, posing...
INTRODUCTION
Brain neoplasms and central nervous system (CNS) disorders, particularly gliomas, have shown a notable increase in incidence over the last three decades, posing significant diagnostic and therapeutic challenges. MicroRNAs (miRNAs) have emerged as promising biomarkers due to their regulatory role in gene expression, offering potential enhancements in glioma diagnosis and prognosis.
METHODS
This systematic review and meta-analysis, adhering to PRISMA guidelines, included 25 studies for diagnostic accuracy and 99 for prognostic analysis, published until August 27th, 2023. Studies were identified through comprehensive searches of PubMed, Web of Science, and Scopus databases. Inclusion criteria encompassed peer-reviewed original research providing sensitivity, specificity, and area under the curve (AUC) for miRNAs in glioma diagnosis, as well as survival outcomes with hazard ratios (HRs) or mean survival.
RESULTS AND DISCUSSION
Meta-analysis demonstrated miRNAs' high diagnostic accuracy, with a pooled sensitivity of 0.821 (95% CI: 0.781-0.855) and specificity of 0.831 (95% CI: 0.792-0.865), yielding an AUC of 0.893. Subgroup analysis by specimen type revealed consistent accuracy across blood, cerebrospinal fluid (CSF), and tissue samples. Our results also showed miRNAs can be potential prognostic biomarkers. miRNAs showed significant associations with overall survival (OS) (pooled HR: 2.0221; 95% CI: 1.8497-2.2105), progression-free survival (PFS) (pooled HR: 2.4248; 95% CI: 1.8888-3.1128), and disease-free survival (DFS) (pooled HR: 1.8973; 95% CI: 1.1637-3.0933) in tissue specimens. These findings underscore miRNAs' potential as valuable biomarkers for improving glioma diagnosis and prognosis, offering insights for enhancing clinical decision-making and patient outcomes.
PubMed: 38487328
DOI: 10.3389/fneur.2024.1357321 -
International Journal of Molecular... May 2024Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Given its prevalence, reliable biomarkers for early diagnosis are required.... (Meta-Analysis)
Meta-Analysis Review
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Given its prevalence, reliable biomarkers for early diagnosis are required. Exosomal proteins within extracellular nanovesicles are promising candidates for diagnostic, screening, prognostic, and disease monitoring purposes in neurological diseases such as PD. This review aims to evaluate the potential of extracellular vesicle proteins or miRNAs as biomarkers for PD. A comprehensive literature search until January 2024 was conducted across multiple databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, to identify relevant studies reporting exosome biomarkers in blood samples from PD patients. Out of 417 articles screened, 47 studies were selected for analysis. Among exosomal protein biomarkers, α-synuclein, tau, Amyloid β 1-42, and C-X-C motif chemokine ligand 12 (CXCL12) were identified as significant markers for PD. Concerning miRNA biomarkers, miRNA-24, miR-23b-3p, miR-195-3p, miR-29c, and mir-331-5p are promising across studies. α-synuclein exhibited increased levels in PD patients compared to control groups in twenty-one studies, while a decrease was observed in three studies. Our meta-analysis revealed a significant difference in total exosomal α-synuclein levels between PD patients and healthy controls (standardized mean difference [SMD] = 1.369, 95% confidence interval [CI] = 0.893 to 1.846, < 0.001), although these results are limited by data availability. Furthermore, α-synuclein levels significantly differ between PD patients and healthy controls (SMD = 1.471, 95% CI = 0.941 to 2.002, < 0.001). In conclusion, certain exosomal proteins and multiple miRNAs could serve as potential biomarkers for diagnosis, prognosis prediction, and assessment of disease progression in PD.
Topics: Humans; Parkinson Disease; Exosomes; Biomarkers; MicroRNAs; alpha-Synuclein; Amyloid beta-Peptides
PubMed: 38791346
DOI: 10.3390/ijms25105307 -
BMC Geriatrics Nov 2023Delirium is a prevalent neuropsychiatric medical phenomenon that causes serious emergency outcomes, including mortality and morbidity. It also increases the suffering...
Exploration of key drug target proteins highlighting their related regulatory molecules, functional pathways and drug candidates associated with delirium: evidence from meta-data analyses.
BACKGROUND
Delirium is a prevalent neuropsychiatric medical phenomenon that causes serious emergency outcomes, including mortality and morbidity. It also increases the suffering and the economic burden for families and carers. Unfortunately, the pathophysiology of delirium is still unknown, which is a major obstacle to therapeutic development. The modern network-based system biology and multi-omics analysis approach has been widely used to recover the key drug target biomolecules and signaling pathways associated with disease pathophysiology. This study aimed to identify the major drug target hub-proteins associated with delirium, their regulatory molecules with functional pathways, and repurposable drug candidates for delirium treatment.
METHODS
We used a comprehensive proteomic seed dataset derived from a systematic literature review and the Comparative Toxicogenomics Database (CTD). An integrated multi-omics network-based bioinformatics approach was utilized in this study. The STRING database was used to construct the protein-protein interaction (PPI) network. The gene set enrichment and signaling pathways analysis, the regulatory transcription factors and microRNAs were conducted using delirium-associated genes. Finally, hub-proteins associated repurposable drugs were retrieved from CMap database.
RESULTS
We have distinguished 11 drug targeted hub-proteins (MAPK1, MAPK3, TP53, JUN, STAT3, SRC, RELA, AKT1, MAPK14, HSP90AA1 and DLG4), 5 transcription factors (FOXC1, GATA2, YY1, TFAP2A and SREBF1) and 6 microRNA (miR-375, miR-17-5, miR-17-5p, miR-106a-5p, miR-125b-5p, and miR-125a-5p) associated with delirium. The functional enrichment and pathway analysis revealed the cytokines, inflammation, postoperative pain, oxidative stress-associated pathways, developmental biology, shigellosis and cellular senescence which are closely connected with delirium development and the hallmarks of aging. The hub-proteins associated computationally identified repurposable drugs were retrieved from database. The predicted drug molecules including aspirin, irbesartan, ephedrine-(racemic), nedocromil, and guanidine were characterized as anti-inflammatory, stimulating the central nervous system, neuroprotective medication based on the existing literatures. The drug molecules may play an important role for therapeutic development against delirium if they are investigated more extensively through clinical trials and various wet lab experiments.
CONCLUSION
This study could possibly help future research on investigating the delirium-associated therapeutic target biomarker hub-proteins and repurposed drug compounds. These results will also aid understanding of the molecular mechanisms that underlie the pathophysiology of delirium onset and molecular function.
Topics: Humans; Gene Regulatory Networks; Proteomics; MicroRNAs; Transcription Factors; Delirium
PubMed: 37993790
DOI: 10.1186/s12877-023-04457-1 -
Journal of Investigative Surgery : the... Dec 2023This study aims to investigate the association between miR-203 expression and the prognostic value in patients with esophageal cancer by the method of systematic review... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aims to investigate the association between miR-203 expression and the prognostic value in patients with esophageal cancer by the method of systematic review and meta-analysis.
METHODS
We searched PubMed, Web of Science, Embase, and Cochrane Library to collect studies on the relationship between miR-203 expression and the prognostic value of esophageal cancer up to July 2023. Stata 15.0 statistical software was used for data analysis. Hazard ratio (HR) and 95% confidence interval (CI) were used as effect sizes.
RESULTS
A total of 6 studies were included in this review, including 476 patients with esophageal cancer. The results showed that miR-203 low expression was associated with worse overall survival (OS) in patients with esophageal cancer compared with miR-203 high expression (HR = 2.80, 95%CI: 1.99 ∼ 3.93, < 0.001). The results of Egger's ( = 0.154) and Begg's Tests ( = 0.221) indicated no obvious publication bias. Sensitivity analysis verified the robustness of the results obtained in this study.
CONCLUSION
The expression of miR-203 is significantly correlated with the prognostic value in patients with esophageal cancer. Esophageal cancer patients with high expression of miR-203 had better prognosis than those with low expression of miR-203. Due to the limited studies included in this meta-analysis, more trials are needed to confirm the conclusions of this study in the future.
Topics: Humans; Prognosis; Esophageal Neoplasms; Biomarkers, Tumor; MicroRNAs
PubMed: 38047456
DOI: 10.1080/08941939.2023.2285780 -
Frontiers in Cellular Neuroscience 2023Limb-girdle muscular dystrophies (LGMD) constitute a heterogeneous group of neuromuscular disorders in which there are alterations in proteins responsible for the... (Review)
Review
Limb-girdle muscular dystrophies (LGMD) constitute a heterogeneous group of neuromuscular disorders in which there are alterations in proteins responsible for the preservation of muscle architecture and function, leading to proximal and progressive muscle weakness. There is, however, significant phenotypic and genotypic variation, as well as difficulty in establishing biomarkers that help to define pathogenic mechanisms and assess disease severity and progression. In this field, there is special attention to microRNAs, small non-coding RNA molecules related to the regulation of gene expression and, consequently, the production of proteins. Thus, this research aimed to verify the correlation between the expression of microRNAs and the severity, progression, and therapeutic response of LGMD animal models. A search was carried out in the PubMed, Embase, Scopus, ScienceDirect, Cochrane, and SciELO databases, with articles in English and without a time limit. The PRISMA 2020 checklist was used, and the protocol of this review was submitted to PROSPERO. The bibliographic survey of the 434 records found that 5 original articles met the inclusion criteria. The studies explored myomicroRNAs or miRNA panels with gene expression analysis. The analysis demonstrates that miR-1, 133a, and 206 are differentially expressed in serum and muscle. They change according to the degree of inflammation, fibrosis, muscle regeneration, and progression of the dystrophic process. MicroRNAs are up-regulated in dystrophic muscles, which are reversed after treatment in a dose-dependent manner. The present study inferred that miRs are essential in severity, progression, and therapeutic response in LGMD models and may be a useful biomarker in clinical research and prognosis. However, the practical application of these findings should be further explored.
PubMed: 38130868
DOI: 10.3389/fncel.2023.1233181 -
Oncology Letters Oct 2023The prognosis of a gastric cancer (GC) diagnosis is poor due to the current lack of effective early diagnostic methods. Extracellular vesicle (EV) biomarkers have...
The prognosis of a gastric cancer (GC) diagnosis is poor due to the current lack of effective early diagnostic methods. Extracellular vesicle (EV) biomarkers have previously demonstrated strong diagnostic efficiency for certain types of cancer, including pancreatic and lung cancer. The present review aimed to summarize the diagnostic value of circulating EV biomarkers for early stage GC. The PubMed, Medline and Web of Science databases were searched from May 1983 to September 18, 2022. All studies that reported the diagnostic performance of EV biomarkers for GC were included for analysis. Overall, 27 studies were selected containing 2,831 patients with GC and 2,117 controls. A total of 58 EV RNAs were reported in 26 studies, including 39 microRNAs (miRNAs), 10 long non-coding RNAs (lncRNAs), five circular RNAs, three PIWI-interacting RNAs and one mRNA, in addition to one protein in the remaining study. Meta-analysis of the aforementioned studies demonstrated that the pooled sensitivity, specificity and AUC value of the total RNAs were 84, 67% and 0.822, respectively. The diagnostic values of miRNAs were consistent with the total RNA, as the pooled sensitivity, specificity and AUC value were 84, 67% and 0.808, respectively. The pooled sensitivity, specificity and AUC values of lncRNAs were 89, 69% and 0.872, respectively, markedly higher compared with that of miRNAs. A total of five studies reported the diagnostic performance of EV RNA panels for early stage GC and reported powerful diagnostic values with a pooled sensitivity, specificity and AUC value of 80, 77% and 0.879, respectively. Circulating EV RNAs could have the potential to be used in the future as effective, noninvasive biomarkers for early GC diagnosis. Further research in this field is necessary to translate these findings into clinical practice.
PubMed: 37664665
DOI: 10.3892/ol.2023.14009