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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 -
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 -
Medicine Nov 2023Lung cancer is the leading cause of death worldwide, and its diagnosis remains a significant challenge. Identifying effective methods to differentiate benign from... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lung cancer is the leading cause of death worldwide, and its diagnosis remains a significant challenge. Identifying effective methods to differentiate benign from malignant lung nodules is of paramount importance. This meta-analysis aimed to evaluate the clinical utility of circulating microRNAs (miRNAs) for the differential diagnosis of benign and malignant lung nodules.
METHODS
This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search was conducted across 4 electronic databases, without any temporal restrictions. The inclusion and exclusion criteria were strictly applied to assess the clinical applications of circulating miRNAs. A robust and transparent quality assessment was performed using the quality assessment of diagnostic accuracy studies-2 tool, and rigorous statistical analyses were conducted to synthesize the various diagnostic measures.
RESULTS
In the meta-analysis of 11 studies, quality assessment of diagnostic accuracy studies-2 assessment revealed < 5% high-risk methodologies, ensuring robustness. Sensitivity and Specificity were consolidated at 0.83 (95% confidence interval [CI]: 0.72-0.90) and 0.81 (95% CI: 0.73-0.88), respectively. The positive likelihood ratio and negative likelihood ratio were 4.45 (95% CI: 3.03-6.54) and 0.21 (95% CI: 0.12-0.35), respectively. The diagnostic odds ratio was 21.31 (95% CI: 10.25-44.30) and area under the receiver operating characteristic curve was 0.89 (95% CI: 0.86-0.91). Subgroup analysis highlighted significant variations in diagnostic accuracy by ethnicity and miRNA source, with non-Asian populations and serum-based tests showing higher diagnostic accuracy.
CONCLUSION
This meta-analysis demonstrated that circulating miRNAs hold substantial diagnostic value in distinguishing between benign and malignant lung nodules.
Topics: Humans; MicroRNAs; Sensitivity and Specificity; ROC Curve; Circulating MicroRNA; Lung
PubMed: 37986348
DOI: 10.1097/MD.0000000000035857 -
BMC Cancer Nov 2023RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb) therapy, but many tumors containing wild-type RAS genes still do not respond to these therapies. Some additional biomarkers may have prognostic or predictive roles, but conclusions remain controversial.
METHODS
We performed a meta-analysis and systematic review of randomized controlled trials comparing anti-EGFR mAb therapy with alternative therapy that investigated the prognostic and predictive impact of additional biomarkers in RAS wild-type (wt) mCRC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) for objective response rate (ORR) were calculated. The prognostic value of biomarkers was investigated by separately pooling HR and OR for different treatment groups in an individual study. The predictive value was assessed by pooling study interactions between treatment effects and biomarker subgroups.
RESULTS
Thirty publications reporting on eighteen trials were selected, including a total of 13,507 patients. In prognostic analysis, BRAF mutations were associated with poorer PFS [HRs = 3.76 (2.47-5.73) and 2.69 (1.82-3.98)] and OS [HRs = 2.66 (1.95-3.65) and 2.45 (1.55-3.88)] in both the experimental and control arms; low miR-31-3p expression appeared to have longer PFS and OS. In terms of predictive effect, a lack of response to anti-EGFR therapy was observed in patients with BRAF mutant tumors (P < 0.01 for PFS). Patients with tumors with any mutation in the KRAS/NRAS/BRAF/PIK3CA gene also showed similar results compared with all wild-type tumors (P for PFS, OS, and ORR were < 0.01, < 0.01 and 0.01, respectively). While low miR-31-3p expression could predict PFS (P = 0.01) and OS (P = 0.04) benefit. The prognostic and predictive value regarding PIK3CA mutations, PTEN mutations or deletions, EGFR, EREG/AREG, HER2, HER3, and HER4 expression remains uncertain.
CONCLUSIONS
In RAS wt mCRC patients receiving EGFR-targeted therapy, BRAF mutation is a powerful prognostic and therapy-predictive biomarker, with no effect found for PIK3CA mutation, PTEN mutation or deletion, but the combined biomarker KRAS/NRAS/BRAF/PIK3CA mutations predict resistance to anti-EGFR therapy. Low miR-31-3p expression may have positive prognostic and therapy predictive effects. Evidence on the prognostic and predictive roles of EGFR and its ligands, and HER2/3/4 is insufficient.
Topics: Humans; Prognosis; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Proto-Oncogene Proteins p21(ras); ErbB Receptors; Antibodies, Monoclonal; Colonic Neoplasms; Rectal Neoplasms; Biomarkers; Class I Phosphatidylinositol 3-Kinases; Mutation; MicroRNAs; Biomarkers, Tumor
PubMed: 37974093
DOI: 10.1186/s12885-023-11600-z -
Association of noncoding RNAs with Kawasaki disease: A meta-analysis based on the current evidences.Medicine Nov 2023In recent years, many studies have focused on the relationship between noncoding RNAs (ncRNAs) and Kawasaki disease (KD). Studies have indicated that ncRNAs are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In recent years, many studies have focused on the relationship between noncoding RNAs (ncRNAs) and Kawasaki disease (KD). Studies have indicated that ncRNAs are associated with the occurrence and development of KD. Thus, we performed a systematic review and meta-analysis to investigate the diagnostic value of ncRNAs in KD patients.
METHODS
We searched the PubMed, Web of Science, Embase and Cochrane Library, China National Knowledge Infrastructure, VIP, China Biology Medicine disc databases, and Wanfang databases until August 25, 2023 and screened all eligible studies focusing on the diagnostic performance of ncRNAs in KD patients.
RESULTS
In total, 535 articles were found, and 28 articles were included in this systematic review and meta-analysis. The calculated area under the curve value was 0.880 (95% confidence intervals, 0.840-0.900). The pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were 0.790, 0.830, 4.610, and 0.260, respectively. The pooled diagnostic odds ratio was 17.890 (95% confidence intervals, 13.110-24.420), indicating a relatively good diagnostic performance of the ncRNAs for detecting KD. In addition, the diagnostic value of micro RNAs in KD was better than that of long noncoding RNAs and circular noncoding RNAs. A subgroup analysis by specimen indicated a better diagnostic value of ncRNAs in plasma and platelet than serum. The diagnostic accuracy of ncRNAs was better in febrile controls than in healthy control groups, indicating a relatively good accuracy in distinguishing KD patients from febrile diseases.
CONCLUSIONS
This systematic review and meta-analysis demonstrated that ncRNAs could be used as novel biomarkers for detecting KD. More studies should be conducted in the future to verify the diagnostic values of ncRNAs in KD.
Topics: Humans; Mucocutaneous Lymph Node Syndrome; Sensitivity and Specificity; Biomarkers; MicroRNAs; RNA, Circular
PubMed: 37960719
DOI: 10.1097/MD.0000000000035736 -
International Journal of Molecular... Oct 2023Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer "theranostic" tools, with strong clinical relevance....
Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer "theranostic" tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further studies are still required to address this challenging issue. The present study examined the expression profiles of EV-packaged miRNAs to identify novel miRNA signatures in breast cancer and verified their diagnostic accuracy. Circulating EVs were isolated from healthy controls and breast cancer patients and characterized following the MISEV 2018 guidelines. RNA-sequencing and real-time PCR showed that miRNA-27a and miRNA-128 were significantly down-regulated in patient-derived EVs compared to controls in screening and validation cohorts. Bioinformatics analyses of miRNA-target genes indicated several enriched biological processes/pathways related to breast cancer. Receiver operating characteristic (ROC) curves highlighted the ability of these EV-miRNAs to distinguish breast cancer patients from non-cancer controls. According to other reports, the levels of EV-miRNA-27a and EV-miRNA-128 are not associated with their circulating ones. Finally, evidence from the studies included in our systematic review underscores how the expression of these miRNAs in biofluids is still underinvestigated. Our findings unraveled the role of serum EV-derived miRNA-27a and miRNA-128 in breast cancer, encouraging further investigation of these two miRNAs within EVs towards improved breast cancer detection.
Topics: Humans; Female; MicroRNAs; Breast Neoplasms; Extracellular Vesicles
PubMed: 37958677
DOI: 10.3390/ijms242115695 -
The British Journal of Nutrition Mar 2024Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of... (Review)
Review
Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of phytosterols/phytostanols reduces levels of circulating LDL-cholesterol, a causative biomarker of CVD, and is linked to a reduced risk of some cancers. Individuals who consume phytosterols/phytostanols in their diet may do so for many years as part of a non-pharmacological route to lower cholesterol or as part of a healthy diet. However, the impact of long term or high intakes of dietary phytosterols/phytostanols has not been on whole-body epigenetic changes before. The aim of this systematic review was to identify all publications that have evaluated changes to epigenetic mechanisms (post-translation modification of histones, DNA methylation and miRNA expression) in response to phytosterols/phytostanols. A systematic search was performed that returned 226 records, of which eleven were eligible for full-text analysis. Multiple phytosterols were found to inhibit expression of histone deacetylase (HDAC) enzymes and were also predicted to directly bind and impair HDAC activity. Phytosterols were found to inhibit the expression and activity of DNA methyl transferase enzyme 1 and reverse cancer-associated gene silencing. Finally, phytosterols have been shown to regulate over 200 miRNA, although only five of these were reported in multiple publications. Five tissue types (breast, prostate, macrophage, aortic epithelia and lung) were represented across the studies, and although phytosterols/phytostanols alter the molecular mechanisms of epigenetic inheritance in these mammalian cells, studies exploring meiotic or transgenerational inheritance were not found.
Topics: Male; Animals; Humans; Phytosterols; Noncommunicable Diseases; Cholesterol; Epigenesis, Genetic; Neoplasms; MicroRNAs; Mammals
PubMed: 37955052
DOI: 10.1017/S0007114523002532 -
Journal of Sport and Health Science May 2024Regular physical exercise has been recognized as a potent modulator of immune function, with its effects including enhanced immune surveillance, reduced inflammation,... (Review)
Review
Regular physical exercise has been recognized as a potent modulator of immune function, with its effects including enhanced immune surveillance, reduced inflammation, and improved overall health. While strong evidence exists that physical exercise affects the specific expression and activity of non-coding RNAs (ncRNAs) also involved in immune system regulation, heterogeneity in individual study designs and analyzed exercise protocols exists, and a condensed list of functional, exercise-dependent ncRNAs with known targets in the immune system is missing from the literature. A systematic review and qualitative analysis was used to identify and categorize ncRNAs participating in immune modulation by physical exercise. Two combined approaches were used: (a) a systematic literature search for "ncRNA and exercise immunology", (b) and a database search for microRNAs (miRNAs) (miRTarBase and DIANA-Tarbase v8) aligned with known target genes in the immune system based on the Reactome database, combined with a systematic literature search for "ncRNA and exercise". Literature searches were based on PubMed, Web of Science, and SPORTDiscus; and miRNA databases were filtered for targets validated by in vitro experimental data. Studies were eligible if they reported on exercise-based interventions in healthy humans. After duplicate removal, 95 studies were included reporting on 164 miRNAs, which were used for the qualitative synthesis. Six studies reporting on long-noncoding RNAs (lncRNAs) or circular RNAs were also identified. Results were analyzed using ordering tables that included exercise modality (endurance/resistance exercise), acute or chronic interventions, as well as the consistency in reported change between studies. Evaluation criteria were defined as "validated" with 100% of ≥3 independent studies showing identical direction of regulation, "plausible" (≥80%), or "suggestive" (≥70%). For resistance exercise, upregulation of miR-206 was validated while downregulation of miR-133a appeared plausible. For endurance exercise, 15 miRNAs were categorized as validated, with 12 miRNAs being consistently elevated and 3 miRNAs being downregulated, most of them after acute exercise training. In conclusion, our approach provides evidence that miRNAs play a major role in exercise-induced effects on the innate and adaptive immune system by targeting different pathways affecting immune cell distribution, function, and trafficking as well as production of (anti-)inflammatory cytokines. miRNAs miR-15, miR-29c, miR-30a, miR-142/3, miR-181a, and miR-338 emerged as key players in mediating the immunomodulatory effects of exercise predominantly after acute bouts of endurance exercise.
Topics: Humans; Exercise; MicroRNAs; RNA, Untranslated; Immune System
PubMed: 37925072
DOI: 10.1016/j.jshs.2023.11.001 -
International Journal of Molecular... Oct 2023Structural or post-traumatic epilepsy often develops after brain tissue damage caused by traumatic brain injury, stroke, infectious diseases of the brain, etc. Most... (Review)
Review
Structural or post-traumatic epilepsy often develops after brain tissue damage caused by traumatic brain injury, stroke, infectious diseases of the brain, etc. Most often, between the initiating event and epilepsy, there is a period without seizures-a latent period. At this time, the process of restructuring of neural networks begins, leading to the formation of epileptiform activity, called epileptogenesis. The prediction of the development of the epileptogenic process is currently an urgent and difficult task. MicroRNAs are inexpensive and minimally invasive biomarkers of biological and pathological processes. The aim of this study is to evaluate the predictive ability of microRNAs to detect the risk of epileptogenesis. In this study, we conducted a systematic search on the MDPI, PubMed, ScienceDirect, and Web of Science platforms. We analyzed publications that studied the aberrant expression of circulating microRNAs in epilepsy, traumatic brain injury, and ischemic stroke in order to search for microRNAs-potential biomarkers for predicting epileptogenesis. Thus, 31 manuscripts examining biomarkers of epilepsy, 19 manuscripts examining biomarkers of traumatic brain injury, and 48 manuscripts examining biomarkers of ischemic stroke based on circulating miRNAs were analyzed. Three miRNAs were studied: miR-21, miR-181a, and miR-155. The findings showed that miR-21 and miR-155 are associated with cell proliferation and apoptosis, and miR-181a is associated with protein modifications. These miRNAs are not strictly specific, but they are involved in processes that may be indirectly associated with epileptogenesis. Also, these microRNAs may be of interest when they are studied in a cohort with each other and with other microRNAs. To further study the microRNA-based biomarkers of epileptogenesis, many factors must be taken into account: the time of sampling, the type of biological fluid, and other nuances. Currently, there is a need for more in-depth and prolonged studies of epileptogenesis.
Topics: Humans; MicroRNAs; Epilepsy; Brain Injuries, Traumatic; Biomarkers; Circulating MicroRNA; Ischemic Stroke
PubMed: 37895044
DOI: 10.3390/ijms242015366 -
International Journal of Molecular... Oct 2023The analysis of circulating tumor cells and tumor-derived materials, such as circulating tumor DNA, circulating miRNAs (cfmiRNAs), and extracellular vehicles provides... (Review)
Review
The analysis of circulating tumor cells and tumor-derived materials, such as circulating tumor DNA, circulating miRNAs (cfmiRNAs), and extracellular vehicles provides crucial information in cancer research. CfmiRNAs, a group of short noncoding regulatory RNAs, have gained attention as diagnostic and prognostic biomarkers. This review focuses on the discovery phases of cfmiRNA studies in breast cancer patients, aiming to identify altered cfmiRNA levels compared to healthy controls. A systematic literature search was conducted, resulting in 16 eligible publications. The studies included a total of 585 breast cancer cases and 496 healthy controls, with diverse sample types and different cfmiRNA assay panels. Several cfmiRNAs, including MIR16, MIR191, MIR484, MIR106a, and MIR193b, showed differential expressions between breast cancer cases and healthy controls. However, the studies had a high risk of bias and lacked standardized protocols. The findings highlight the need for robust study designs, standardized procedures, and larger sample sizes in discovery phase studies. Furthermore, the identified cfmiRNAs can serve as potential candidates for further validation studies in different populations. Improving the design and implementation of cfmiRNA research in liquid biopsies may enhance their clinical diagnostic utility in breast cancer patients.
Topics: Humans; Female; MicroRNAs; Gene Expression Profiling; Biomarkers, Tumor; Breast Neoplasms; Neoplastic Cells, Circulating
PubMed: 37894794
DOI: 10.3390/ijms242015114