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Frontiers in Microbiology 2022The intersection between the human oral microbiome and oral health is an emerging area of study which has gained momentum over the last decade. This momentum has...
The intersection between the human oral microbiome and oral health is an emerging area of study which has gained momentum over the last decade. This momentum has motivated a search for associations between the oral microbiome and oral cancer, in hopes of identifying possible biomarkers that facilitate earlier diagnosis and improved prognosis for patients with that disease. The present study examined the relationship between the microbiome in the human oral cavity and oral squamous cell carcinoma (OSCC). We searched the literature for case-control studies which focused on the relationship between the human oral microbiome and OSCC. We aggregated three types of data from these studies: bacteriome data at the genus level, predicted functional pathway data, and gene abundance data. From these data, we noted several microbial genera which may be associated with oral cancer status, including . We also identified functional pathways which merit further investigation, including RNA degradation (ko03018) and primary immunodeficiency (ko05340). In addition, our analysis of gene abundance data identified the gene K06147 (ATP-binding cassette, subfamily B, bacterial) as being over abundant in OSCC samples. Our results are generalizations which identified some currents that we believe could guide further research. Our work faced several limitations related to the heterogeneity of the available data. Wide variation in methods for sample collection, methods for controlling for known behavioral risk factors, computing platform choice, and methods for case-control design all posed confounding factors in this work. We examined the current methods of data collection, data processing, and data reporting in order to offer suggestions toward the establishment of best practices within this field. We propose that these limitations should be addressed through the implementation of standardized data analytic practices that will conform to the rigor and reproducibility standards required of publicly funded research.
PubMed: 36338051
DOI: 10.3389/fmicb.2022.968304 -
European Journal of Cancer (Oxford,... Nov 2022Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review,... (Review)
Review
BACKGROUND
Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4.
METHODS
A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT, ATRX, TERT, and/or TP53.
RESULTS
The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2, high expression of RAD18, homozygous deletion of CDKN2A/B, amplification of PDGFRA, copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies.
CONCLUSIONS
Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; DNA; DNA-Binding Proteins; Homozygote; Humans; Isocitrate Dehydrogenase; Lymphoma, Follicular; MutS Homolog 2 Protein; Mutation; Phosphatidylinositol 3-Kinases; Sequence Deletion; TOR Serine-Threonine Kinases; Ubiquitin-Protein Ligases
PubMed: 36152406
DOI: 10.1016/j.ejca.2022.08.016 -
PLoS Medicine Aug 2022Accurate routine HIV viral load testing is essential for assessing the efficacy of antiretroviral treatment (ART) regimens and the emergence of drug resistance. While... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accurate routine HIV viral load testing is essential for assessing the efficacy of antiretroviral treatment (ART) regimens and the emergence of drug resistance. While the use of plasma specimens is the standard for viral load testing, its use is restricted by the limited ambient temperature stability of viral load biomarkers in whole blood and plasma during storage and transportation and the limited cold chain available between many health care facilities in resource-limited settings. Alternative specimen types and technologies, such as dried blood spots, may address these issues and increase access to viral load testing; however, their technical performance is unclear. To address this, we conducted a meta-analysis comparing viral load results from paired dried blood spot and plasma specimens analyzed with commonly used viral load testing technologies.
METHODS AND FINDINGS
Standard databases, conferences, and gray literature were searched in 2013 and 2018. Nearly all studies identified (60) were conducted between 2007 and 2018. Data from 40 of the 60 studies were included in the meta-analysis, which accounted for a total of 10,871 paired dried blood spot:plasma data points. We used random effects models to determine the bias, accuracy, precision, and misclassification for each viral load technology and to account for between-study variation. Dried blood spot specimens produced consistently higher mean viral loads across all technologies when compared to plasma specimens. However, when used to identify treatment failure, each technology compared best to plasma at a threshold of 1,000 copies/ml, the present World Health Organization recommended treatment failure threshold. Some heterogeneity existed between technologies; however, 5 technologies had a sensitivity greater than 95%. Furthermore, 5 technologies had a specificity greater than 85% yet 2 technologies had a specificity less than 60% using a treatment failure threshold of 1,000 copies/ml. The study's main limitation was the direct applicability of findings as nearly all studies to date used dried blood spot samples prepared in laboratories using precision pipetting that resulted in consistent input volumes.
CONCLUSIONS
This analysis provides evidence to support the implementation and scale-up of dried blood spot specimens for viral load testing using the same 1,000 copies/ml treatment failure threshold as used with plasma specimens. This may support improved access to viral load testing in resource-limited settings lacking the required infrastructure and cold chain storage for testing with plasma specimens.
Topics: Dried Blood Spot Testing; HIV Infections; HIV-1; Humans; RNA, Viral; Sensitivity and Specificity; Viral Load
PubMed: 35994520
DOI: 10.1371/journal.pmed.1004076 -
Frontiers in Genetics 2022Epigenomics has become a significant research interest at a time when rapid environmental changes are occurring. Epigenetic mechanisms mainly result from systems like...
Epigenomics has become a significant research interest at a time when rapid environmental changes are occurring. Epigenetic mechanisms mainly result from systems like DNA methylation, histone modification, and RNA interference. Epigenetic mechanisms are gaining importance in classical genetics, developmental biology, molecular biology, cancer biology, epidemiology, and evolution. Epigenetic mechanisms play important role in the action and interaction of plant genes during development, and also have an impact on classical plant breeding programs, inclusive of novel variation, single plant heritability, hybrid vigor, plant-environment interactions, stress tolerance, and performance stability. The epigenetics and epigenomics may be significant for crop adaptability and pliability to ambient alterations, directing to the creation of stout climate-resilient elegant crop cultivars. In this review, we have summarized recent progress made in understanding the epigenetic mechanisms in plant responses to biotic and abiotic stresses and have also tried to provide the ways for the efficient utilization of epigenomic mechanisms in developing climate-resilient crop cultivars, especially in chickpea, and other legume crops.
PubMed: 35937986
DOI: 10.3389/fgene.2022.900253 -
Ageing Research Reviews Nov 2022Modifications of RNA, collectively called the "epitranscriptome", might provide novel biomarkers and innovative targets for interventions in geroscience but are just... (Review)
Review
Modifications of RNA, collectively called the "epitranscriptome", might provide novel biomarkers and innovative targets for interventions in geroscience but are just beginning to be studied in the context of ageing and stress resistance. RNA modifications modulate gene expression by affecting translation initiation and speed, miRNA binding, RNA stability, and RNA degradation. Nonetheless, the precise underlying molecular mechanisms and physiological consequences of most alterations of the epitranscriptome are still only poorly understood. We here systematically review different types of modifications of rRNA, tRNA and mRNA, the methodology to analyze them, current challenges in the field, and human disease associations. Furthermore, we compiled evidence for a connection between individual enzymes, which install RNA modifications, and lifespan in yeast, worm and fly. We also included resistance to different stressors and competitive fitness as search criteria for genes potentially relevant to ageing. Promising candidates identified by this approach include RCM1/NSUN5, RRP8, and F33A8.4/ZCCHC4 that introduce base methylations in rRNA, the methyltransferases DNMT2 and TRM9/ALKBH8, as well as factors involved in the thiolation or A to I editing in tRNA, and finally the mA machinery for mRNA.
Topics: Aging; AlkB Homolog 8, tRNA Methyltransferase; Animals; Humans; Methyltransferases; MicroRNAs; RNA, Messenger; RNA, Ribosomal; RNA, Transfer; Saccharomyces cerevisiae
PubMed: 35908668
DOI: 10.1016/j.arr.2022.101700 -
Cancer Medicine Jan 2023Recently, serum exosomal circular RNAs (circRNAs) were applied to discriminate cancer patients from healthy individuals, indicating that exosomal circRNAs have the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recently, serum exosomal circular RNAs (circRNAs) were applied to discriminate cancer patients from healthy individuals, indicating that exosomal circRNAs have the potential to be novel biomarkers for cancer diagnosis. This study aims to summarize the role of exosomal circRNAs in cancer diagnosis by a meta-analysis.
METHODS
A comprehensive literature search was conducted up to July 2021 in PubMed, Web of Science, EMBASE, and Cochrane Database. To evaluate the diagnostic value, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled. Threshold effect followed by subgroup analysis and meta-regression were performed to explore the source of heterogeneity. Sensitivity analysis was performed to assess the stability of this meta-analysis model. Fagan plots and likelihood ratio scattergrams were used to explore the potential clinical significance.
RESULTS
Ten eligible studies with 514 controls and 557 patients were included in this diagnostic meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.75 (95% CI: 0.65-0.83), 0.84 (95% CI, 0.78-0.89), 5.87 (95% CI, 3.67-9.38), 0.28 (95% CI, 0.19-0.40), and 21.15 (95% CI, 10.25-43.68), respectively. The AUC was 0.89 (95% CI, 0.86-0.91). Sensitivity analysis showed that four studies had an impact on the pooled results and mainly contributed to the heterogeneity. Fagan's nomogram revealed that the prior probability of 20%, the post probability positive, the post probability negative were 59% and 6%, respectively.
CONCLUSION
Our results suggested that exosomal circRNAs might serve as powerful biomarkers in detecting cancers with high sensitivity and specificity. However, more well-designed and multicenter diagnostic tests are needed to validate our results.
Topics: Humans; RNA, Circular; Biomarkers, Tumor; Neoplasms; Multicenter Studies as Topic
PubMed: 35879835
DOI: 10.1002/cam4.5012 -
Journal of Clinical Laboratory Analysis Aug 2022Non-coding RNAs (ncRNAs) are involved in neuropathic pain development. Herein, we systematically searched for neuropathic pain-related ncRNAs expression changes,... (Review)
Review
BACKGROUND
Non-coding RNAs (ncRNAs) are involved in neuropathic pain development. Herein, we systematically searched for neuropathic pain-related ncRNAs expression changes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular non-coding RNAs (circRNAs).
METHODS
We searched two databases, PubMed and GeenMedical, for relevant studies.
RESULTS
Peripheral nerve injury or noxious stimuli can induce extensive changes in the expression of ncRNAs. For example, higher serum miR-132-3p, -146b-5p, and -384 was observed in neuropathic pain patients. Either sciatic nerve ligation, dorsal root ganglion (DRG) transaction, or ventral root transection (VRT) could upregulate miR-21 and miR-31 while downregulating miR-668 and miR-672 in the injured DRG. lncRNAs, such as early growth response 2-antisense-RNA (Egr2-AS-RNA) and Kcna2-AS-RNA, were upregulated in Schwann cells and inflicted DRG after nerve injury, respectively. Dysregulated circRNA homeodomain-interacting protein kinase 3 (circHIPK3) in serum and the DRG, abnormally expressed lncRNAs X-inactive specific transcript (XIST), nuclear enriched abundant transcript 1 (NEAT1), small nucleolar RNA host gene 1 (SNHG1), as well as ciRS-7, zinc finger protein 609 (cirZNF609), circ_0005075, and circAnks1a in the spinal cord were suggested to participate in neuropathic pain development. Dysregulated miRNAs contribute to neuropathic pain via neuroinflammation, autophagy, abnormal ion channel expression, regulating pain-related mediators, protein kinases, structural proteins, neurotransmission excitatory-inhibitory imbalances, or exosome miRNA-mediated neuron-glia communication. In addition, lncRNAs and circRNAs are essential in neuropathic pain by acting as antisense RNA and miRNA sponges, epigenetically regulating pain-related molecules expression, or modulating miRNA processing.
CONCLUSIONS
Numerous dysregulated ncRNAs have been suggested to participate in neuropathic pain development. However, there is much work to be done before ncRNA-based analgesics can be clinically used for various reasons such as conservation among species, proper delivery, stability, and off-target effects.
Topics: Ganglia, Spinal; Humans; MicroRNAs; Neuralgia; RNA, Circular; RNA, Long Noncoding
PubMed: 35808924
DOI: 10.1002/jcla.24592 -
Biomolecules Mar 2022RNA editing contributes to transcriptome diversification through RNA modifications in relation to genome-encoded information (RNA-DNA differences, RDDs). The deamination... (Review)
Review
RNA editing contributes to transcriptome diversification through RNA modifications in relation to genome-encoded information (RNA-DNA differences, RDDs). The deamination of Adenosine (A) to Inosine (I) or Cytidine (C) to Uridine (U) is the most common type of mammalian RNA editing. It occurs as a nuclear co- and/or post-transcriptional event catalyzed by ADARs (Adenosine deaminases acting on RNA) and APOBECs (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like genes). RNA editing may modify the structure, stability, and processing of a transcript. This review focuses on RNA editing in psychiatric, neurological, neurodegenerative (NDs), and autoimmune brain disorders in humans and rodent models. We discuss targeted studies that focus on RNA editing in specific neuron-enriched transcripts with well-established functions in neuronal activity, and transcriptome-wide studies, enabled by recent technological advances. We provide comparative editome analyses between human disease and corresponding animal models. Data suggest RNA editing to be an emerging mechanism in disease development, displaying common and disease-specific patterns. Commonly edited RNAs represent potential disease-associated targets for therapeutic and diagnostic values. Currently available data are primarily descriptive, calling for additional research to expand global editing profiles and to provide disease mechanistic insights. The potential use of RNA editing events as disease biomarkers and available tools for RNA editing identification, classification, ranking, and functional characterization that are being developed will enable comprehensive analyses for a better understanding of disease(s) pathogenesis and potential cures.
Topics: Adenosine; Adenosine Deaminase; Animals; Brain; Brain Diseases; Mammals; Neurodegenerative Diseases; RNA; RNA Editing
PubMed: 35327657
DOI: 10.3390/biom12030465 -
Translational Cancer Research Dec 2021To evaluate the clinical value of microRNA (miR) and circulating tumor RNA (ctDNA) in the diagnosis of epithelial ovarian cancer (EOC) by meta-analysis and indirect...
BACKGROUND
To evaluate the clinical value of microRNA (miR) and circulating tumor RNA (ctDNA) in the diagnosis of epithelial ovarian cancer (EOC) by meta-analysis and indirect comparison based on common reference criteria.
METHODS
The PubMed, EMBASE, MEDLINE, Cochrane Library, Chinese biology medicine (CBM), China national knowledge infrastructure (CNKI), Wanfang, and Chinese Weipu (VIP) databases were searched by computer. The retrieval time limit was from the date of establishment of the database to September 2020. Two researchers independently screened the literature and extracted the basic data according to the inclusion and exclusion criteria formulated in advance, and evaluated the literature quality according to the quality assessment of diagnostic accuracy research (quadas-2). The Meta disc 1.4 and Stata 12.0 software programs were used for meta-analysis to calculate the combined sensitivity, combined specificity, combined positive likelihood ratio, combined negative likelihood ratio and combined diagnostic odds ratio (DOR). The summary receiver operating characteristic (SROC) curve was drawn using Revman 5.3 software, and the stability of the results was evaluated by sensitivity analysis. The publication bias was evaluated by Deek's funnel asymmetric test. The relative diagnostic odds ratio (RDOR) results of indirect comparison between microRNA and ctDNA were obtained using R software.
RESULTS
Nineteen articles were included, including a total of 1,351 EOC patients and 1,194 controls. The heterogeneity test showed that there was obvious heterogeneity caused by non-threshold effect. The random effects model was used for meta-analysis of microRNA in the diagnosis of EOC. The results showed that there was no significant difference between microRNA and ctDNA in the accuracy of EOC diagnosis. The asymmetric test of Deek's funnel chart showed that there was no significant publication bias.
DISCUSSION
There are some limitations in this study, there is no blind diagnostic test, and the intensity of indirect comparison evidence is lower than that of direct comparison evidence. The accuracy of diagnostic tests and the imperfection of mesh meta-analysis statistical methods. MicroRNA and ctDNA have similar clinical diagnostic value for EOC.
PubMed: 35116384
DOI: 10.21037/tcr-21-2609 -
Frontiers in Oncology 2021Liquid biopsy includes non-invasive analysis of circulating tumor-derived substances. It is a novel, innovative cancer screening tool that overcomes the limitations of...
Liquid biopsy includes non-invasive analysis of circulating tumor-derived substances. It is a novel, innovative cancer screening tool that overcomes the limitations of current invasive tissue examinations in precision oncology. Circular RNA (circRNA) is a recent, novel, and attractive liquid biomarker showing stability, abundance, and high specificity in various diseases, especially in human cancers. This review focused on the emerging potential of human circRNA in body fluids as the liquid biopsy biomarkers for cancers and the methods used to detect the circRNA expression and summarized the construction of circRNA biomarkers in body fluids for treating human cancers and their limitations before they become part of routine clinical medicine. Furthermore, the future opportunities and challenges of translating circRNAs in liquid biopsy into clinical practices were explored.
PubMed: 34722285
DOI: 10.3389/fonc.2021.736546