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Medicine Feb 2023An increasing number of studies have shown the potential diagnostic value of cell-free DNA (cfDNA) as a new biomarker in the management of thyroid cancer (TC); however,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
An increasing number of studies have shown the potential diagnostic value of cell-free DNA (cfDNA) as a new biomarker in the management of thyroid cancer (TC); however, the accuracy of research results is inconsistent. This meta-analysis is the first to synthesize published results and evaluate the application value of circulating cfDNA in the diagnosis of TC.
METHODS
A search strategy was developed according to PICO (P: Patient; I: Intervention; C: Comparison; O: Outcome) principles. We searched 5 databases until October 2022. Original studies that examined cfDNA for the diagnosis of TC and used pathology as the gold standard were included in this meta-analysis. A random-effects model was used to pool the data extracted from individual studies, including the number of patients and the numbers of true positives, false positives, true negatives, and false negatives.
RESULTS
A total of 622 patients with TC, 547 patients with benign thyroid nodules, and 98 healthy individuals were included in 20 studies reported in 14 articles. The types of cfDNA included in the research include specific mutations of cfDNA, methylation of cfDNA, the content of cfDNA, and cfDNA index. After rigorous statistical analysis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 0.76 (95% confidence interval [CI] 0.62-0.85), 0.87 (95% CI 0.78-0.93), 5.08 (95% CI 3.3-10.3), 0.28 (95% CI 0.17-0.46), 21 (95% CI 9-49), and 0.89 (95% CI 0.86-0.91), respectively. The meta-regression results showed that the number of cfDNAs, cfDNA methylation status, and sample size were the sources of heterogeneity in the specificity of the study. A subgroup analysis showed that the quantitative analysis group (cfDNA level) had a higher diagnostic accuracy than that of the qualitative analysis group (cfDNA methylation, mutation, or integrity index), with a sensitivity of 0.84, specificity of 0.89, and area under the curve of 0.91.
CONCLUSIONS
The results of this meta-analysis suggest that cfDNA has value as an adjunct for the diagnosis of TC. Quantitative detection of cfDNA can achieve relatively high diagnostic accuracy. However, due to heterogeneity, the test results based on cfDNA for TC should be interpreted with caution.
Topics: Humans; Cell-Free Nucleic Acids; ROC Curve; Biomarkers, Tumor; Mutation; Thyroid Neoplasms; Sensitivity and Specificity
PubMed: 36800605
DOI: 10.1097/MD.0000000000032928 -
BMC Genomic Data Jan 2024In this study, we aim to investigate the association between BRCA1/2 mutation and uterine cancer incidence. (Meta-Analysis)
Meta-Analysis
PURPOSE
In this study, we aim to investigate the association between BRCA1/2 mutation and uterine cancer incidence.
MATERIAL AND METHOD
We systematically searched three databases including PubMed, Scopus, and Google Scholar up to August 2023; and reviewed 23 cohorts and cross-sectional studies to explore the association between BRCA1/2 mutations and uterine cancer incidence.
RESULTS
This systematic review comprised a total of 21 cohort studies and 2 cross-sectional studies after the screening process. According to meta-analysis the prevalence of the BRCA1/2 gene in patients with uterine cancer was 0.02 (95%CI = [0.01,0.03], P < 0.01, I = 94.82%) CONCLUSIONS: Our meta-analysis investigates a 2% prevalence of BRCA1/2 mutation in patients with uterine cancer. Patients with BRCA1/2 mutations might be more conscious of uterine malignancies.
Topics: Female; Humans; BRCA1 Protein; BRCA2 Protein; Cross-Sectional Studies; Mutation; Uterine Neoplasms
PubMed: 38297203
DOI: 10.1186/s12863-024-01189-y -
Asia-Pacific Journal of Ophthalmology... 2016Retinitis pigmentosa is the most common form of hereditary retinal degeneration causing blindness. Great progress has been made in the identification of the causative... (Review)
Review
Retinitis pigmentosa is the most common form of hereditary retinal degeneration causing blindness. Great progress has been made in the identification of the causative genes. Gene diagnosis will soon become an affordable routine clinical test because of the wide application of next-generation sequencing. Gene-based therapy provides hope for curing the disease. Investigation into the molecular pathways from mutation to rod cell death may reveal targets for developing new treatment. Related progress with existing systematic review is briefly summarized so that readers may find the relevant references for in-depth reading. Future trends in the study of retinitis pigmentosa are also discussed.
Topics: Animals; Clinical Trials as Topic; Cone-Rod Dystrophies; Disease Management; Disease Models, Animal; Gene Expression Profiling; Genetic Therapy; High-Throughput Nucleotide Sequencing; Humans; Mutation; Retinal Degeneration; Retinitis Pigmentosa; Stem Cell Transplantation
PubMed: 27488069
DOI: 10.1097/APO.0000000000000227 -
Scientific Reports Nov 2022Immune checkpoint inhibitors have been approved in the USA for tumours exhibiting mismatch repair deficiency (dMMR), microsatellite instability (MSI), or high tumour... (Meta-Analysis)
Meta-Analysis
Immune checkpoint inhibitors have been approved in the USA for tumours exhibiting mismatch repair deficiency (dMMR), microsatellite instability (MSI), or high tumour mutational burden (TMB), with regulatory and reimbursement applications in multiple other countries underway. As the estimated budget impacts of future reimbursements depend on the size of the potential target population, we performed a scoping review and meta-analysis of the prevalence of these pan-tumour biomarkers in different cancers. We systematically searched Medline/Embase and included studies reporting the prevalence of dMMR/MSI/high TMB in solid tumours published 01/01/2018-31/01/2021. Meta-analyses were performed separately for the pan-cancer prevalence of each biomarker, and by cancer type and stage where possible. The searches identified 3890 papers, with 433 prevalence estimates for 32 different cancer types from 201 studies included in meta-analyses. The pooled overall prevalence of dMMR, MSI and high TMB (≥ 10 mutations/Mb) in pan-cancer studies was 2.9%, 2.7% and 14.0%, respectively. The prevalence profiles of dMMR/MSI and high TMB differed across cancer types. For example, endometrial, colorectal, small bowel and gastric cancers showed high prevalence of both dMMR and MSI (range: 8.7-26.8% and 8.5-21.9%, respectively) and high TMB (range: 8.5-43.0%), while cervical, esophageal, bladder/urothelial, lung and skin cancers showed low prevalence of dMMR and MSI (< 5%), but high prevalence of high TMB (range: 23.7-52.6%). For other cancer types, prevalence of all three biomarkers was generally low (< 5%). This structured review of dMMR/MSI/high TMB prevalence across cancers and for specific cancer types and stages provide timely evidence to inform budget impact forecasts in health technology assessments for drug approvals based on these pan-tumour biomarkers.
Topics: Humans; Microsatellite Instability; Biomarkers, Tumor; Prevalence; Immune Checkpoint Inhibitors; Skin Neoplasms
PubMed: 36443366
DOI: 10.1038/s41598-022-23319-1 -
PloS One 2021Before anti-EGFR therapy is given to patients with colorectal cancer, it is required to determine KRAS mutation status in tumor. When tumor tissue is not available,... (Meta-Analysis)
Meta-Analysis
The diagnostic accuracy of digital PCR, ARMS and NGS for detecting KRAS mutation in cell-free DNA of patients with colorectal cancer: A systematic review and meta-analysis.
INTRODUCTION
Before anti-EGFR therapy is given to patients with colorectal cancer, it is required to determine KRAS mutation status in tumor. When tumor tissue is not available, cell-free DNA (liquid biopsy) is commonly used as an alternative. Due to the low abundance of tumor-derived DNA in cell-free DNA samples, methods with high sensitivity were preferred, including digital polymerase chain reaction, amplification refractory mutation system and next-generation sequencing. The aim of this systemic review and meta-analysis was to investigate the accuracy of those methods in detecting KRAS mutation in cell-free DNA sample from patients with colorectal cancer.
METHODS
Literature search was performed in Pubmed, Embase, and Cochrane Library. After removing duplicates from the 170 publications found by literature search, eligible studies were identified using pre-defined criteria. Quality of the publications and relevant data were assessed and extracted thereafter. Meta-DiSc and STATA softwares were used to pool the accuracy parameters from the extracted data.
RESULTS
A total of 33 eligible studies were identified for this systemic review and meta-analysis. After pooling, the overall sensitivity, specificity, and diagnostic odds ratio were 0.77 (95%CI: 0.74-0.79), 0.87 (95%CI: 0.85-0.89), and 23.96 (95%CI: 13.72-41.84), respectively. The overall positive and negative likelihood ratios were 5.55 (95%CI: 3.76-8.19) and 0.29 (95%CI: 0.21-0.38), respectively. Area under curve of the summarized ROC curve was 0.8992.
CONCLUSION
Digital polymerase chain reaction, amplification refractory mutation system, and next-generation sequencing had overall high accuracy in detecting KRAS mutation in cell-free DNA sample. Large prospective randomized clinical trials are needed to further convince the accuracy and usefulness of KRAS mutation detection using cfDNA/liquid biopsy samples in clinical practice.
TRIAL REGISTRATION
PROSPERO CRD42020176682; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176682.
Topics: Circulating Tumor DNA; Colorectal Neoplasms; High-Throughput Nucleotide Sequencing; Humans; Mutation; Odds Ratio; Polymerase Chain Reaction; Proto-Oncogene Proteins p21(ras); Publication Bias; Publications; ROC Curve
PubMed: 33770081
DOI: 10.1371/journal.pone.0248775 -
Annals of Clinical Microbiology and... Aug 2023The emergence of multidrug-resistant (MDR) strains of genital pathogens, notably Mycoplasma genitalium and Ureaplasma spp., constitutes a significant global threat... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The emergence of multidrug-resistant (MDR) strains of genital pathogens, notably Mycoplasma genitalium and Ureaplasma spp., constitutes a significant global threat today. The present study aimed to evaluate the prevalence and trend of changes in MDR mycoplasma and ureaplasma strains.
METHODS
An exhaustive search was performed across the ISI Web of Science, PubMed, Scopus, ScienceDirect, and Google Scholar databases to accumulate relevant studies without restrictions until April 2023. We used event rate and corresponding 95% confidence intervals to determine the frequency of resistance-related mutations and examine the trend of antibiotic resistance changes.
RESULTS
The data from 27 studies, including 24,662 patients across 14 countries, were evaluated. Out of the total studies, 20 focused on M. genitalium infections, and five on Ureaplasma spp. The frequency of resistance-associated mutations to macrolides, tetracyclines, and fluoroquinolones in clinical strains of M. genitalium was 43.5%, 13.1%, and 18.6%, respectively. The prevalence of M. genitalium strains with double resistance and MDR was 11.0% and 17.4%, respectively. The incidence of both double-drug-resistant and MDR strains was higher in the World Health Organization (WHO) Western Pacific Region than in European and American populations. For Ureaplasma strains, resistance-associated mutations to macrolides, tetracyclines, and fluoroquinolones were 40.8%, 25.7%, and 90.3%, respectively. The rate of antibiotic resistance was higher in the African population compared to the European and WHO Western Pacific Regions. The rate of MDR Ureaplasma infections was 13.2%, with a higher incidence in the African population compared to the WHO Western Pacific and European regions.
CONCLUSION
The proliferation and spread of MDR Mycoplasma and Ureaplasma strains present a significant public health challenge. The situation is indeed alarming, and the rising trend of MDR M. genitalium and MDR Ureaplasma infections suggests that therapies involving macrolides and fluoroquinolones may become less effective.
Topics: Humans; Mycoplasma; Mycoplasma Infections; Ureaplasma Infections; Mycoplasma hominis; Anti-Bacterial Agents; Ureaplasma; Fluoroquinolones; Tetracyclines; Macrolides; Mutation; Prevalence
PubMed: 37563660
DOI: 10.1186/s12941-023-00627-6 -
Scientific Reports Sep 2014Epidermal growth factor receptor (EGFR) mutation is a reliable and sensitive biomarker for EGFR-TKI therapy in non-small-cell lung cancer (NSCLC). However, detection of... (Meta-Analysis)
Meta-Analysis Review
Epidermal growth factor receptor (EGFR) mutation is a reliable and sensitive biomarker for EGFR-TKI therapy in non-small-cell lung cancer (NSCLC). However, detection of EGFR mutation in tissues has obvious limitations. Circulating free DNA (cfDNA) has been reported as an alternative approach for the detection of EGFR mutations. This systematic review and meta-analysis was designed to assess the diagnostic performance of cfDNA, compared with tissues. True-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) values were extracted or calculated for each study. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall diagnostic performance. 20 eligible studies involving 2012 cases were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.674 (95%CI: 0.517-0.800), 0.935 (95%CI: 0.888-0.963), 10.307 (95%CI: 6.167-17.227), 0.348 (95%CI: 0.226-0.537), and 29.582 (95%CI: 4.582-60.012), respectively. The AUC was 0.93 (95% CI: 0.90-0.95). The meta-analysis suggests that detection of EGFR mutation by cfDNA is of adequate diagnostic accuracy and cfDNA analysis could be a promising screening test for NSCLC.
Topics: Antineoplastic Agents; Area Under Curve; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; DNA; ErbB Receptors; Erlotinib Hydrochloride; Female; Gefitinib; Humans; Lung Neoplasms; Male; Mutation; Protein Kinase Inhibitors; Quinazolines; ROC Curve
PubMed: 25201768
DOI: 10.1038/srep06269 -
Hormone Research in Paediatrics 2011The human glucocorticoid receptor (hGR) is a ubiquitously expressed intracellular, ligand-dependent transcription factor, which mediates the action of glucocorticoids... (Review)
Review
CONTEXT
The human glucocorticoid receptor (hGR) is a ubiquitously expressed intracellular, ligand-dependent transcription factor, which mediates the action of glucocorticoids and influences physiological functions essential for life. Alterations in the molecular mechanisms of hGR action impair glucocorticoid signal transduction and alter tissue sensitivity to glucocorticoids. This review summarizes the pathophysiology, molecular mechanisms and clinical aspects of primary generalized glucocorticoid resistance (PGGR) and hypersensitivity (PGGH).
EVIDENCE ACQUISITION
A systematic review of the published, peer-reviewed medical literature (PubMed: 1975 through May 2011) was conducted to identify original articles and reviews on this topic.
EVIDENCE SYNTHESIS
Evidence synthesis was relied upon the experience of a number of experts in the field, including our extensive personal experience.
CONCLUSIONS
The molecular basis of PGGR and PGGH has been ascribed to mutations in the hGR gene, which alter tissue sensitivity to glucocorticoids. The stochastic nature of glucocorticoid signaling pathways in association with the variable effect that hGR gene mutations/polymorphisms might have on glucocorticoid signal transduction indicates that alterations in hGR action may have important implications for many critical biological processes, such as the behavioral and physiological responses to stress, the immune and inflammatory reaction, as well as growth and reproduction.
Topics: Diagnostic Techniques, Endocrine; Drug Hypersensitivity; Drug Resistance; Genetic Diseases, Inborn; Glucocorticoids; Humans; Models, Biological; Mutation; Receptors, Glucocorticoid
PubMed: 21912096
DOI: 10.1159/000330759 -
Oral Oncology May 2023To estimate the prevalence of two most common and mutually exclusive -124 C > T and -146 C > T TERT promoter mutations in HNSCC and analyse their prognostic role. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To estimate the prevalence of two most common and mutually exclusive -124 C > T and -146 C > T TERT promoter mutations in HNSCC and analyse their prognostic role.
MATERIALS AND METHODS
The databases Medline (via Ovid), Embase (via Ovid), Cochrane Library, Scopus, and Web of Science (Core Collection) were searched from inception to December 2022 to identify studies analysing TERT promoter mutations in HNSCC. Pooled prevalence of TERT promoter mutations and hazard ratio (sHR) of death/progression, with corresponding confidence intervals (CI), were estimated.
RESULTS
The initial search returned 6416 articles, of which 17 studies, including 1830 patients, met the criteria for prevalence meta-analysis. Among them, 8 studies fitted the inclusion criterion to analyse the prognostic impact of TERT promoter mutations. Overall, 21% (95% CI: 12%-31%) of HNSCCs harboured TERT promoter mutation. TERT promoter mutations were more commonly found in oral cavity cancer (prevalence = 47%, 95% CI: 33%-61%), followed by laryngeal/hypopharyngeal cancer (prevalence = 12%, 95% CI: 4%-25%), while they were quite rare in oropharyngeal cancer (prevalence = 1%, 95% CI: 0%-4%). TERT promoter mutation -124 C > T was associated with a higher risk of death (sHR = 2.01, 95% CI: 1.25-3.23) and progression (sHR = 2.79, 95% CI: 1.77-4.40), while -146 C > T TERT promoter mutation did not show any significant correlation neither to overall nor progression-free survival.
CONCLUSION
TERT promoter mutations were mainly topographically restricted to oral cavity cancer. -124 C > T was the most common TERT promoter mutation and was significantly associated to worse outcome in HNSCC.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Prognosis; Prevalence; Mouth Neoplasms; Laryngeal Neoplasms; Telomerase; Head and Neck Neoplasms; Mutation
PubMed: 37075587
DOI: 10.1016/j.oraloncology.2023.106398 -
Annals of Internal Medicine Jan 2011KRAS mutations have been extensively investigated as predictive biomarkers for treatment of advanced colorectal cancer with the anti-epidermal growth factor receptor... (Review)
Review
BACKGROUND
KRAS mutations have been extensively investigated as predictive biomarkers for treatment of advanced colorectal cancer with the anti-epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab.
PURPOSE
To summarize whether KRAS mutation status modifies effects of anti-EGFR-based treatments for patients with advanced colorectal cancer and whether KRAS status predicts clinical outcomes among such patients.
DATA SOURCES
MEDLINE and 2 curated genetics databases (through 24 March 2010) were searched for observational studies. MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects (through 1 September 2010) were searched for randomized, controlled trials. No search was restricted by language.
STUDY SELECTION
Three reviewers screened titles and abstracts to identify published studies assessing KRAS mutations as predictors of overall and progression-free survival or treatment failure for patients who received anti-EGFR-based therapy for metastatic colorectal cancer.
DATA EXTRACTION
Three investigators extracted data on population and study-design characteristics, including quality items, and on outcomes of interest. Random-effects meta-analyses were done on nonoverlapping studies.
DATA SYNTHESIS
In 4 reanalyses of randomized trials of anti-EGFR-based therapy versus best supportive care or cytotoxic chemotherapy, no significant benefit was found for overall or progression-free survival from anti-EGFR-based treatment among KRAS-positive patients (hazard ratio [HR], 1.0). However, evidence favors anti-EGFR therapy among KRAS wild-type patients; the relative HR across KRAS-positive and wild-type patients was 1.30 (95% CI, 0.95 to 1.78) for overall survival and 2.22 (CI, 1.74 to 2.84) for progression-free survival by random-effects meta-analysis. In 13 cohorts of patients who received anti-EGFR antibodies, the summary HR for overall survival was 1.79 (CI, 1.48 to 2.17), with better survival in wild-type patients. The corresponding HR for progression-free survival was 2.11 (CI, 1.74 to 2.55 [16 cohorts]). In random-effects bivariate meta-analysis of 22 studies, the summary sensitivity of KRAS mutations for predicting lack of response was 0.49 (CI, 0.43 to 0.55), and summary specificity was 0.93 (CI, 0.87 to 0.97).
LIMITATIONS
Limited evidence from randomized studies exists. Patient-level data are needed to assess modifiers of the mutation-by-treatment interaction. Publication bias could be a concern.
CONCLUSION
KRAS mutations are consistently associated with reduced overall and progression-free survival and increased treatment failure rates among patients with advanced colorectal cancer treated with anti-EGFR antibodies.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Cetuximab; Colorectal Neoplasms; Disease Progression; Disease-Free Survival; ErbB Receptors; Humans; Mutation; Panitumumab; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Treatment Failure; ras Proteins
PubMed: 21200037
DOI: 10.7326/0003-4819-154-1-201101040-00006