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European Journal of Human Genetics :... Sep 2013Prostate cancer (PCa) is a worldwide disease that affects a large number of males. Although prostate-specific antigen (PSA) screening is used, the specificity is... (Meta-Analysis)
Meta-Analysis Review
Prostate cancer (PCa) is a worldwide disease that affects a large number of males. Although prostate-specific antigen (PSA) screening is used, the specificity is limited. This study analyzes the sensitivity and specificity of adenomatous polyposis coli (APC) methylation for PCa detection in body fluids and tissues. Combining search results from PubMed and Embase, 19 studies were included, 5 involving body fluids and 14 involving prostate tissue, with 2344 subjects. In body fluid subgroups, the pooled sensitivity and specificity was 0.53 (95% confidence interval (CI): 0.28-0.78) and 0.92 (95% CI: 0.86-0.95), respectively. From tissue studies, the results presented as 0.84 (95% CI: 0.70-0.92) and 0.91 (95% CI: 0.77-0.97). To confirm the results, we conducted a further analysis by removing studies which introduced high heterogeneity due to the type of cases and controls. The same degree of sensitivity and specificity was presented in two subgroups (urine: sensitivity 0.46, 95% CI: 0.39-0.53; specificity 0.87, 95% CI: 0.64-0.96; tissue: sensitivity 0.87, 95% CI: 0.72-0.94; specificity 0.89, 95% CI: 0.68-0.97). In addition, analysis of the interaction between APC methylation and PCa showed strong association in the whole data set (odds ratio (OR)=24.91, 95% CI: 12.86-48.24, I(2)=72.5%). Pooling the same two main subgroups (tissue/fluid) gave a pooled OR of 33.54 (95% CI: 14.88-75.59; I(2)=70.7%) and 8.20 (95% CI: 2.84-23.74, I(2)=64.2%), respectively. From this study, the results suggest that APC promoter methylation may be the potential testing for PCa diagnosis and provide a new viewpoint in the treatment of PCa.
Topics: Adenomatous Polyposis Coli Protein; Case-Control Studies; DNA Methylation; Genetic Association Studies; Humans; Male; Promoter Regions, Genetic; Prostatic Neoplasms; Sensitivity and Specificity
PubMed: 23299921
DOI: 10.1038/ejhg.2012.281 -
Middle East Journal of Digestive... Jul 2022: With a global prevalence of about 10%, gastric cancer is among the most prevalent cancers. Currently, there has been an ongoing trend toward investigating genetic... (Review)
Review
: With a global prevalence of about 10%, gastric cancer is among the most prevalent cancers. Currently, there has been an ongoing trend toward investigating genetic disruptions in different cancers because they can be used as a target-specific therapy. We aimed to systemically review some gene expression patterns in gastric cancer. : The current systematic review was designed and executed in 2020. Scopus, PubMed, Cochrane Library, Google Scholar, web of knowledge, and Science Direct were searched for relevant studies. A manual search of articles (hand searching), reference exploring, checking for grey literature, and seeking expert opinion were also done. : In this review, 65 studies were included, and the expression pattern of HER2/ ERBB2, ER1/Erb1/EGFR, PIK3CA, APC, KRAS, ARID1A, TP53, FGFR2 and MET was investigated. TP53, APC, KRAS, and PIK3CA mutation cumulative frequency were 24.8 (I=95.05, Q value=525.53, df=26, <0.001), 7.2 (I=89.79, Q value=48.99, df=5, <0.001), 7.8 (I=93.60, Q value=140.71, df=9, =0.001) and 8.6 (I=80.78, Q value=525.53, df=9, <0.001) percent, respectively. Overexpression was investigated for HER1/ Erb1/EGFR, PIK3CA, APC, KRAS, ARID1A, TP53, CCND1, FGFR2, MET and MYC. The frequency of TP53 and HER2/ERBB2 were 43.1 (I=84.06, Q value=58.09, df=9, <0.001) and 20.8 (I=93.61, Q value=234.89, df=15, <0.001) percent, respectively. : More research is encouraged to investigate the genes for which we could not perform a meta-analysis.
PubMed: 36619267
DOI: 10.34172/mejdd.2022.292 -
Laryngoscope Investigative... Aug 2021Olfactory neuroblastoma (ONB) or esthesioneuroblastoma (ENB) is a rare malignancy of the nasal cavity believed to arise from the olfactory epithelium. The goal of this... (Review)
Review
BACKGROUND
Olfactory neuroblastoma (ONB) or esthesioneuroblastoma (ENB) is a rare malignancy of the nasal cavity believed to arise from the olfactory epithelium. The goal of this study was to systematically review the genomics, epigenetics, and cytogenetics of ONB and to understand the potential clinical implications of these studies.
METHODS
A systematic literature review was performed for articles published before May 2020 using Cochrane, Embase, Pubmed, and Scopus databases. Inclusion criteria included genomics, cytogenetics, and epigenetics studies on ONB. Exclusion criteria included studies not in English or systematic reviews. Articles and abstracts were reviewed by two independent reviewers to reduce bias during article selection and synthesis of results. Of the 36 studies included in this review, 24 were research articles and 12 were abstracts.
RESULTS
Although recurrent mutations among ONB tumors are uncommon, alterations in , , , , , , , , , , , , , , , and genes have been reported in several recent studies. In addition, cytogenetic studies revealed that the landscape of chromosomal aberrations varies widely amongst ONB tumors.
CONCLUSIONS
The rare character of ONB has limited the sample size available for cytogenetic, genomic, and epigenetic studies and contributes to the limitations of this systematic review. Comprehensive genomic and epigenomic studies with larger cohorts are warranted to validate the initial reports summarized in this review and to identify potential therapeutic targets for ONB.
PubMed: 34401496
DOI: 10.1002/lio2.597 -
HGG Advances Jan 2023To identify Lynch syndrome (LS) carriers, DNA mismatch repair (MMR) immunohistochemistry (IHC) is performed on colorectal cancers (CRCs). Upon subsequent LS diagnostics,...
To identify Lynch syndrome (LS) carriers, DNA mismatch repair (MMR) immunohistochemistry (IHC) is performed on colorectal cancers (CRCs). Upon subsequent LS diagnostics, MMR deficiency (MMRd) sometimes remains unexplained (UMMRd). Recently, the importance of complete LS diagnostics to explain UMMRd, involving MMR methylation, germline, and somatic analyses, was stressed. To explore why some MMRd CRCs remain unsolved, we performed a systematic review of the literature and mapped patients with UMMRd diagnosed in our center. A systematic literature search was performed in Ovid Medline, Embase, Web of Science, Cochrane CENTRAL, and Google Scholar for articles on UMMRd CRCs after complete LS diagnostics published until December 15, 2021. Additionally, UMMRd CRCs diagnosed in our center since 1993 were mapped. Of 754 identified articles, 17 were included, covering 74 patients with UMMRd. Five CRCs were microsatellite stable. Upon complete diagnostics, 39 patients had single somatic MMR hits, and six an MMR germline variant of unknown significance (VUS). Ten had somatic pathogenic variants (PVs) in , , , and . The remaining 14 patients were the only identifiable cases in the literature without a plausible identified cause of the UMMRd. Of those, nine were suspected to have LS. In our center, complete LS diagnostics in approximately 5,000 CRCs left seven MMRd CRCs unexplained. All had a somatic MMR hit or MMR germline VUS, indicative of a missed second MMR hit. In vitually all patients with UMMRd, complete LS diagnostics suggest MMR gene involvement. Optimizing detection of currently undetectable PVs and VUS interpretation might explain all UMMRd CRCs, considering UMMRd a case closed.
Topics: Humans; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; Colorectal Neoplasms, Hereditary Nonpolyposis; Brain Neoplasms
PubMed: 36624813
DOI: 10.1016/j.xhgg.2022.100167 -
Medicine Apr 2020The methylation status of the adenomatous polyposis coli (APC) promoter has been shown to be associated with the occurrence of gastric cancer, but this finding remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The methylation status of the adenomatous polyposis coli (APC) promoter has been shown to be associated with the occurrence of gastric cancer, but this finding remains controversial. The aim of this study was to investigate the relationship between methylation of the APC gene promoter and gastric cancer.
METHODS
We searched the Web of Science, EMBASE, Medline, and Cochrane Central Register of Controlled Trials (CENTRAL) databases from the date of creation until August 1, 2019. According to the inclusion criteria, the relationship between the methylation status of the APC gene promoter and gastric cancer was investigated. The incidence of APC promoter methylation in the tissues or blood of patients with and without gastric cancer was compared. The results are expressed as the odds ratio (OR) and 95% confidence interval (CI). The pooled OR of each study was estimated using a fixed effects model or a random effects model to generate forest plots. We further validated the results using the MethHC database.
RESULTS
Eight studies (985 samples) were included. Our meta-analysis showed that the incidence of APC promoter methylation in patients with gastric cancer was higher than that of patients without gastric cancer (OR = 3.86, 95% CI 1.71-8.74, P = .001). Methylation of the APC promoter is associated with the incidence of gastric cancer, and it increases the risk of gastric cancer.
CONCLUSION
This study provides a new strategic direction for research on gastric cancer. Methylation of the APC promoter may be a potential biomarker for the diagnosis of gastric cancer, but the results of this work require further confirmation.
Topics: Adenomatous Polyposis Coli; Biomarkers, Tumor; Computational Biology; DNA Methylation; Genes, APC; Genetic Predisposition to Disease; Humans; Incidence; Promoter Regions, Genetic; Risk Factors; Stomach Neoplasms
PubMed: 32312003
DOI: 10.1097/MD.0000000000019828 -
Genetics Research 2022Accumulating evidence indicates that the expression and/or variants of several genes play an essential role in the progress of colorectal cancer (CRC). The current study... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Accumulating evidence indicates that the expression and/or variants of several genes play an essential role in the progress of colorectal cancer (CRC). The current study is a meta-analysis undertaken to estimate the prognosis and survival associated with , , , , , and genes among CRC patients.
METHODS
The authors searched PubMed, EMBASE, and Science Direct for relevant reports published between 2000 and 2020 and analyzed them to determine any relationship between the (immunohistochemically/sequencing-detected) gene expression and variants of the selected genes and the survival of CRC patients.
RESULTS
The analysis included 34,074 patients from 64 studies. To evaluate association, hazard ratios (HRs) were estimated for overall survival (OS) or disease-free survival (DFS), with a 95% confidence interval (CIs). Pooled results showed that overexpression, mutation, or 4 loss of expression, mutations, and expression were associated with shorter OS. overexpression (HR: 0.137 (95% CI: 0.131-0.406)), loss of expression of or 4 (HR: 0.449 (95% CI: 0.146-0.753)), the mutations of (HR: 0.179 (95% CI: 0.126-0.485)), and expression (HR: 0.485 (95% CI: 0.772-0.198)) also presented risk for shorter DFS.
CONCLUSIONS
The present meta-analysis indicates that overexpression or underexpression and variants of , , 4, , and genes potentially acted as unfavorable biomarkers for the prognosis of CRC. The gene was not associated with prognosis.
Topics: Colorectal Neoplasms; Cyclin D1; Genes, bcl-1; Humans; Prognosis; Smad3 Protein; Tumor Suppressor Protein p53; beta Catenin
PubMed: 36072013
DOI: 10.1155/2022/5338956 -
Cancers Aug 2023Lung cancer is the leading cause of cancer-related deaths, and early detection is crucial for improving patient outcomes. Current screening methods using computed... (Review)
Review
Lung cancer is the leading cause of cancer-related deaths, and early detection is crucial for improving patient outcomes. Current screening methods using computed tomography have limitations, prompting interest in non-invasive diagnostic tools such as methylated circulating tumor DNA (ctDNA). The PRISMA guidelines for systematic reviews were followed. The electronic databases MEDLINE, Embase, Web of Science, and Cochrane Library were systematically searched for articles. The search string contained three main topics: Lung cancer, blood, and methylated ctDNA. The extraction of data and quality assessment were carried out independently by the reviewers. In total, 33 studies were eligible for inclusion in this systematic review and meta-analysis. The most frequently studied genes were SHOX2, RASSF1A, and APC. The sensitivity and specificity of methylated ctDNA varied across studies, with a summary sensitivity estimate of 46.9% and a summary specificity estimate of 92.9%. The area under the hierarchical summary receiver operating characteristics curve was 0.81. The included studies were generally of acceptable quality, although they lacked information in certain areas. The risk of publication bias was not significant. Based on the findings, methylated ctDNA in blood shows potential as a rule-in tool for lung cancer diagnosis but requires further research, possibly in combination with other biomarkers.
PubMed: 37568774
DOI: 10.3390/cancers15153959 -
Schizophrenia Bulletin Sep 2023Intestinal microbiota is intrinsically linked to human health. Evidence suggests that the composition and function of the microbiome differs in those with schizophrenia... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND HYPOTHESIS
Intestinal microbiota is intrinsically linked to human health. Evidence suggests that the composition and function of the microbiome differs in those with schizophrenia compared with controls. It is not clear how these alterations functionally impact people with schizophrenia. We performed a systematic review and meta-analysis to combine and evaluate data on compositional and functional alterations in microbiota in patients with psychosis or schizophrenia.
STUDY DESIGN
Original studies involving humans and animals were included. The electronic databases PsycINFO, EMBASE, Web of Science, PubMed/MEDLINE, and Cochrane were systematically searched and quantitative analysis performed.
STUDY RESULTS
Sixteen original studies met inclusion criteria (1376 participants: 748 cases and 628 controls). Ten were included in the meta-analysis. Although observed species and Chao 1 show a decrease in diversity in people with schizophrenia compared with controls (SMD = -0.14 and -0.66 respectively), that did not reach statistical significance. We did not find evidence for variations in richness or evenness of microbiota between patients and controls overall. Differences in beta diversity and consistent patterns in microbial taxa were noted across studies. We found increases in Bifidobacterium, Lactobacillus, and Megasphaera in schizophrenia groups. Variations in brain structure, metabolic pathways, and symptom severity may be associated with compositional alterations in the microbiome. The heterogeneous design of studies complicates a similar evaluation of functional readouts.
CONCLUSIONS
The microbiome may play a role in the etiology and symptomatology of schizophrenia. Understanding how the implications of alterations in microbial genes for symptomatic expression and clinical outcomes may contribute to the development of microbiome targeted interventions for psychosis.
Topics: Humans; Schizophrenia; Gastrointestinal Microbiome; Psychotic Disorders
PubMed: 37210594
DOI: 10.1093/schbul/sbad049 -
Advances in Clinical and Experimental... 2015Colorectal cancer (CRC) has become the third most common cancer in developed countries. Each year more and more people die from CRC. CRC is also one of the most... (Review)
Review
Colorectal cancer (CRC) has become the third most common cancer in developed countries. Each year more and more people die from CRC. CRC is also one of the most effectively studied topics in recent years. It has been found that the key phenomena in CRC development are genetic and inflammatory processes. Well-known genetic bases for the carcinogenesis of CRC include chromosomal changes characteristic of the chromosomal instability pathway which correlates with specific and well-defined genetic alterations (such as APC, K-RAS, DCC and p53) and genomic instability characteristics for the mutator pathway focused on KRAS and BRAF mutations. Recent studies have highlighted the impact of inflammation in CRC, especially elevated levels of pro-inflammatory cytokines. Among important risk factors of colon carcinogenesis are colorectal polyps, which are currently the subject of intense research. Recent studies have shown that different adenomas are characterized by different pathways of carcinogenesis as well as diverse COX-2 expression in various polyps. Understanding the mechanism of inflammatory processes in CRC parallel to basic genetic alterations might allow for effective and targeted treatment.
Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Biomarkers, Tumor; Cell Transformation, Neoplastic; Colon; Colorectal Neoplasms; Cyclooxygenase 2; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; Inflammation; Inflammation Mediators; Mutation; Phenotype; Prognosis; Risk Factors
PubMed: 26469098
DOI: 10.17219/acem/31239 -
Clinical Gastroenterology and... Aug 2020Somatic mosaicism, in which variants arise post-zygotically and are therefore not present in all cells in the body, may be an underestimated cause of colorectal cancer... (Review)
Review
BACKGROUND & AIMS
Somatic mosaicism, in which variants arise post-zygotically and are therefore not present in all cells in the body, may be an underestimated cause of colorectal cancer (CRC) and polyposis syndromes. We performed a systematic review to provide a comprehensive overview of somatic mosaicism in patients with CRC and polyposis syndromes.
METHODS
We searched PubMed through March 2018 to identify reports of mosaicism in patients with CRC or polyposis syndromes. We divided the final set of studies into 3 subgroups describing APC mosaicism, mosaicism in other CRC susceptibility genes, and epigenetic mosaicism.
RESULTS
Of the 232 articles identified in our systematic search, 46 met the criteria for further analysis. Of these, 35 studies described mosaic variants or epimutations in patients with CRC or polyposis syndromes. Nineteen studies described APC mosaicism, comprising a total of 57 patients. Six described mosaicism in genes associated with familial CRC syndromes, such as Lynch and Cowden syndromes. Ten studies described epigenetic mosaicism, sometimes resulting from a germline variant (such as deletion of EPCAM).
CONCLUSIONS
We found that somatic mosaicism is underdiagnosed but critical for determining the clinical management of patients with de novo polyposis who possibly carry mosaic APC variants, and present a decision tree for the clinical management of these patients. Mosaicism in genes associated with susceptibility to CRC contributes to development of other familial CRC syndromes. Heritable epigenetic mosaicism is likely underestimated and could have a dominant pattern of inheritance. However, the inheritance of primary mosaic epimutations, without an underlying genetic cause, is complex and not fully understood.
Topics: Adenomatous Polyposis Coli; Colorectal Neoplasms; Genetic Predisposition to Disease; Humans; Mosaicism; Neoplastic Syndromes, Hereditary
PubMed: 32147591
DOI: 10.1016/j.cgh.2020.02.049