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Cancer Cell International 2018Many studies have investigated the prognostic role of biomarkers in colorectal liver metastases (CRLM). However, no biomarker has been established in routine clinical... (Review)
Review
BACKGROUND
Many studies have investigated the prognostic role of biomarkers in colorectal liver metastases (CRLM). However, no biomarker has been established in routine clinical practice. The aim of this study was to scrutinize the current literature for biomarkers evaluated by immunohistochemistry as prognostic markers in patients with resected CRLM.
METHODS
A systematic review was performed according to the PRISMA guidelines. Articles were identified in the PubMed database with selected search terms and by cross-references search. The REMARK quality criteria were applied. Markers were included if they reported the prognostic impact of immunohistochemical markers in a multivariable setting in relation to overall survival (OS). A meta-analysis was conducted when more than one original article provided survival data of a marker.
RESULTS
In total, 26 biomarkers were identified as independent significant markers for OS in resected CRLM. These biomarkers were found to be involved in multiple oncogenic signalling pathways that control cell growth, apoptosis, angiogenesis and evasion of immune detection. Among these biomarker candidates were Ki-67, EGFR, p53, hTERT, CD34, TSP-1, KISS1, Aurora kinase A and CDX2. CD34 and TSP-1 were reported as significantly associated with survival by more than one study and where therefore pooled in a meta-analysis.
CONCLUSION
A number of independent prognostic biomarkers for resected CRLM were identified. However, most markers were evaluated in a retrospective setting with small patient cohorts, without external validation. Large, prospective, multicentre studies with standardised methods are needed before biomarkers can translated into the clinic.
PubMed: 30602942
DOI: 10.1186/s12935-018-0715-8 -
Ultrasound in Obstetrics & Gynecology :... May 2019To assess the added value of chromosomal microarray analysis (CMA) over conventional karyotyping to assess the genetic causes in stillbirth. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the added value of chromosomal microarray analysis (CMA) over conventional karyotyping to assess the genetic causes in stillbirth.
METHODS
To identify relevant studies, published in English or Spanish and without publication time restrictions, we performed a systematic search of PubMed, SCOPUS and ISI Web of Science databases, The Cochrane Library and the PROSPERO register of systematic reviews, for case series of fetal loss ≥ 20 weeks of gestation, with normal or suspected normal karyotype, undergoing CMA and with at least five subjects analyzed. To investigate quality, two reviewers evaluated independently the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. For the meta-analysis, the incremental yield of CMA over karyotyping was assessed by single-proportion analysis using a random-effects model (weighting by inverse variance). We assessed heterogeneity between studies and performed a sensitivity analysis and a subgroup analysis of structurally abnormal (malformed or growth-restricted) and normal fetuses.
RESULTS
Included in the meta-analysis were seven studies involving 903 stillborn fetuses which had normal karyotype. The test success rate achieved by conventional cytogenetic analysis was 75%, while that for CMA was 90%. The incremental yield of CMA over conventional karyotyping based on the random-effects model was 4% (95% CI, 3-5%) for pathogenic copy-number variants (pCNVs) and 8% (95% CI, 4-17%) for variants of unknown significance. Subgroup analysis showed a 6% (95% CI, 4-10%) incremental yield of CMA for pCNVs in structurally abnormal fetuses and 3% (95% CI, 1-5%) incremental yield for those in structurally normal fetuses. The pCNV found most commonly was del22q11.21.
CONCLUSIONS
CMA, incorporated into the stillbirth work-up, improves both the test success rate and the detection of genetic anomalies compared with conventional karyotyping. To achieve a genetic diagnosis in stillbirth is particularly relevant for the purpose of counseling regarding future pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Chromosome Aberrations; Female; Fetal Diseases; Humans; Karyotyping; Microarray Analysis; Pregnancy; Stillbirth
PubMed: 30549343
DOI: 10.1002/uog.20198 -
Journal of Korean Medical Science Mar 2024Ultrasonographic soft markers are normal variants, rather than fetal abnormalities, and guidelines recommend a detailed survey of fetal anatomy to determine the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ultrasonographic soft markers are normal variants, rather than fetal abnormalities, and guidelines recommend a detailed survey of fetal anatomy to determine the necessity of antenatal karyotyping. Anecdotal reports have described cases with ultrasonographic soft markers in which chromosomal microarray analysis (CMA) revealed pathogenic copy number variants (CNVs) despite normal results on conventional karyotyping, but CMA for ultrasonographic soft markers remains a matter of debate. In this systematic review, we evaluated the clinical significance of CMA for pregnancies with isolated ultrasonographic soft markers and a normal fetal karyotype.
METHODS
An electronic search was conducted by an experienced librarian through the MEDLINE, Embase, and Cochrane CENTRAL databases. We reviewed 3,338 articles (3,325 identified by database searching and 13 by a hand search) about isolated ultrasonographic soft markers, and seven ultrasonographic markers (choroid plexus cysts, echogenic bowel, echogenic intracardiac focus, hypoplastic nasal bone, short femur [SF], single umbilical artery, and urinary tract dilatation) were included for this study.
RESULTS
Seven eligible articles were included in the final review. Pathogenic or likely pathogenic CNVs were found in fetuses with isolated ultrasonographic soft markers and a normal karyotype. The overall prevalence of pathogenic or likely pathogenic CNVs was 2.0% (41 of 2,048). The diagnostic yield of CMA was highest in fetuses with isolated SF (9 of 225, 3.9%).
CONCLUSION
CMA could aid in risk assessment and pregnancy counseling in pregnancies where the fetus has isolated ultrasonographic soft markers along with a normal karyotype.
Topics: Female; Humans; Pregnancy; Fetus; Karyotyping; Microarray Analysis; Ultrasonography, Prenatal
PubMed: 38442716
DOI: 10.3346/jkms.2024.39.e70 -
Prenatal Diagnosis Apr 2024Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities.
METHODS
Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model.
RESULTS
Thirty studies were included (n = 1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%-36%; I = 72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%-34%; I = 74%]; (b) single CNS anomaly; 16% [95% CI 10%-23%; I = 41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%-40%; I = 56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%-57%; I = 68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus.
CONCLUSIONS
Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.
Topics: Pregnancy; Female; Humans; Prospective Studies; Hydrocephalus; Nervous System Malformations; Karyotyping; Karyotype; Fetus; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 38054560
DOI: 10.1002/pd.6466 -
Medicine Feb 2022Diabetic nephropathy (DN) is a common microvascular complication of diabetic patients, along with hypertension, hyperlipemia, proteinuria, edema, and other clinical...
Diabetic nephropathy (DN) is a common microvascular complication of diabetic patients, along with hypertension, hyperlipemia, proteinuria, edema, and other clinical manifestations. Astragalus membranaceus (AM) is a traditional Chinese medicine and has shown significant clinical efficacy against DN. However, the overall molecular mechanism of this therapeutic effect has not been entirely elucidated. Using network pharmacology, we aimed to identify the key active ingredients and potential pharmacological mechanisms of AM in treating DN and provide scientific evidence of its clinical efficacy.The active ingredients of AM were obtained from the traditional Chinese medicine systems pharmacology database, and the potential targets of AM were identified using the therapeutic target database. DN-related target genes were acquired from the Gene Expression Omnibus microarray dataset GSE1009 and 3 widely used databases-DisGeNET, GeneCards, and Comparative Toxicogenomics Database. The DN-AM common target protein interaction network was established by using the STRING database. Active ingredients candidate targets proteins networks were constructed using Cytoscape software for visualization. Additionally, gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathway analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery database. Target-regulating microRNAs (miRNAs) of these hub genes were obtained from the therapeutic target database, which could then be used for further identification of AM-regulated key miRNAs.A total of 17 active ingredients and 214 target proteins were screened from AM. 61 candidate co-expressed genes with therapeutic effects against DN were obtained and considered as potential therapeutic targets. GO and Kyoto encyclopedia of genes and genomes enrichment analysis showed that these genes were mainly involved in inflammatory response, angiogenesis, oxidative stress reaction, HIF signaling pathway, tumor necrosis factor signaling pathway, and VEGF signaling pathway. In all, 636 differentially expressed genes were identified between the DN patients and control group by using microarray data, GSE1009. Lastly, VEGFA, epidermal growth factor receptor, STAT1, and GJA1 were screened as hub genes. The relationships between miRNAs and hub genes were constructed, which showed that miR-302-3p, miR-372-3p, miR-373-3p, and miR-520-3p were regulated by VEGFA and epidermal growth factor receptor. Meanwhile, VEGFA also influenced miR-15-5p, miR-16-5p, miR-17-5p, miR-20-5p, miR-93-5p, miR-106-5p, miR-195-5p, miR-424-5p, miR-497-5p, and miR-519-3p. In addition, miR-1-3p and miR-206 were regulated by VEGFA and GJA1, and miR-23-3p was regulated by STAT1 and GJA1.To our knowledge, this study revealed for the first time the characteristic multiple components, multiple targets, and multiple pathways of AM that seem to be the underlying mechanisms of action of AM in the treatment of DN with respect to miRNAs.Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.
Topics: Astragalus propinquus; Diabetes Mellitus; Diabetic Nephropathies; Drugs, Chinese Herbal; ErbB Receptors; Humans; Medicine, Chinese Traditional; MicroRNAs; Network Pharmacology
PubMed: 35119030
DOI: 10.1097/MD.0000000000028747 -
Medicine Dec 2016As environmental risk factors (ERFs) play an important role in the pathogenesis of Kashin-Beck disease (KBD), it is important to identify the interaction between ERFs... (Meta-Analysis)
Meta-Analysis Review
As environmental risk factors (ERFs) play an important role in the pathogenesis of Kashin-Beck disease (KBD), it is important to identify the interaction between ERFs and differentially expression genes (DEGs) in KBD. The environmental response genes (ERGs) were analyzed in cartilage of KBD in comparison to normal controls.We searched 5 English and 3 Chinese databases from inception to September 2015, to identify case-control studies that examined ERFs for KBD using integrative meta-analysis and systematic review. Total RNA was isolated from articular cartilage of KBD patients and healthy controls. Human whole genome microarray chip (Agilent) was used to analyze the amplified, labeled, and hybridized total RNA, and the validated microarray data were partially verified using real-time quantitative polymerase chain reaction (qRT-PCR). The ERGs were derived from the Comparative Toxicogenomics Database. The identified ERGs were subjected to KEGG pathway enrichment, biological process (BP), and interaction network analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.7, and STRING.The trace elements (selenium and iodine), vitamin E, and polluted grains (T-2 toxin/HT-2 toxin, deoxynivalenol, and nivalenol) were identified as the ERFs for KBD using meta-analysis and review. We identified 21 upregulated ERGs and 7 downregulated ERGs in cartilage with KBD compared with healthy controls, which involved in apoptosis, metabolism, and growth and development. KEGG pathway enrichment analysis found that 2 significant pathways were involved with PI3K-Akt signaling pathway and P53 signaling pathway, and gene ontology function analysis found 3 BPs involved with apoptosis, death, and cell death in KBD cartilage.According to previous results and our own research, we suggest that the trace element selenium and vitamin E induce PI3K-Akt signaling pathway and the mycotoxins (T-2 toxin/HT-2 toxin and DON) induce P53 signaling pathway, contributing to the development of KBD, and chondrocyte apoptosis and cell death.
Topics: Apoptosis; Cartilage, Articular; Case-Control Studies; Down-Regulation; Gene Expression; Gene Expression Profiling; Gene Ontology; Gene-Environment Interaction; Humans; Kashin-Beck Disease; Oncogene Protein v-akt; Phosphatidylinositol 3-Kinases; Risk Factors; Signal Transduction; Tumor Suppressor Protein p53; Up-Regulation
PubMed: 28033256
DOI: 10.1097/MD.0000000000005669 -
Frontiers in Plant Science 2021Herbivore oviposition produces all sorts of responses in plants, involving wide and complex genetic rearrangements. Many transcriptomic studies have been performed to...
Herbivore oviposition produces all sorts of responses in plants, involving wide and complex genetic rearrangements. Many transcriptomic studies have been performed to understand this interaction, producing a bulk of transcriptomic data. However, the use of many transcriptomic techniques across the years, the lack of comparable transcriptomic context at the time of publication, and the use of outdated databases are limitations to understand this biological process. The current analysis intends to retrieve oviposition studies and process them with up-to-date techniques and updated databases. To reduce heterogeneities, the same processing techniques were applied, and Arabidopsis was selected to avoid divergencies on plant taxa stress response strategies. By doing so, we intended to understand the major mechanisms and regulatory processes linked to oviposition response. Differentially expressed gene (DEG) identification and co-expression network-based analyses were the main tools to achieve this goal. Two microarray studies and three RNA-seq analyses passed the screening criteria. The collected data pertained to the lepidopteran and the mite , and covered a timeline from 3 to 144 h. Among the 18, 221 DEGs found, 15, 406 were exclusive of (72 h) and 801 were exclusive for the rest of the experiments. Excluding (72 h), shared genes on the rest of the experiments were twice the unique genes, indicating common response mechanisms were predominant. Enrichment analyses indicated that shared processes were circumscribed to earlier time points, and after 24 h, the divergences escalated. The response was characterized by patterns of time-dependent waves of unique processes. oviposition induced a rich response that shared functions across time points, while eggs triggered less but more diverse time-dependent functions. The main processes altered were associated with hormonal cascades [e.g., salicilic acid (SA) and jasmonic acid (JA)], defense [reactive oxygen species (ROS) and glucosinolates], cell wall rearrangements, abiotic stress responses, and energy metabolism. Key gene drivers of the identified processes were also identified and presented. The current results enrich and clarify the information regarding the molecular behavior of the plant in response to oviposition by herbivores. This information is valuable for multiple stress response engineering tools, among other applications.
PubMed: 35126411
DOI: 10.3389/fpls.2021.772492 -
Aging Dec 2020Dysregulation of α(1,6)-fucosyltransferase (FUT8) plays significant roles in development of a variety of malignant tumor types. We collected as many relevant articles... (Meta-Analysis)
Meta-Analysis
Dysregulation of α(1,6)-fucosyltransferase (FUT8) plays significant roles in development of a variety of malignant tumor types. We collected as many relevant articles and microarray datasets as possible to assess the prognostic value of FUT8 expression in malignant tumors. For this purpose, we systematically searched PubMed, Embase, Web of Science, Springer, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang, and eventually identified 7 articles and 35 microarray datasets (involving 6124 patients and 10 tumor types) for inclusion in meta-analysis. In each tumor type, FUT8 expression showed significant (p< 0.05) correlation with one or more clinicopathological parameters; these included patient gender, molecular subgroup, histological grade, TNM stage, estrogen receptor, progesterone receptor, and recurrence status. In regard to survival prognosis, FUT8 expression level was associated with overall survival in non-small cell lung cancer (NSCLC), breast cancer, diffuse large B cell lymphoma, gastric cancer, and glioma. FUT8 expression was also correlated with disease-free survival in NSCLC, breast cancer, and colorectal cancer, and with relapse-free survival in pancreatic ductal adenocarcinoma. For most tumor types, survival prognosis of patients with high FUT8 expression was related primarily to clinical features such as gender, tumor stage, age, and pathological category. Our systematic review and meta-analysis confirmed the association of FUT8 with clinicopathological features and patient survival rates for numerous malignant tumor types. Verification of prognostic value of FUT8 in these tumor types will require a large-scale study using standardized methods of detection and analysis.
Topics: Biomarkers, Tumor; Fucosyltransferases; Gene Expression Regulation, Neoplastic; Humans; Neoplasms
PubMed: 33323540
DOI: 10.18632/aging.202239 -
Journal of Assisted Reproduction and... Jul 2016The purpose of the review was to define the various diagnostic platforms currently available to perform preimplantation genetic testing for aneuploidy and describe in a... (Review)
Review
PURPOSE
The purpose of the review was to define the various diagnostic platforms currently available to perform preimplantation genetic testing for aneuploidy and describe in a clear and balanced manner the various strengths and weaknesses of these technologies.
METHODS
A systematic literature review was conducted. We used the terms "preimplantation genetic testing," "preimplantation genetic diagnosis," "preimplantation genetic screening," "preimplantation genetic diagnosis for aneuploidy," "PGD," "PGS," and "PGD-A" to search through PubMed, ScienceDirect, and Google Scholar from the year 2000 to April 2016. Bibliographies of articles were also searched for relevant studies. When possible, larger randomized controlled trials were used. However, for some emerging data, only data from meeting abstracts were available.
RESULTS
PGS is emerging as one of the most valuable tools to enhance pregnancy success with assisted reproductive technologies. While all of the current diagnostic platforms currently available have various advantages and disadvantages, some platforms, such as next-generation sequencing (NGS), are capable of evaluating far more data points than has been previously possible. The emerging complexity of different technologies, especially with the utilization of more sophisticated tools such as NGS, requires an understanding by clinicians in order to request the best test for their patients..
CONCLUSION
Ultimately, the choice of which diagnostic platform is utilized should be individualized to the needs of both the clinic and the patient. Such a decision must incorporate the risk tolerance of both the patient and provider, fiscal considerations, and other factors such as the ability to counsel patients on their testing results and how these may or may not impact clinical outcomes.
Topics: Aneuploidy; Blastocyst; Female; Fertilization in Vitro; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Pregnancy; Preimplantation Diagnosis; Real-Time Polymerase Chain Reaction
PubMed: 27299602
DOI: 10.1007/s10815-016-0740-2 -
Dose-response : a Publication of... 2019Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and... (Review)
Review
Analysis of mRNA Expression Patterns in Peripheral Blood Cells of 3 Patients With Cancer After the First Fraction of 2 Gy Irradiation: An Integrated Case Report and Systematic Review.
BACKGROUND
Radiation therapy induces acute and chronic radiological toxicity, in particular hematological toxicity (HT). This study aimed to explore the mechanistic clue and potential predictors at the messenger RNA (mRNA) level.
MATERIALS AND METHODS
Peripheral blood was collected from 3 patients with cervical cancer (CC), nasopharynx cancer (NC), and tongue cancer (TC) after the first 2 Gy fraction of radiotherapy (RT). High-throughput sequencing was used to assess mRNA profiles.
RESULTS
Eleven genes, such as ALAS2(5-aminolevulinate synthase), SLC4A1(solute carrier family 4 member 1), (hemoglobin subunit gamma 2), (TNF α-induced protein 3), (period circadian clock 1), (coiled-coil domain containing 136), (chromosome 9 open reading frame 84), (interleukin 1β), (FosB protooncogene), (nuclear receptor subfamily 4), (polymerase family member 15), had overlapping expression changes in all 3 cancers of which 3 (, and ) are suggested as potential predictors for the early diagnosis of HT after RT.
CONCLUSIONS
may be useful predictors of HT in patients after RT. Eleven overlapping expression mRNAs among 3 cancers might be potential predictors for early diagnosis of radiation toxicity in patients.
PubMed: 30833875
DOI: 10.1177/1559325819833474