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BMC Medical Genetics Oct 2018Currently, several studies have demonstrated that PRKAA1 polymorphisms conduce to the development of cancer. PRKAA1 gene encodes the AMP-activated protein kinase... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, several studies have demonstrated that PRKAA1 polymorphisms conduce to the development of cancer. PRKAA1 gene encodes the AMP-activated protein kinase summit-α1, and plays an important role in cell metabolism. Thus, we performed a systematic review and meta-analysis of all enrolled eligible case-control studies to obtain a precise correlation between PRKAA1 polymorphism and cancer susceptibility.
METHODS
Extensive retrieve was performed in Web of Science, Google Scholar, PubMed, EMbase, CNKI and Wanfang databases up to August 26, 2018. Odds ratios (ORs) and 95% CIs were performed to evaluate the overall strength of the associations in five models, as well as in subgroup analyses, stratified by ethnicity, cancer type or source of control. Q-test, Egger's test and Begg's funnel plot were applied to evaluate the heterogeneity and publication bias. In-silico analysis was performed to demonstrate the relationship of PRKAA1 expression correlated with cancer tissues and survival time.
RESULTS
Twenty-two case-control studies from 14 publications were enrolled, with 17,068 cases and 20,871 controls for rs13361707, and 2514 cases and 3193 controls for rs10074991. Overall, we identified that the PRKAA1 rs13361707 polymorphism is not significantly associated with cancer susceptibility under all five genetic models. For rs10074991, we revealed a significant decrease risk in allelic comparison model (B vs. A: OR = 0.774, 95% CI = 0.642-0.931, P = 3.376*10), heterozygote comparison model (BA vs. AA: OR = 0.779 95%CI = 0.691-0.877, P = 9.86*10;), and dominant genetic model (BB + BA vs. AA: OR = 0.697 95%CI = 0.533-0.912, P = 4.211*10;). Evidence from TCGA database and GTEx projects indicated that the expression of PRKAA1 in gastric cancer tissue is higher, compared to normal stomach tissue, as well as it in breast cancer and esophageal squamous cell carcinoma. However, the Kaplan-Meier estimate showed that there is no significant difference of OS and RFS between the low and high PRKAA1 TPM groups in gastric cancer, breast cancer, and esophageal carcinoma.
CONCLUSIONS
To sum up, PRKAA1 rs13361707 polymorphism is not participant with the increased risk of cancer, while the A allele of PRKAA1 rs10074991 revealed a significant decrease risk.
Topics: AMP-Activated Protein Kinases; Alleles; Breast Neoplasms; Case-Control Studies; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Gene Expression; Humans; Male; Models, Genetic; Odds Ratio; Polymorphism, Single Nucleotide; Risk; Stomach Neoplasms; Survival Analysis
PubMed: 30340465
DOI: 10.1186/s12881-018-0704-8 -
PloS One 2018Biomarkers commonly assessed in prenatal screening have been associated with a number of adverse perinatal and birth outcomes. However, it is not clear whether first... (Meta-Analysis)
Meta-Analysis
Biomarkers commonly assessed in prenatal screening have been associated with a number of adverse perinatal and birth outcomes. However, it is not clear whether first trimester measurements of prenatal screening biomarkers are associated with subsequent risk of gestational diabetes mellitus (GDM). We aimed to systematically review and statistically summarize studies assessing the relationship between first trimester prenatal screening biomarker levels and GDM development. We comprehensively searched PubMed/MEDLINE, EMBASE, CINAHL, and Scopus (from inception through January 2018) and manually searched the reference lists of all relevant articles. We included original, published, observational studies examining the association of first trimester pregnancy associated plasma protein-A (PAPP-A) and/or free β-human chorionic gonadotropin (free β-hCG) levels with GDM diagnosis. Mean differences were calculated comparing PAPP-A and free β-hCG multiples of median (MoM) levels between women who developed GDM and those who did not and were subsequently pooled using two-sided random-effects models. Our meta-analysis of 13 studies on PAPP-A and nine studies on free β-hCG indicated that first trimester MoM levels for both biomarkers were lower in women who later developed GDM compared to women who remained normoglycemic throughout pregnancy (MD -0.17; 95% CI -0.24, -0.10; MD -0.04; 95% CI -0.07-0.01). There was no evidence for between-study heterogeneity among studies on free β-hCG (I2 = 0%). A high level of between-study heterogeneity was detected among the studies reporting on PAPP-A (I2 = 90%), but was reduced after stratifying by geographic location, biomarker assay method, and timing of GDM diagnosis. Our meta-analysis indicates that women who are diagnosed with GDM have lower first trimester levels of both PAPP-A and free β-hCG than women who remain normoglycemic throughout pregnancy. Further assessment of the predictive capacity of these biomarkers within large, diverse populations is needed.
Topics: Biomarkers; Chorionic Gonadotropin, beta Subunit, Human; Diabetes, Gestational; Female; Humans; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Prenatal Diagnosis
PubMed: 30048548
DOI: 10.1371/journal.pone.0201319 -
Contrast Media & Molecular Imaging 2018Our purpose was to provide data regarding relationships between F-FDG PET and histopathological parameters in lung cancer. (Meta-Analysis)
Meta-Analysis
Standardized Uptake Values Derived from F-FDG PET May Predict Lung Cancer Microvessel Density and Expression of KI 67, VEGF, and HIF-1 but Not Expression of Cyclin D1, PCNA, EGFR, PD L1, and p53.
BACKGROUND
Our purpose was to provide data regarding relationships between F-FDG PET and histopathological parameters in lung cancer.
METHODS
MEDLINE library was screened for associations between PET parameters and histopathological features in lung cancer up to December 2017. Only papers containing correlation coefficients between PET parameters and histopathological findings were acquired for the analysis. Overall, 40 publications were identified.
RESULTS
Associations between SUV and KI 67 were reported in 23 studies (1362 patients). The pooled correlation coefficient was 0.44. In 2 studies (180 patients), relationships between SUV and expression of cyclin D1 were analyzed (pooled correlation coefficient = 0.05). Correlation between SUV and HIF-1 was investigated in 3 studies (288 patients), and the pooled correlation coefficient was 0.42. In 5 studies (310 patients), associations between SUV and MVD were investigated (pooled correlation coefficient = 0.54). In 6 studies (305 patients), relationships between SUV and p53 were analyzed (pooled correlation coefficient = 0.30). In 6 studies (415 patients), associations between SUV and VEGF expression were investigated (pooled correlation coefficient = 0.44). In 5 studies (202 patients), associations between SUV and PCNA were investigated (pooled correlation coefficient = 0.32). In 3 studies (718 patients), associations between SUV and expression of PD L1 were analyzed (pooled correlation coefficient = 0.36). Finally, in 5 studies (409 patients), associations between SUV and EGFR were investigated (pooled correlation coefficient = 0.38).
CONCLUSION
SUV may predict microvessel density and expression of VEGF, KI 67, and HIF-1 in lung cancer.
Topics: B7-H1 Antigen; Cyclin D1; Fluorodeoxyglucose F18; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Ki-67 Antigen; Lung Neoplasms; Microvessels; Positron-Emission Tomography; Proliferating Cell Nuclear Antigen; Tumor Suppressor Protein p53
PubMed: 29983647
DOI: 10.1155/2018/9257929 -
Pharmacogenomics Jul 2018Smoking cessation treatment outcomes may be heavily influenced by genetic variations among smokers. Therefore, identifying specific variants that affect response to...
Smoking cessation treatment outcomes may be heavily influenced by genetic variations among smokers. Therefore, identifying specific variants that affect response to different pharmacotherapies is of major interest to the field. In the current study, we systematically review all studies published in or after the year 1990 which examined one or more gene-drug interactions for smoking cessation treatment. Out of 644 citations, 46 articles met the inclusion criteria for the systematic review. We summarize evidence on several genetic polymorphisms (CHRNA5-A3-B4, CYP2A6, DBH, CHRNA4, COMT, DRD2, DRD4 and CYP2B6) and their potential moderating pharamacotherarpy effects on patient cessation efficacy rates. These findings are promising and call for further research to demonstrate the effectiveness of genetic testing in personalizing treatment decision-making and improving outcome.
Topics: Cytochrome P-450 CYP2A6; Genetic Variation; Humans; Nerve Tissue Proteins; Nicotine; Pharmacogenetics; Receptors, Nicotinic; Smoking; Smoking Cessation; Tobacco Use Disorder
PubMed: 29914292
DOI: 10.2217/pgs-2018-0023 -
American Journal of Transplantation :... Dec 2018Acute graft-versus-host disease (GVHD) after liver transplant (LTx) is a rare complication with a high mortality rate. Recently, monoclonal antibody (mAb) treatment,...
Acute graft-versus-host disease (GVHD) after liver transplant (LTx) is a rare complication with a high mortality rate. Recently, monoclonal antibody (mAb) treatment, specifically with anti-interleukin 2 receptor antibodies (IL2RAb) and anti-tumor necrosis factor-α antibodies (TNFAb), has gained increasing interest. However, evidence is mostly limited to case reports and the efficacy remains unclear. Here, we describe 5 patients with LTx-associated GVHD from our center and provide the results of our systematic literature review to evaluate the potential therapeutic benefit of IL2RAb/TNFAb treatment. Of the combined population of 155 patients (5 in our center and 150 through systematic search), 24 were given mAb (15.5%)-4 with TNFAb (2.6%) and 17 with IL2RAb (11%) ("mAb group")-and compared with patients who received other treatments (referred to as "no-mAb group"). Two-sided Fisher exact tests revealed a better survival when comparing treatment with mAb versus no-mAb (11/24 vs 27/131; P = .018), TNFAb versus no-mAb (3/4 vs 27/131; P = .034), and IL2RAb versus no-mAb (8/17 vs 27/131; P = .029). This systematic review suggests a beneficial effect of mAb treatment and a promising role for TNFAb and IL2RAb as a first-line strategy to treat LTx-associated acute GVHD.
Topics: Adult; Aged; Antibodies, Monoclonal; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Graft vs Host Disease; Humans; Interleukin-2 Receptor alpha Subunit; Liver Transplantation; Male; Middle Aged; Postoperative Complications; Prognosis; Retrospective Studies; Risk Factors; Survival Rate; Tumor Necrosis Factor-alpha
PubMed: 29734503
DOI: 10.1111/ajt.14923 -
International Journal of Surgery... May 2018The relationship between expression of runt related transcription factor 3 (RUNX3) and clinicopathological parameters of the patients with gastric cancer (GC) is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The relationship between expression of runt related transcription factor 3 (RUNX3) and clinicopathological parameters of the patients with gastric cancer (GC) is controversial.
METHODS
The studies were retrieved from those already published essay in PubMed, EMBASE, Wan Fang, CNKI (China National Knowledge Infrastructure), the Cochrane Library and Google Scholar. All statistical tests in this meta-analysis were performed using Stata 10.0 software (Stata Corp, College Station, TX). A P value less than 0.05 was considered statistically significant.
RESULTS
A total of nine studies involving 796 patients were included in final meta-analysis. The pooled data showed that expression of RUNX3 was significant correlated with tumor's differentiation (OR = 0.387; 95%CI: 0.237-0.633; P = 0.000), depth of invasion (OR = 0.443; 95%CI: 0.273-0.717; P = 0.001), lymph node metastasis (OR = 0.394; 95%CI: 0.259-0.598; P = 0.000), distant metastasis (OR = 0.403; 95%CI: 0.213-0.764; P = 0.005) and TNM stage (OR = 0.461; 95%CI, 0.322-0.659; P = 0.000) in GC. Expression of RUNX3 was significant correlated with good overall survival (OS) [1-year OS (OR = 2.735; 95%CI: 1.966-3.806; P = 0.000), 3-year OS (OR = 4.782; 95%CI: 3.634-6.292; P = 0.000), 5-year OS (OR = 5.191; 95%CI: 3.775-7.138; P = 0.000]. However, RUNX3 was not correlated with gender (OR = 1.409; 95%CI: 0.986-2.014; P = 0.060).
CONCLUSION
RUNX3 expression correlates with tumor's differentiation, depth of invasion, lymph node metastasis, distant metastasis, TNM stage and OS of GC patients.
Topics: Core Binding Factor Alpha 3 Subunit; Humans; Lymphatic Metastasis; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Staging; Prognosis; Stomach Neoplasms
PubMed: 29578091
DOI: 10.1016/j.ijsu.2018.03.041 -
International Journal of Surgery... Mar 2018Cystic echinococcosis (CE) represents an increasing public health concern in many parts of the world, including the Middle East. The present study is the first... (Meta-Analysis)
Meta-Analysis Review
Cystic echinococcosis (CE) represents an increasing public health concern in many parts of the world, including the Middle East. The present study is the first systematic review and meta-analysis to assess the seroprevalence rate and population genetic structure of human CE in the eastern Mediterranean region. To estimate the population genetic structure, Echinococcus sequences of the cytochrome oxidase subunit 1 (cox1) gene isolated from countries from this geographical area were retrieved from the GenBank database. An electronic search for articles from 1990 until 2015 was performed using databases PubMed, ScienceDirect, and Scopus. A total of 53 articles reporting on CE seroprevalence and genotyping data met our eligibility criteria and were included in a meta-analysis. The overall CE seroprevalence rates in the general population and in individuals at high risk of infection were estimated using the random-effect model at 7.4% (95% CI = 4.8-10.6) and 10.7% (95% CI = 7.6-14.3), respectively. Risk factors including age group (P < 0.001), dog ownership (P = 0.03), residence area (P < 0.001), and educational level (P = 0.04) showed a statistically significant association with CE seroprevalence. A pairwise fixation index (Fst), used as an estimation of gene flow, suggested a moderate level of genetic differentiation between members of the E. granulosus sensu stricto (G1-G3) complex from Iranian and Turkish metapopulations (Fst = 0.171). The finding of common haplotypes may represent an ancestral transfer of alleles among populations probably during the early stages of animal domestication. The high CE seroprevalence rates found highlight the necessity of implementing appropriate public education for preventive and control strategies, particularly in individuals at high risk of infection; furthermore, our genetic findings reveal novel molecular data concerning microevolutionary events of Echinococcus isolates among Middle East countries.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Asian People; Cyclooxygenase 1; Dogs; Echinococcosis; Female; Genetic Variation; Genetics, Population; Genotype; Haplotypes; Humans; Iran; Male; Middle Aged; Middle East; Risk Factors; Seroepidemiologic Studies; Turkey; Young Adult
PubMed: 29367032
DOI: 10.1016/j.ijsu.2018.01.025 -
Journal of Cellular Biochemistry Jun 2018Breast cancer (BC) is the second most common cause of cancer-related deaths in women worldwide. The availability of reliable biomarkers of response/resistance to cancer... (Meta-Analysis)
Meta-Analysis
Breast cancer (BC) is the second most common cause of cancer-related deaths in women worldwide. The availability of reliable biomarkers of response/resistance to cancer treatments would benefit patients and clinicians allowing for a better selection of BC patients most likely to respond to a specific treatment. Phosphatidylinositol 3-kinase (PI3K) enzymes are involved in numerous cellular- functions and processes. The gene encoding for PI3K catalytic subunit p110α is mutated in 20-40% of BC. We performed a meta-analysis of the current literature on randomized clinical trials, investigating the role of PIK3CA mutational status as prognostic factor, and predictor of response to anti-cancer treatments. Overall 1929 cases were included. The pooled analysis confirmed that the presence of a PIK3CA mutation represents an independent negative prognostic factor (HR = 1.67, 95%CI: 1.15-2.43; P = 0.007) in BC, as previously reported. As PI3K signaling is also a result of other pathways' hyperactivation, further investigation of potential biomarkers able to predict likelihood of response to anti-PI3K/mTOR, anti-HER2, and other TKRs is warranted in future randomized clinical trials.
Topics: Breast Neoplasms; Class I Phosphatidylinositol 3-Kinases; Female; Humans; Neoplasm Proteins; Prognosis; Signal Transduction
PubMed: 29345357
DOI: 10.1002/jcb.26687 -
Redox Report : Communications in Free... Dec 2018p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative... (Review)
Review
BACKGROUND
p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis.
METHODS
A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases. Articles published in the English language between January 1, 1990 and March 1, 2017 were identified and isolated based on the analysis of p53 in skeletal muscle in both animal and cell culture models.
RESULTS
Literature was categorized according to the modality of imposed oxidative stress including exercise, diet modification, exogenous oxidizing agents, tissue manipulation, irradiation, and hypoxia. With low to moderate levels of oxidative stress, p53 is involved in activating pathways that increase time for cell repair, such as cell cycle arrest and autophagy, to enhance cell survival. However, with greater levels of stress intensity and duration, such as with irradiation, hypoxia, and oxidizing agents, the role of p53 switches to facilitate increased cellular stress levels by initiating DNA fragmentation to induce apoptosis, thereby preventing aberrant cell proliferation.
CONCLUSION
Current evidence confirms that p53 acts as a threshold regulator of cellular homeostasis. Therefore, within each modality, the intensity and duration are parameters of the oxidative stressor that must be analyzed to determine the role p53 plays in regulating signaling pathways to maintain cellular health and function in skeletal muscle.
ABBREVIATIONS
Acadl: acyl-CoA dehydrogenase, long chain; Acadm: acyl-CoA dehydrogenase, C-4 to C-12 straight chain; AIF: apoptosis-inducing factor; Akt: protein kinase B (PKB); AMPK: AMP-activated protein kinase; ATF-4: activating transcription factor 4; ATM: ATM serine/threonine kinase; Bax: BCL2 associated X, apoptosis regulator; Bcl-2: B cell Leukemia/Lymphoma 2 apoptosis regulator; Bhlhe40: basic helix-loop-helix family member e40; BH3: Borane; Bim: bcl-2 interacting mediator of cell death; Bok: Bcl-2 related ovarian killer; COX-IV: cytochrome c oxidase IV; cGMP: Cyclic guanosine monophosphate; c-myc: proto-oncogene protein; Cpt1b: carnitine palmitoyltransferase 1B; Dr5: death receptor 5; eNOS: endothelial nitric oxide synthase; ERK: extracellular regulated MAP kinase; Fas: Fas Cell surface death receptor; FDXR: Ferredoxin Reductase; FOXO3a: forkhead box O3; Gadd45a: growth arrest and DNA damage-inducible 45 alpha; GLS2: glutaminase 2; GLUT 1 and 4: glucose transporter 1(endothelial) and 4 (skeletal muscle); GSH: Glutathione; Hes1: hes family bHLH transcription factor 1; Hey1: hes related family bHLH transcription factor with YRPW motif 1; HIFI-α: hypoxia-inducible factor 1, α-subunit; HK2: Hexokinase 2; HSP70: Heat Shock Protein 70; HO: Hydrogen Peroxide; Id2: inhibitor of DNA-binding 2; IGF-1-BP3: Insulin-like growth factor binding protein 3; IL-1β: Interleukin 1 beta; iNOS: inducible nitric oxide synthase; IRS-1: Insulin receptor substrate 1; JNK: c-Jun N-terminal kinases; LY-83583: 6-anilino-5,8-quinolinedione; inhibitor of soluble guanylate cyclase and of cGMP production; Mdm 2/ 4: Mouse double minute 2 homolog (mouse) Mdm4 (humans); mtDNA: mitochondrial DNA; MURF1: Muscle RING-finger protein-1; MyoD: Myogenic differentiation 1; MyoG: myogenin; Nanog: Nanog homeobox; NF-kB: Nuclear factor-κB; NO: nitric oxide; NoxA: phorbol-12-myristate-13-acetate-induced protein 1 (Pmaip1); NRF-1: nuclear respiratory factor 1; Nrf2: Nuclear factor erythroid 2-related factor 2; P21: Cdkn1a cyclin-dependent kinase inhibitor 1A (P21); P38 MAPK: mitogen-activated protein kinases; p53R2: p53 inducible ribonucleotide reductase gene; P66Shc: src homology 2 domain-containing transforming protein C1; PERP: p53 apoptosis effector related to PMP-22; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PGM: phosphoglucomutase; PI3K: Phosphatidylinositol-4,5-bisphosphate 3-kinase; PKCβ: protein kinase c beta; PTEN: phosphatase and tensin homolog; PTIO: 2-phenyl-4, 4, 5, 5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) has been used as a nitric oxide (NO) scavenger; Puma: The p53 upregulated modulator of apoptosis; PW1: paternally expressed 3 (Peg3); RNS: Reactive nitrogen species; SIRT1: sirtuin 1; SCO2: cytochrome c oxidase assembly protein; SOD2: superoxide dismutase 2; Tfam: transcription factor A mitochondrial; TIGAR: Trp53 induced glycolysis repulatory phosphatase; TNF-a: tumor necrosis factor a; TRAF2: TNF receptor associated factor 2; TRAIL: type II transmembrane protein.
Topics: Animals; Diet; Exercise; Humans; Muscle, Skeletal; Oxidative Stress; Oxygen; Proto-Oncogene Mas; Radiation Injuries; Tumor Suppressor Protein p53
PubMed: 29298131
DOI: 10.1080/13510002.2017.1416773 -
Journal of Neurotrauma Apr 2021Accurate diagnosis of traumatic brain injury (TBI) is critical to effective management and intervention, but can be challenging in patients with mild TBI. A substantial... (Meta-Analysis)
Meta-Analysis
Blood-Based Protein Biomarkers for the Management of Traumatic Brain Injuries in Adults Presenting to Emergency Departments with Mild Brain Injury: A Living Systematic Review and Meta-Analysis.
Accurate diagnosis of traumatic brain injury (TBI) is critical to effective management and intervention, but can be challenging in patients with mild TBI. A substantial number of studies have reported the use of circulating biomarkers as signatures for TBI, capable of improving diagnostic accuracy and clinical decision making beyond current practice standards. We performed a systematic review and meta-analysis to comprehensively and critically evaluate the existing body of evidence for the use of blood protein biomarkers (S100 calcium binding protein B [S100B], glial fibrillary acidic protein [GFAP], neuron specific enolase [NSE], ubiquitin C-terminal hydrolase-L1 [UCH-L1]. tau, and neurofilament proteins) for diagnosis of intracranial lesions on CT following mild TBI. Effects of potential confounding factors and differential diagnostic performance of the included markers were explored. Further, appropriateness of study design, analysis, quality, and demonstration of clinical utility were assessed. Studies published up to October 2016 were identified through searches of MEDLINE, Embase, EBM Reviews, the Cochrane Library, World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP), and clinicaltrials.gov. Following screening of the identified articles, 26 were selected as relevant. We found that measurement of S100B can help informed decision making in the emergency department, possibly reducing resource use; however, there is insufficient evidence that any of the other markers is ready for clinical application. Our work pointed out serious problems in the design, analysis, and reporting of many of the studies, and identified substantial heterogeneity and research gaps. These findings emphasize the importance of methodologically rigorous studies focused on a biomarker's intended use, and defining standardized, validated, and reproducible approaches. The living nature of this systematic review, which will summarize key updated information as it becomes available, can inform and guide future implementation of biomarkers in the clinical arena.
Topics: Adult; Biomarkers; Blood Proteins; Brain Concussion; Brain Injuries, Traumatic; Disease Management; Emergency Service, Hospital; Glial Fibrillary Acidic Protein; Humans; Neurofilament Proteins; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit
PubMed: 29020853
DOI: 10.1089/neu.2017.5182