-
Cancer Treatment Reviews Jun 2024Gastric cancer (GC), known for its unfavorable prognosis, has been classified in four distinct molecular subtypes. These subtypes not only exhibit differences in their... (Review)
Review
BACKGROUND
Gastric cancer (GC), known for its unfavorable prognosis, has been classified in four distinct molecular subtypes. These subtypes not only exhibit differences in their genome and transcriptome but also in the composition of their tumor immune microenvironment. The microsatellite instable (MSI) and Epstein-Barr virus (EBV) positive GC subtypes show clear clinical benefits from immune checkpoint blockade, likely due to a neoantigen-driven and virus-driven antitumor immune response and high expression of immune checkpoint molecule PD-L1. However, even within these subtypes response to checkpoint inhibition is variable, which is potentially related to heterogeneity in the tumor immune microenvironment (TIME) and expression of co-inhibitory molecules. We conducted a systematic review to outline the current knowledge about the immunological features on the TIME of MSI and EBV + GCs.
METHODS
A systematic search was performed in PubMed, EMBASE and Cochrane Library. All articles from the year 1990 and onwards addressing immune features of gastric adenocarcinoma were reviewed and included based on predefined in- and exclusion criteria.
RESULTS
In total 5962 records were screened, of which 139 were included that reported immunological data on molecular GC subtypes. MSI and EBV + GCs were reported to have a more inflamed TIME compared to non-MSI and EBV- GC subtypes. Compared to microsatellite stable (MSS) tumors, MSI tumors were characterized by higher numbers of CD8 + and FoxP3 + T cells, and tumor infiltrating pro- and anti-inflammatory macrophages. HLA-deficiency was most common in MSI tumors compared to other molecular GC subtypes and associated with lower T and B cell infiltrates compared to HLA-proficient tumors. EBV + was associated with a high number of CD8 + T cells, Tregs, NK cells and macrophages. Expression of PD-L1, CTLA-4, Granzyme A and B, Perforin and interferon-gamma was enriched in EBV + tumors. Overall, MSI tumors harbored a more heterogeneous TIME in terms of immune cell composition and immune checkpoints compared to the EBV + tumors.
DISCUSSION AND CONCLUSION
MSI and EBV + GCs are highly Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration.; 2019pro-inflammatory immune cell populations. Although studies on the direct comparison of EBV + and MSI tumors are limited, EBV + tumors show less intra-subgroup heterogeneity compared to MSI tumors. More studies are needed to identify how Intra-subgroup heterogeneity impacts response to immunotherapy efficacy.
Topics: Humans; Stomach Neoplasms; Tumor Microenvironment; Epstein-Barr Virus Infections; DNA Mismatch Repair; Herpesvirus 4, Human; Microsatellite Instability
PubMed: 38669788
DOI: 10.1016/j.ctrv.2024.102737 -
Cancer Treatment Reviews Dec 2017The potential predictive value of genetic polymorphisms in ovarian cancer first-line treatment is inconsistently reported. We aimed to review ovarian cancer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The potential predictive value of genetic polymorphisms in ovarian cancer first-line treatment is inconsistently reported. We aimed to review ovarian cancer pharmacogenetic studies to update and summarize the available data and to provide directions for further research.
METHODS
A systematic review followed by a meta-analysis was conducted on cohort studies assessing the involvement of genetic polymorphisms in ovarian cancer first-line treatment response retrieved through a MEDLINE database search by November 2016. Studies were pooled and summary estimates and 95% confidence intervals (CI) were calculated using random or fixed-effects models as appropriate.
RESULTS
One hundred and forty-two studies gathering 106871 patients were included. Combined data suggested that GSTM1-null genotype patients have a lower risk of death compared to GSTM1-wt carriers, specifically in advanced stages (hazard ratio (HR), 0.68; 95% CI, 0.48-0.97) and when submitted to platinum-based chemotherapy (aHR, 0.61; 95% CI, 0.39-0.94). ERCC1 rs11615 and rs3212886 might have also a significant impact in treatment outcome (aHR, 0.67; 95% CI, 0.51-0.89; aHR, 1.28; 95% CI, 1.01-1.63, respectively). Moreover, ERCC2 rs13181 and rs1799793 showed a distinct ethnic behavior (Asians: aHR, 1.41; 95% CI, 0.80-2.49; aHR, 1.07; 95% CI, 0.62-1.86; Caucasians: aHR, 0.10; 95% CI, 0.01-0.96; aHR, 0.18; 95% CI, 0.05-0.68, respectively).
CONCLUSION(S)
The definition of integrative predictive models should encompass genetic information, especially regarding GSTM1 homozygous deletion. Justifying additional pharmacogenetic investigation are variants in ERCC1 and ERCC2, which highlight the DNA Repair ability to ovarian cancer prognosis. Further knowledge could aid to understand platinum-treatment failure and to tailor chemotherapy strategies.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cytoreduction Surgical Procedures; Female; Genetic Variation; Glutathione Transferase; Humans; Models, Genetic; Organoplatinum Compounds; Ovarian Neoplasms; Polymorphism, Single Nucleotide; Taxoids; Treatment Outcome
PubMed: 29100168
DOI: 10.1016/j.ctrv.2017.10.001 -
Phytotherapy Research : PTR May 2018Fuzheng Huayu (FZHY) capsule, a formulated traditional Chinese medicine product with 6 Chinese herbs, is widely used for HBV-related cirrhosis as an adjuvant treatment.... (Meta-Analysis)
Meta-Analysis Review
Fuzheng Huayu (FZHY) capsule, a formulated traditional Chinese medicine product with 6 Chinese herbs, is widely used for HBV-related cirrhosis as an adjuvant treatment. However, the efficacy of FZHY capsule for HBV-induced cirrhosis did not be comprehensively proved by systematic analysis. Our current analysis was aimed to assess the efficacy and safety of FZHY capsule by an evidence-based method. Databases, including China National Knowledge Infrastructure, Wangfang, VIP medicine information system, Pubmed, Embase, and Cochrane Library, were searched, and the randomized controlled trials of FZHY capsule were used for the treatment of HBV-associated liver cirrhosis. Meta-analysis was performed by Review Manager 5.3. The efficacy rate, alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), Procollagen III protein (PIIIP), hyaluronic acid (HA), laminin (LN), Collagen C Type IV (IV-C), Child-Pugh score, portal vein diameter, spleen thickness, HBeAg negative conversion rate, and HBV-DNA negative conversion rate were systematically assessed. The Cochrane Risk of Bias tool was used to evaluate the methodological quality of eligible studies. Nineteen studies with 1,769 patients were included in the meta-analysis. Compared to conventional treatment, FZHY capsule was effective by increasing the efficacy. FZHY capsule was more efficient in improving ALT, AST, TBIL, PIIIP, HA, LN, IV-C, Child-Pugh grading score, portal vein diameter, spleen thickness, and HBV-DNA negative conversion rate with no serious adverse reactions. Nevertheless, a variety of well-designed randomized controlled trials are needed to confirm these findings since small samples were applied in the previous studies.
Topics: Capsules; China; Combined Modality Therapy; Drugs, Chinese Herbal; Hepatitis B; Hepatitis B virus; Humans; Liver Cirrhosis; Treatment Outcome
PubMed: 29235181
DOI: 10.1002/ptr.6009 -
Andrology Jan 2024Infertility affects 186 million people worldwide, with male factors contributing to 50% of infertility cases. Semen analysis is a key for diagnosing male factor... (Review)
Review
BACKGROUND
Infertility affects 186 million people worldwide, with male factors contributing to 50% of infertility cases. Semen analysis is a key for diagnosing male factor infertility, but sperm parameters can be influenced by ejaculatory abstinence (EA) duration. Shortening or prolonging EA can impact on semen quality and assisted reproductive technology (ART) outcomes, but the optimal EA duration remains unclear, particularly for infertility patients.
OBJECTIVES
This study conducts a comprehensive meta-analysis to explore the impact of varying abstinence durations on semen quality and fertility outcomes.
METHODS
Three English database (PubMed, Embase, and Cochrane Central Register of Controlled Trials) as well as four Chinese database (China National Knowledge Infrastructure, Chinese Scientific Journals database, WanFang database, and Chinese Biomedical Literature database) were searched from 2000 to August 2023. The classical meta-analysis and "one-stage" dose-response meta-analysis were conducted to compare the associations of different abstinence durations (short-term abstinence vs. long-term abstinence) on semen quality in healthy adult and different type of infertile patients.
RESULTS
There were 85 eligible studies were finally included. The meta-analysis of volume (mean difference [MD] = -0.95 mL, 95% confidence interval [CI]: -1.16 to -0.74 mL), total sperm count (TSC) (MD = -102.45×10 , 95% CI: -117.98×10 to -86.91×10 ), sperm concentration (SC) (MD = -11.88×10 /mL, 95% CI: -18.96×10 /mL to -4.80×10 /mL), DNA fragmentation index (DFI) (MD = -2.37%, 95% CI: -4.73% to -0.01%) in healthy men showed a significant decrease with different abstinence durations (short-term abstinence vs. long-term abstinence). The meta-analysis of infertile men showed significant decrease in volume in various subgroups (MD range: -0.73 to -1.17 mL) with P < 0.01; TSC (MD = -61.93×10 , 95% CI: -88.84×10 to -35.01×10 ), SC (MD = -5.39×10 /mL, 95% CI: -9.97×10 to -0.81×10 /mL), DFI (MD = -5.63%, 95% CI: -10.19% to -1.06%) in unexplained infertility subgroup; significant increase in viability (MD = 6.14%, 95% CI: 3.61% to 8.68%) in the unexplained infertility subgroup. The dose-response meta-analysis showed that TSC in oligozoospermia showed a nonlinear increase (coefficient from 3.38 to -5.76, P from 0.02 to 0.22) and the truncation point was around the 4th to 5th abstinence day. The percentage of progressive motile sperm (PR) in asthenozoospermia showed a significant decrease (coefficient = -2.39, 95% CI: -4.28 to -0.50). For fertility outcomes of different ARTs, only the clinical pregnancy rate (CPR) in the intrauterine insemination (IUI) subgroup showed a significant decrease around the 3rd day (coefficient = 0.85, 95% CI: 0.75 to 0.97).
CONCLUSIONS
Short-term abstinence may be associated with limited improvements in semen quality in healthy men but could be more beneficial for infertile men, especially within the first 4 days of abstinence. Caution is urged in making definitive conclusions about the causal relationship between abstinence time and semen quality changes due to potential confounding and interactions.
PubMed: 38197853
DOI: 10.1111/andr.13583 -
Social Science & Medicine (1982) Mar 2021We systematically review the literature on social epigenetics, examining how empirical research to date has conceptualized and operationalized social determinants of... (Review)
Review
OBJECTIVE
We systematically review the literature on social epigenetics, examining how empirical research to date has conceptualized and operationalized social determinants of health (SDOH).
METHODS
Using comprehensive search procedures, we identified studies that consider the impact of SDOH on DNA methylation (DNAm), the most common measure of epigenetic change in research on human adult populations. We analyzed the studies to determine: 1) which populations and environments have been investigated in the literature; 2) how SDOH are defined and operationalized; 3) which SDOH have been linked to DNAm; and 4) what lessons from the SDOH literature can be better integrated into future studies exploring the social determinants of health and epigenetic outcomes.
RESULTS
We identified 67 studies, with 39 to 8397 participants. The SDOH most commonly considered were early life socioeconomic exposures and early life trauma or mental health. Our review highlights four broad challenges: a) high dependence on convenience sampling, b) limited racial/ethnic, and geographic diversity in sampling frames, c) overreliance on individual sociodemographic characteristics as proxies for broader stratification processes, and d) a focus on downstream social determinants of health and individualized experiences with social stressors.
CONCLUSIONS
Future social epigenetics research should prioritize larger, more diverse and representative population-based samples and employ the SDOH framework to better inform the conceptualization of research questions and interpretation of findings. In particular, the simplified depiction of race/ethnicity, gender, and socioeconomic status as individual-level characteristics should be updated with an explicit acknowledgement that these characteristics are more accurately interpreted as cues used by society to differentiate subpopulations. Social epigenetics research can then more clearly elucidate the biological consequences of these social exposures for patterns of gene expression, subsequent disease etiology, and health inequities.
Topics: Adult; Epigenesis, Genetic; Humans; Social Determinants of Health
PubMed: 33610974
DOI: 10.1016/j.socscimed.2021.113738 -
Head and Neck Pathology Dec 2023The BRAF p.V600E genetic variant facilitates the pathogenesis of various tumors by triggering tumor proliferation and progression. The aim of this study was to analyze... (Review)
Review
BACKGROUND
The BRAF p.V600E genetic variant facilitates the pathogenesis of various tumors by triggering tumor proliferation and progression. The aim of this study was to analyze the prevalence of BRAF p.V600E in benign mixed epithelial and mesenchymal and malignant odontogenic tumors. In addition, we discussed the different detection methods used to assess for aberrant BRAF.
METHODS
This systematic review followed the PRISMA guidelines and was registered in Prospero (CRD42023445689). A comprehensive search of the PubMed/MEDLINE, Scopus, Web of Science, and Embase electronic databases was performed to answer the question "What is the prevalence of the BRAF p.V600E mutation in benign mixed and malignant odontogenic tumors?" The methodological quality of the selected studies was assessed using the JBI's Critical Appraisal Tool.
RESULTS
Initially, 387 records were identified, but only 11 articles met the inclusion criteria. A total of 70 patients with benign mixed epithelial and mesenchymal odontogenic tumors and 63 with malignant odontogenic tumors were included in the analysis. We found that the BRAF p.V600E mutation had a prevalence of 31.42% in mixed tumors and 26.98% in malignant odontogenic tumors. Moreover, immunohistochemistry showed high concordance with DNA-based molecular methods.
CONCLUSION
In general, the BRAF p.V600E variant exhibited a prominent prevalence in mixed and malignant odontogenic tumors. However, most of the findings are based on small cohorts of patients and further studies with larger cohorts are needed.
Topics: Humans; Mutation; Proto-Oncogene Proteins B-raf; Prevalence; Odontogenic Tumors; Mouth Neoplasms
PubMed: 38057461
DOI: 10.1007/s12105-023-01601-6 -
Frontiers in Neuroendocrinology Apr 2022Adverse childhood experiences (ACEs) may leave long-lasting neurobiological scars, increasing the risk of developing mental disorders in later life. However, no review... (Review)
Review
Adverse childhood experiences (ACEs) may leave long-lasting neurobiological scars, increasing the risk of developing mental disorders in later life. However, no review has comprehensively integrated existing evidence across the fields: hypothalamic-pituitary-adrenal axis, immune/inflammatory system, neuroimaging, and genetics/epigenetics. We thus systematically reviewed previous meta-analyses towards an integrative account of ACE-related neurobiological alterations. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, a total of 27 meta-analyses until October 2021 were identified. This review found that individuals with ACEs possess blunted cortisol response to psychosocial stressors, low-grade inflammation evinced by increased C-reactive protein levels, exaggerated amygdalar response to emotionally negative information, and diminished hippocampal gray matter volume. Importantly, these alterations were consistently observed in those with and without psychiatric diagnosis. These findings were integrated and discussed in a schematic model of ACE-related neurobiological alterations. Future longitudinal research based on multidisciplinary approach is imperative for ACE-related mental disorders' prevention and treatment.
Topics: Adverse Childhood Experiences; Humans; Hypothalamo-Hypophyseal System; Mental Disorders; Pituitary-Adrenal System; Stress, Psychological
PubMed: 35331780
DOI: 10.1016/j.yfrne.2022.100994 -
Scientific Reports Apr 2022The comprehensive effect size of several commercial vaccines and vaccine candidates against edema disease (ED) has not been evaluated to date. To integrate the... (Meta-Analysis)
Meta-Analysis
The comprehensive effect size of several commercial vaccines and vaccine candidates against edema disease (ED) has not been evaluated to date. To integrate the effectiveness of ED vaccines reported so far and to compare and evaluate the posterior-effect estimates of each vaccine type with network models, we identified eligible studies (n = 12) from the electronic databases using specified search strings. Data for dichotomous outcomes (i.e., mortality and clinical symptoms) and continuous outcomes (i.e., fecal shedding and average daily gain) were extracted and analyzed. Conventional meta-analysis shows that, compared with that in non-vaccinated pigs, vaccinated animals are likely to show reduced mortality (OR = 0.07) and clinical signs of ED (OR = 0.11), and increased productivity (SMD = 0.73). Although reduced fecal shedding (SMD = - 1.29) was observed in vaccinated pigs, this could not be fully determined on insufficient grounds. In contrast to mortality and clinical symptoms, fecal shedding (I = 88%) and average daily gain (I = 85%) showed immense heterogeneity, which was attributed to the small sample size and vaccination route, respectively. According to the Bayesian network meta-analysis, the plasmid-based DNA vaccine demonstrated a better effect for all outcomes compared to other types of vaccines. However, these findings should be carefully interpreted with consideration to potential mediators, insufficient data, and inconsistent network models.
Topics: Animals; Bayes Theorem; Edema; Edema Disease of Swine; Escherichia coli Infections; Network Meta-Analysis; Shiga-Toxigenic Escherichia coli; Swine; Vaccine Efficacy
PubMed: 35440612
DOI: 10.1038/s41598-022-10439-x -
Scientific Reports Oct 2022The association between the expression of Lysyl oxidase (LOX) and its clinicopathological parameters and prognosis in patients with gastric cancer (GC) is still... (Meta-Analysis)
Meta-Analysis
The association between the expression of Lysyl oxidase (LOX) and its clinicopathological parameters and prognosis in patients with gastric cancer (GC) is still disputed. We performed this meta-analysis and bioinformatics analysis to clarify the relationship between the expression and methylation level of LOX with its clinicopathological parameters and prognostic value. We applied odds ratios with a 95% confidence interval to study the associations between LOX expression and clinicopathological parameters and overall survival (OS) in GC patients. In addition, association analysis of promoter methylation levels and expression of LOX with its prognostic value was performed using the Cancer Genome Atlas (TCGA) and four Gene Expression Omnibus (GEO) datasets. The PRISMA 2020 checklist was used to guide the data extraction and analysis. This meta-analysis includes seven clinical studies with a total of 1435 GC patients. LOX expression was related to lymph node metastasis and tumor distant metastasis in GC patients, but not to gender, tumor differentiation, Lauren classification, or tumor depth of invasion. Patients with GC grouped in high-expression of LOX had a much worse OS than those in low-expression. In addition, TCGA and four GEO datasets with 1279 samples were included in the bioinformatics analysis. The bioinformatics analysis showed that patients with high LOX levels had poor OS; low levels of methylation at some cg sites in the LOX gene were strongly related to poor OS and PFS; and methylation levels of LOX are negatively correlated with advanced tumor stage. The conclusion from comprehensive DNA methylation and gene expression analysis supports LOX as a specific diagnostic and prognosis biomarker in GC. LOX expression was related to lymph node metastasis, tumor distant metastasis and poor prognosis in GC. Low methylation levels were related to advanced tumor stage and poor prognosis in GC. Integrative analysis supports LOX as a specific diagnostic and prognosis biomarker in GC.
Topics: Biomarkers; Biomarkers, Tumor; Computational Biology; Humans; Lymphatic Metastasis; Prognosis; Protein-Lysine 6-Oxidase; Stomach Neoplasms
PubMed: 36202905
DOI: 10.1038/s41598-022-21402-1 -
PeerJ 2022This study aimed to assess the diagnostic performance of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC). (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aimed to assess the diagnostic performance of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
We enrolled all relevant studies published up to 5 January 2022. Three primary subgroups were investigated: qualitative or quantitative ctDNA analyses, combined alpha-fetoprotein (AFP), and ctDNA assay. In addition to the three primary subgroups, we also evaluated the diagnostic value of methylated SEPTIN9 (mSEPT9), which has been studied extensively in the diagnosis of hepatocellular carcinoma. After a search based on four primary databases, we used a bivariate linear mixed model to analyze the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). We also plotted hierarchical summary receiver operating characteristics (HSROC) and utilized lambda as well as the area under the curve (AUC) to create summary receiver operating characteristic (SROC) curves to estimate the diagnostic value of ctDNA.
RESULTS
A total of 59 qualified articles with 9,766 subjects were incorporated into our meta-analysis. The integrated SEN, SPE, and DOR in the qualitative studies were 0.50 (95% CI [0.43-0.56]), 0.90 (95% CI [0.86-0.93]), and 8.72 (95% CI [6.18-12.32]), respectively, yielding an AUC of 0.78 and lambda of 1.93 (95% CI [1.56-2.33]). For quantitative studies, the corresponding values were 0.69 (95% CI [0.63-0.74]), 0.84 (95% CI [0.77-0.89]), 11.88 (95% CI [7.78-18.12]), 0.81, and 2.32 (95% CI [1.96-2.69]), respectively. Six studies were included to evaluate the SETP9 methylation, which yielded an AUC of 0.86, a SEN of 0.80 (95% CI [0.71-0.87]), and a SPE of 0.77 (95% CI [0.68-0.85]). Likewise, ctDNA concentration yielded an AUC of 0.73, with a SEN of 0.63 (95% CI [0.56-0.70]) and a SPE of 0.86 (95% CI [0.74-0.93]). AFP combined with ctDNA assay resulted in an AUC of 0.89, with a SEN of 0.82 (95% CI [0.77-0.86]) and a SPE of 0.84 (95% CI [0.76-0.90]).
CONCLUSION
This study shows that circulating tumor DNA, particularly mSEPT9, shows promising diagnostic potential in HCC; however, it is not enough to diagnose HCC independently, and ctDNA combined with conventional assays such as AFP can effectively improve diagnostic performance.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Circulating Tumor DNA; ROC Curve
PubMed: 36348665
DOI: 10.7717/peerj.14303