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Frontiers in Neuroscience 2022Although some previous studies have indicated that extracellular vesicles (EVs) secreted from miRNA-modified mesenchymal stem cells (MSCs) may be more effective as...
BACKGROUND
Although some previous studies have indicated that extracellular vesicles (EVs) secreted from miRNA-modified mesenchymal stem cells (MSCs) may be more effective as compared with control EVs in the treatment of rats with spinal cord injuries (SCI), the efficacy of this treatment modality remains controversial.
OBJECTIVES
The current study comprehensively evaluated the efficacy of different administered doses of EVs, including miRNA-overexpressing MSCs-derived EVs, among SCI rats. The efficacy of EVs' treatment was evaluated in different SCI models to provide evidence for preclinical trials.
METHODS
We extensively searched the following databases to identify relevant studies: PubMed, Embase, Scopus, The Cochrane Library, and Web of Science (from inception to July 20, 2022). Two trained investigators independently screened literature, extracted the data, and evaluated literature quality.
RESULTS
Thirteen studies were included in this network meta-analysis. The results demonstrated that miRNA-overexpressing MSCs-derived EVs (100 and 200 μg of total protein of EVs) significantly improved hind limb motor function in rats at early stages of SCI (i.e., at 3 days after injury) as compared with EVs (100 and 200 μg of total protein of EVs, respectively). However, in the middle and late stages (14 and 28 days), there were no statistically significant differences between EVs with 200 μg dosages and miRNA-loaded EVs with 100 μg dosages. In the late stages (28 days), there were no statistically significant differences between EVs with 100 μg dosages and miRNA-loaded EVs with 200 μg dosages. We found that miRNA-overexpressing MSCs-derived EVs significantly improved motor function among early-stage SCI rats in a compression and contusion model (3 days) as compared with MSCs-derived EVs and miRNA-overexpressing MSCs-derived EVs likewise significantly improved motor function among SCI rats in a contusion model at middle and late stages (14 and 28 days).
CONCLUSION
Our results suggest that miRNA-overexpressing MSCs-derived EVs (200 μg of total protein of EVs) may be the best choice for the effective treatment of SCI, and miRNA-overexpressing MSCs-derived EVs may likewise be the best choice for treating contusions. However, there are some risks of bias in our included studies, and the mechanisms underlying the efficacy of EVs remain unclear. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=282051, identifier: CRD42021282051.
PubMed: 36278023
DOI: 10.3389/fnins.2022.989295 -
International Journal of Molecular... Oct 2022The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for... (Review)
Review
The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for periodontitis as a low-grade inflammatory disease with systemic effects but also as an important source of potentially valuable clinical biomarkers of its systemic effects and susceptibility to other inflammatory conditions. Thus, we aimed to identify relevant genes tested as epigenetic systemic biomarkers in patients with periodontitis, based on the DNA methylation patterns and RNA expression profiles in peripheral immune cells. A detailed protocol was designed following the Preferred Reporting Items for Systematic Review and Meta-analysis -PRISMA guideline. Only cross-sectional and case-control studies that reported potential systemic biomarkers of periodontitis in peripheral immune cell types were included. DNA methylation was analyzed in leukocytes, and gene expression was in polymorphonuclear and mononuclear cells. Hypermethylation was found in TLR regulators genes: , , , , , , and in early stages of periodontitis, while advanced stages presented hypomethylation of these genes. , , , and genes were differentially expressed in lymphocytes and monocytes of subjects with poorly controlled diabetes mellitus, dyslipidemia, and periodontitis in comparison with controls. The gene was differentially overexpressed in periodontitis and dyslipidemia. Peripheral blood neutrophils in periodontitis showed differential expression in 163 genes. Periodontitis showed an increase in ceruloplasmin gene expression in polymorphonuclears in comparison with controls. Several genes highlight the role of the epigenetics of peripheral inflammatory cells in periodontitis that could be explored in blood as a source of biomarkers for routine testing.
Topics: Biomarkers; Ceruloplasmin; Cross-Sectional Studies; DNA Methylation; Dyslipidemias; Gene Expression; Humans; Myeloid Differentiation Factor 88; Periodontitis; RNA
PubMed: 36233348
DOI: 10.3390/ijms231912042 -
Revista Espanola de Enfermedades... Mar 2024colorectal cancer (CRC) is the most common carcinoma worldwide, but a lack of effective prognostic markers limits clinical diagnosis and treatment. Yes-associated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
colorectal cancer (CRC) is the most common carcinoma worldwide, but a lack of effective prognostic markers limits clinical diagnosis and treatment. Yes-associated protein 1 (YAP1) is an effector of the HIPPO-pathway, which plays a critical role in cancer development and prognosis, including CRC. However, previous reports have suggested that it plays a dual role in CRC.
METHODS
a meta-analysis using RevMan 5.4 and Stata 14.0 was performed to evaluate the relationship between YAP1 and clinical outcomes of CRC, after searching for eligible studies in the PubMed, Web of Science and Embase databases. Online datasets GEPIA and LOGpc were also used to calculate survival results and for comparison with the meta-analysis results. Besides, "DESeq" packages were used for the expression analysis of YAP1 from the TCGA dataset.
RESULTS
YAP1 was overexpressed in the cancer tissues when compared to normal tissues in patients with CRC from the TCGA database (p = 0.000164) and GEPIA database. A total of 10 studies involving 2305 patients from the literature were selected. Pooled HR indicated that overexpression of YAP1 was associated with poor clinical outcomes (HR = 1.70, 95 % CI: 1.28-2.26, p = 0.0003). Subgroup analysis showed a clear correlation between overexpression of YAP1 and worse survival rate in Chinese patients (HR = 1.94, 95 % CI: 1.40-2.69, p = 0.0001), nuclear YAP1 overexpression (HR = 2.07, 95 % CI: 1.29-3.31, p = 0.003), 60 months of follow-up (HR = 1.89, 95 % CI: 1.30-2.73, p = 0.0008), IHC test (HR = 1.65, 95 % CI: 1.17-2.33, p = 0.005), IHC combined with other tests (HR = 1.77, 95 % CI: 1.13-2.77, p = 0.01) and multivariate analysis (HR = 1.70, 95 % CI: 1.24-2.31, p = 0.0009). Nevertheless, disease-free survival (DFS) showed no significant results in the patients with CRC in our meta-analysis (HR = 1.38, 95 % CI: 0.51-3.75, p = 0.52) as well as in the GEPIA and LOGpc databases. Meanwhile, YAP1 overexpression was also significantly associated with worse overall survival (OS) in GSE17536, GSE40967, GSE29623 and GSE71187.
CONCLUSION
YAP1 overexpression is common in CRC tissues. Overexpression of YAP1 in CRC patients, particularly in the nucleus, might be related to shorter OS, maybe in the early stages. YAP1 could serve as a potential predictor of poor prognosis in CRC.
Topics: Humans; Prognosis; YAP-Signaling Proteins; Carcinoma; Databases, Factual; Colorectal Neoplasms
PubMed: 36177818
DOI: 10.17235/reed.2022.8472/2021 -
Tumour Biology : the Journal of the... 2022Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis, and chemotherapy drug resistance in cancers. Here we conducted a systematic review and meta-analysis to determine its prognostic value and clinicopathological features in breast cancer and some other malignancies.
MATERIALS AND METHODS
PubMed, Scopus, Cochrane Library, Web of Science, and EMBASE were searched up to Feb 2022 for the association of A3B with breast, ovarian, gastrointestinal and lung cancers. The pooled hazard ratios with 95% confidence interval (CI) were evaluated to assess disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) in cancers under study.
RESULTS
Over 3700 patients were included in this meta-survey. Elevated levels of A3B were significantly related to low OS (pooled HR = 1.30; 95% CI:1.09-1.55, P < 0.01), poor DFS (pooled HR = 1.66; 95% CI:1.17-2.35, P < 0.01) and poor RFS (HR = 1.51, 95% CI:1.11-2.04, P = 0.01). Subgroup analysis revealed that high A3B expression was associated with poor OS in lung (HR = 1.85, 95% CI: 1.40-2.45), and breast cancers (HR = 1.38, 95% CI: 1.00-1.89). High expression of A3B did not display any significant association with clinicopathologic features.
CONCLUSION
APOBEC3B overexpression is related to poor OS, DFS and RFS only in some cancer types and no generalized role could be predicted for all cancers.
Topics: Breast Neoplasms; Cytidine Deaminase; Disease-Free Survival; Female; Humans; Lung Neoplasms; Minor Histocompatibility Antigens; Proportional Hazards Models
PubMed: 36093650
DOI: 10.3233/TUB-211577 -
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 -
International Journal of Molecular... Aug 2022Background: Glioblastoma (GBM) is a highly aggressive cancer with poor prognosis that needs better treatment modalities. Moreover, there is a lack of reliable biomarkers... (Meta-Analysis)
Meta-Analysis Review
Background: Glioblastoma (GBM) is a highly aggressive cancer with poor prognosis that needs better treatment modalities. Moreover, there is a lack of reliable biomarkers to predict the response and outcome of current or newly designed therapies. While several molecular markers have been proposed as potential biomarkers for GBM, their uptake into clinical settings is slow and impeded by marker heterogeneity. Detailed assessment of prognostic and predictive value for biomarkers in well-defined clinical trial settings, if available, is scattered throughout the literature. Here we conducted a systematic review and meta-analysis to evaluate the prognostic and predictive significance of clinically relevant molecular biomarkers in GBM patients. Material and methods: A comprehensive literature search was conducted to retrieve publications from 3 databases (Pubmed, Cochrane and Embase) from January 2010 to December 2021, using specific terms. The combined hazard ratios (HR) and confidence intervals (95% CI) were used to evaluate the association of biomarkers with overall survival (OS) in GBM patients. Results: Twenty-six out of 1831 screened articles were included in this review. Nineteen articles were included in the meta-analyses, and 7 articles were quantitatively summarised. Fourteen studies with 1231 GBM patients showed a significant association of MGMT methylation with better OS with the pooled HR of 1.66 (95% CI 1.32−2.09, p < 0.0001, random effect). Five studies including 541 GBM patients analysed for the prognostic significance of IDH1 mutation showed significantly better OS in patients with IDH1 mutation with a pooled HR of 2.37 (95% CI 1.81−3.12; p < 0.00001]. Meta-analysis performed on 5 studies including 575 GBM patients presenting with either amplification or high expression of EGFR gene did not reveal any prognostic significance with a pooled HR of 1.31 (95% CI 0.96−1.79; p = 0.08). Conclusions: MGMT promoter methylation and IDH1 mutation are significantly associated with better OS in GBM patients. No significant associations were found between EGFR amplification or overexpression with OS.
Topics: Biomarkers; Biomarkers, Tumor; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Humans; Tumor Suppressor Proteins
PubMed: 36012105
DOI: 10.3390/ijms23168835 -
Ginekologia Polska 2022Cervical cancer is one of the most common cancers in women worldwide. Although mortality has declined over the past 30 years in high-income areas, it remains a problem... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Cervical cancer is one of the most common cancers in women worldwide. Although mortality has declined over the past 30 years in high-income areas, it remains a problem in several countries. Given that the prognosis of patients with recurrent or metastatic disease is poor, it is necessary to identify valuable predictive indicators to estimate survival outcomes in patients with cervical cancer.
MATERIAL AND METHODS
We searched electronic databases such as PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Central Register of Controlled Trials, and investigated the relationship between Programmed death-ligand 1(PD-L1) expression and prognosis. Chi squared tests and I2 were utilized to assess study heterogeneity, and publication bias was estimated using Begg's funnel plot and Egger linear regression test.
RESULTS
Thirteen eligible studies with 1422 patients were included. Generally, high PD-L1 expression was conclusively associated with poor overall survival (OS) (HR: 1.31; 95% CI 1.03-1.66, p = 0.025). However, PD-L1 expression demonstrated no association with progression-free survival (HR: 0.93; 0.73-1.19, p = 0.57). High PD-L1 expression with a sample size over 100 indicated a shorter OS (HR: 1.51; 95% CI 1.13-2.01). High expression of PD-L1 in Asians represented a lower OS (HR: 1.52; 1.14-2.03). Overexpression of PD-L1 in tumor cells (HR: 1.57; 1.29-2.10) and tumor-infiltrating immune cells (HR: 1.75; 1.02-2.99) predicted poor OS. High PD-L1 expression (HR: 4.04; 2.58-6.31) showed a lower effect on OS with a cut-off value of 5%.
CONCLUSIONS
Our results indicate that high PD-L1 expression could be a valuable biomarker for predicting clinical outcomes in patients with cervical cancer.
Topics: Humans; Female; B7-H1 Antigen; Uterine Cervical Neoplasms; Biomarkers; Prognosis
PubMed: 35984342
DOI: 10.5603/GP.a2022.0071 -
Cancers Jul 2022The aim of this systematic review and meta-analysis was to evaluate the current evidence on the prognostic and clinicopathological significance value of telomerase... (Review)
Review
The aim of this systematic review and meta-analysis was to evaluate the current evidence on the prognostic and clinicopathological significance value of telomerase reverse transcriptase (TERT) upregulation in patients with oral squamous cell carcinoma (OSCC). PubMed, Embase, Web of Science, and Scopus were searched for studies published before April 2022, not restricted by date or publication language. The methodological quality of primary-level studies was critically assessed using the Quality in Prognosis Studies (QUIPS) tool. We carried out meta-analyses, explored heterogeneity and its sources, and performed subgroup, meta-regression, sensitivity, and small-study effects analyses. Twenty-one studies (1698 patients) met inclusion criteria. TERT protein overexpression was significantly associated with worse overall survival (hazard ratio [HR] = 3.01, 95% CI = 1.70−5.35, p < 0.001), disease-free survival (HR = 4.03, 95% CI = 1.80−9.05, p = 0.001), and higher histological grade OSCC (odds ratio [OR] = 3.20, 95% CI = 1.83−5.62, p < 0.001). These large effect sizes were consistently obtained by homogeneous subgroups (p > 0.10, I2 = 0.0, respectively), which reflects a high quality of evidence. On the other hand, TERT gene mutations obtained constantly nonsignificant null effect sizes for all outcomes investigated, evidencing no prognostic or clinicopathological value. In conclusion, our findings indicate that TERT upregulation is a prognostic indicator of poor survival in oral cancer. Our findings support the immunohistochemical assessment of TERT overexpression, which could probably be incorporated into the prognostic evaluation of OSCC.
PubMed: 35954336
DOI: 10.3390/cancers14153673 -
Cancers Jul 2022Neuropilin-1 (NRP1) is a transmembrane protein involved in numerous cellular functions which has had increasing interest from cancer researchers. Liver cancer and... (Review)
Review
Neuropilin-1 (NRP1) is a transmembrane protein involved in numerous cellular functions which has had increasing interest from cancer researchers. Liver cancer and colorectal cancer (CRC) are two of the most frequent and deadly tumors with a complex pharmacological framework. Here, we assessed the prognostic, diagnostic and clinicopathological value of NRP1 in liver cancer and CRC patients. We searched PubMed, Scopus, Web of Science, Embase and Cochrane Library databases for articles evaluating the NRP1 correlation with survival parameters, tumor development or clinicopathological features. Hazard ratios and odds ratios with 95% confidence intervals were extracted or estimated by Parmar method and pooled to evaluate the overall effect size with STATA 16 software. Heterogeneity was analyzed by chi-square-based Q test and I statistic, along with meta-regression and subgroup analysis, and publication bias was assessed by funnel plot asymmetry and Egger's test. The study protocol was registered in PROSPERO (CRD42022307062). NRP1 overexpression was significantly correlated with lower survival in liver cancer patients and with tumor development in hepatocarcinoma patients, and was strongly correlated with an increased risk of vascular invasion in liver cancer and metastasis in CRC and liver tumors. These results support the role of NRP1 as a potential and useful biomarker in both types of cancer.
PubMed: 35884516
DOI: 10.3390/cancers14143455 -
Medicine Jul 2022Macrophage colony-stimulating factor (M-CSF) overexpression in plasma levels serves as a useful predictor of carcinogenesis and poor prognosis. Thus, we aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Macrophage colony-stimulating factor (M-CSF) overexpression in plasma levels serves as a useful predictor of carcinogenesis and poor prognosis. Thus, we aimed to investigate the diagnostic performance of M-CSF for cervical cancer.
METHODS
A comprehensive search of eligible studies was performed in PubMed/MEDLINE, Cochrane Library, Google Scholar, Scopus, Web of Science, and EMBASE published until October 2021. For statistical analysis, Meta-disc software is used. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, 95% confidence interval (CI), and the area under the curve were estimated. A P value <.05 was considered statistically significant.
RESULTS
A total of 5 studies were included in this systematic review and meta-analysis. The result showed that the pooled sensitivity and specificity of M-CSF to diagnose cervical cancer were 70% (95% CI: 66%-74%) and 84% (95% CI: 80%-88%), respectively. The summary positive likelihood ratio and negative likelihood ratio were 4.41 (95% CI: 2.86-6.82) and 0.36 (95% CI: 0.29-0.45), respectively. The area under the curve of the summary receiver operating characteristic curve was 0.86 (95% CI: 0.83-0.88), indicating the excellent diagnostic performance of M-CSF for cervical cancer.
CONCLUSIONS
The results of this study showed that M-CSF has diagnostic value for the early detection of cervical cancer. As a result, M-CSF can be utilized in conjunction with existing test platforms to diagnose cervical cancer.
Topics: Female; Humans; Macrophage Colony-Stimulating Factor; Odds Ratio; ROC Curve; Sensitivity and Specificity; Uterine Cervical Neoplasms
PubMed: 35839008
DOI: 10.1097/MD.0000000000029538