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Cancers May 2022In this systematic review, we foresee what could be the approved scenario in the next few years for CAR-T cell therapies directed against hematological and solid tumor... (Review)
Review
In this systematic review, we foresee what could be the approved scenario in the next few years for CAR-T cell therapies directed against hematological and solid tumor malignancies. China and the USA are the leading regions in numbers of clinical studies involving CAR-T. Hematological antigens CD19 and BCMA are the most targeted, followed by mesothelin, GPC3, CEA, MUC1, HER2, and EGFR for solid tumors. Most CAR constructs are second-generation, although third and fourth generations are being largely explored. Moreover, the benefit of combining CAR-T treatment with immune checkpoint inhibitors and other drugs is also being assessed. Data regarding product formulation and administration, such as cell phenotype, transfection technique, and cell dosage, are scarce and could not be retrieved. Better tracking of trials' status and results on the ClinicalTrials.gov database should aid in a more concise and general view of the ongoing clinical trials involving CAR-T cell therapy.
PubMed: 35681646
DOI: 10.3390/cancers14112667 -
Diagnostics (Basel, Switzerland) Sep 2022In previous studies, non-invasive diagnostic biomarkers showed great benefit in the early-stage diagnosis of malignant pleural mesothelioma (MPM). However, the accuracy... (Review)
Review
In previous studies, non-invasive diagnostic biomarkers showed great benefit in the early-stage diagnosis of malignant pleural mesothelioma (MPM). However, the accuracy of different biomarkers was controversial. In this study, meta-analysis and bioinformatics analysis were conducted to compare the accuracy of the following three biomarkers and explore the relationship between the gene expression levels and MPM. A systematic search of meta-analysis was conducted using PubMed, EMBASE and Cochrane Library to identify relevant studies from the inception to March 2021. QUADAS-2 for Quality Assessment of Diagnostic Accuracy Studies was used to evaluate the quality of eligible studies. The meta-analysis was performed utilizing Stata 15.0 and Review Manager 5.4 software. The meta-analysis results showed that 31 studies that involved 8750 participants were included. The pooled sensitivity and specificity (SPE) were 0.90 (95% CI: 0.74, 0.97) and 0.91 (95% CI: 0.84, 0.95) for Fibulin-3, 0.66 (95% CI, 0.51-0.78) and 0.91 (95% CI, 0.82-0.96) for mesothelin (MSLN), 0.68 (95% CI: 0.63,0.73) and 0.86 (95% CI: 0.82,0.90) for soluble mesothelin-related peptides (SMRP), and 0.74 (95% CI, 0.66-0.80) and 0.89 (95% CI, 0.85-0.91) for MSLN + SMRP + Fibulin-3. Compared with the other two biomarkers, Fibulin-3 may be more appropriate to be one of the indicators for combined diagnosis. Bioinformatics analysis showed that the low expression level of the MSLN gene was significantly related to longer survival time and better prognosis of MPM patients. However, considering the limitation in the quality and sample size of the included research, further studies are required.
PubMed: 36140611
DOI: 10.3390/diagnostics12092210 -
HPB : the Official Journal of the... Aug 2016Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential... (Review)
Review
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential prognostic biomarkers to facilitate validation studies and clinical application.
METHODS
A systematic review was performed (2004-2014) according to PRISMA guidelines. Studies were ranked using REMARK criteria and the following outcomes were examined: overall/disease free survival, nodal involvement, tumour characteristics, metastasis, recurrence and resectability.
RESULTS
256 biomarkers were identified in 158 studies. 171 biomarkers were assessed with respect to overall survival: urokinase-type plasminogen activator receptor, atypical protein kinase C and HSP27 ranked the highest. 33 biomarkers were assessed for disease free survival: CD24 and S100A4 were the highest ranking. 17 biomarkers were identified for lymph node involvement: Smad4/Dpc4 and FOXC1 ranked highest. 13 biomarkers were examined for tumour grade: mesothelin and EGFR were the highest ranking biomarkers. 10 biomarkers were identified for metastasis: p16 and sCD40L were the highest ranking. 4 biomarkers were assessed resectability: sCD40L, s100a2, Ca 19-9, CEA.
CONCLUSION
This review has identified and ranked specific biomarkers that should be a primary focus of ongoing validation and clinical translational work in PDAC.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Disease Progression; Disease-Free Survival; Humans; Lymphatic Metastasis; Neoplasm Grading; Neoplasm Recurrence, Local; Pancreatectomy; Pancreatic Neoplasms; Predictive Value of Tests; Risk Factors; Time Factors; Treatment Outcome
PubMed: 27485059
DOI: 10.1016/j.hpb.2016.05.004 -
British Journal of Cancer Mar 2017Radiological markers of treatment response and prognostication in malignant pleural mesothelioma have limitations due to the morphology of the disease. Serum or pleural... (Review)
Review
BACKGROUND
Radiological markers of treatment response and prognostication in malignant pleural mesothelioma have limitations due to the morphology of the disease. Serum or pleural fluid biomarkers that could act as an adjunct to radiological assessment would be of significant value. The aim of this review was to collate and summarise the literature relating to this topic.
METHODS
A systematic review was performed on the databases Pubmed and EMBASE to identify relevant studies. Two independent researchers read the abstracts and used the Quality in Prognostic Studies tool to assess the quality of the evidence.
RESULTS
Forty-five studies were identified from the current literature. Twenty studies investigated the role of serum soluble mesothelin with majority suggesting that it has variable utility as a baseline test but when measured serially correlates with treatment response and prognosis. Several studies demonstrated that serum osteopontin correlated with survival at baseline. Other biomarkers have shown prognostic utility in individual studies but are yet to be reproduced in large cohort studies.
CONCLUSIONS
From the available literature no serum or pleural fluid biomarker was identified that could be recommended currently for routine clinical practice. However, a falling serum soluble mesothelin might correlate with treatment response and improved survival.
Topics: Biomarkers, Tumor; Humans; Mesothelioma; Pleural Neoplasms; Prognosis
PubMed: 28170372
DOI: 10.1038/bjc.2017.22 -
Anais Da Academia Brasileira de Ciencias May 2016The objective of this work was to estimate the accuracy of mesothelin as a biomarker for ovarian cancer. A quantitative systematic review was performed. A comprehensive... (Meta-Analysis)
Meta-Analysis Review
The objective of this work was to estimate the accuracy of mesothelin as a biomarker for ovarian cancer. A quantitative systematic review was performed. A comprehensive search of the Medline, LILACS, SCOPUS, Embase, Cochrane Central Register of Controlled Trials, Biomed Central, and ISI Web of Science databases was conducted from January 1990 to June 2015. For inclusion in this systematic review, the papers must have measured mesothelin levels in at least two histological diagnoses; ovarian cancer (borderline or ovarian tumor) vs. benign or normal ovarian tissue. For each study, 2 x 2 contingency tables were constructed. We calculated the sensitivity, specificity and diagnostic odds ratio. The verification bias was performed according to QUADAS-2. Statistical analysis was performed with the software Stata 11, Meta-DiSc(r) and RevMan 5.2. Twelve studies were analyzed, which included 1,561 women. The pooled sensitivity was 0.62 (CI 95% 0.58 - 0.66) and specificity was 0.94 (CI 95% 0.92 - 0.95). The DOR was 38.92 (CI 95% 17.82 - 84.99). Our systematic review shows that mesothelin cannot serve alone as a biomarker for the detection of ovarian cancer.
Topics: Biomarkers, Tumor; Female; GPI-Linked Proteins; Humans; Mesothelin; Ovarian Neoplasms; Ovary; Sensitivity and Specificity
PubMed: 27254448
DOI: 10.1590/0001-3765201620150107 -
Oncotarget Sep 2016Asbestos is a harmful and exceptionally persistent natural material. Malignant mesothelioma (MM), an asbestos-related disease, is an insidious, lethal cancer that is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Asbestos is a harmful and exceptionally persistent natural material. Malignant mesothelioma (MM), an asbestos-related disease, is an insidious, lethal cancer that is poorly responsive to current treatments. Minimally invasive, specific, and sensitive biomarkers providing early and effective diagnosis in high-risk patients are urgently needed. MicroRNAs (miRNAs, miRs) are endogenous, non-coding, small RNAs with established diagnostic value in cancer and pollution exposure. A systematic review and a qualitative meta-analysis were conducted to identify high-confidence miRNAs that can serve as biomarkers of asbestos exposure and MM.
METHODS
The major biomedical databases were systematically searched for miRNA expression signatures related to asbestos exposure and MM. The qualitative meta-analysis applied a novel vote-counting method that takes into account multiple parameters. The most significant miRNAs thus identified were then subjected to functional and bioinformatic analysis to assess their biomarker potential.
RESULTS
A pool of deregulated circulating and tissue miRNAs with biomarker potential for MM was identified and designated as "mesomiRs" (MM-associated miRNAs). Comparison of data from asbestos-exposed and MM subjects found that the most promising candidates for a multimarker signature were circulating miR-126-3p, miR-103a-3p, and miR-625-3p in combination with mesothelin. The most consistently described tissue miRNAs, miR-16-5p, miR-126-3p, miR-143-3p, miR-145-5p, miR-192-5p, miR-193a-3p, miR-200b-3p, miR-203a-3p, and miR-652-3p, were also found to provide a diagnostic signature and should be further investigated as possible therapeutic targets.
CONCLUSION
The qualitative meta-analysis and functional investigation confirmed the early diagnostic value of two miRNA signatures for MM. Large-scale, standardized validation studies are needed to assess their clinical relevance, so as to move from the workbench to the clinic.
Topics: Asbestos; Biomarkers, Tumor; Computational Biology; Epigenesis, Genetic; GPI-Linked Proteins; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Mesothelin; Mesothelioma; Mesothelioma, Malignant; MicroRNAs; Oligonucleotide Array Sequence Analysis; Phenotype; Tissue Array Analysis; Tissue Distribution
PubMed: 27259231
DOI: 10.18632/oncotarget.9686 -
Asian Pacific Journal of Cancer... 2012Ovarian cancer is the leading cause of death among gynecologic cancers because of the lack of effective early detection methods. Accuracies of the human epididymis... (Review)
Review
BACKGROUND AND PURPOSE
Ovarian cancer is the leading cause of death among gynecologic cancers because of the lack of effective early detection methods. Accuracies of the human epididymis protein 4 (HE4) and mesothelin in detecting ovarian cancer have never been systematically assessed. The current systematic review aimed to tackle this issue.
METHODS
MEDLINE, EMBASE, and Cochrane databases were searched (September 1995-November 2011) for studies on the diagnostic performances of HE4 and mesothelin in differentiating ovarian cancer from other benign gynecologic diseases. QUADAS items were used to evaluate the qualities of the studies. Meta-DiSc software was used to handle data from the included studies and to examine heterogeneity. All included studies for diagnostic performance were combined with sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratios (DORs) with 95% confidence intervals (CIs), summary receiver operating characteristic (SROC) curves, and areas under the SROC curves (AUC).
RESULTS
A total of 18 studies and 3,865 patients were eligible for the final analysis. The pooled sensitivity estimates for HE4 (74.4%) were significantly higher than those for mesothelin (49.3%). The pooled specificity estimates for mesothelin (94.5%) were higher than those for HE4 (85.8%). The pooled DOR estimates for HE4 (26.22) were higher than those for mesothelin (24.01). The SROC curve for HE4 showed better diagnostic accuracy than that for mesothelin. The PLR and NLR of HE4 were 6.33 (95% CI: 3.58 to 11.18) and 0.27 (95% CI: 0.21 to 0.34), respectively. The PLR and NLR for mesothelin were 11.0 (95% CI: 6.21 to 19.59) and 0.51 (95% CI: 0.42 to 0.62), respectively. The combination of the two tumor markers or their combination with CA-125 increased sensitivity and specificity to different extents.
CONCLUSION
The diagnostic accuracy of HE4 in differentiating ovarian cancer from other benign gynecologic diseases is better than that of soluble mesothelin-related protein. Combinations of two or more tumor markers show more sensitivity and specificity.
Topics: Biomarkers, Tumor; Case-Control Studies; Female; GPI-Linked Proteins; Humans; Mesothelin; Meta-Analysis as Topic; Ovarian Neoplasms; Prognosis; Proteins; Software; WAP Four-Disulfide Core Domain Protein 2
PubMed: 23317195
DOI: 10.7314/apjcp.2012.13.11.5427 -
Cancer Cytopathology Feb 2022Cytology effusions are often the only material available for diagnosing malignant pleural mesothelioma (MPM). However, the cytomorphological features alone are not... (Meta-Analysis)
Meta-Analysis Review
Cytology effusions are often the only material available for diagnosing malignant pleural mesothelioma (MPM). However, the cytomorphological features alone are not always diagnostic, and cytology samples preclude an assessment for pleural tissue invasion. Accordingly, immunohistochemical, soluble, and molecular biomarkers have been developed. The aim of this study is to provide quantitative evidence regarding the diagnostic performance of novel biomarkers. To that end, a systematic literature review was performed of articles dealing with a loss of BRCA1-associated protein 1 (BAP1), methylthioadenosine (MTAP), 5-hydroxymethylcitosine (5-hmC), glucose transporter 1 (GLUT1), insulin like-growth factor II messenger RNA-binding protein 3 (IMP3), enhanced zeste homologue 2 (EZH2) staining, cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous deletion (HD) testing, soluble mesothelin, and microRNA quantification in cytological samples for the diagnosis of MPM versus reactive atypical mesothelial cells. Sensitivity and specificity were extracted, and a meta-analysis was performed. The quality of the studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2, and the quality of the evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach. Seventy-one studies were included. BAP1 loss showed a sensitivity of 0.65 (confidence interval [CI], 0.59-0.71) and a specificity of 0.99 (CI, 0.93-1.00). MTAP loss and p16 HD showed 100% specificity with sensitivities of 0.47 (CI, 0.38-0.57) and 0.62 (CI, 0.53-0.71), respectively. BAP1 loss and CDKN2A HD combined showed maximal specificity and a sensitivity of 0.83 (CI, 0.78-0.89). GLUT1 and IMP3 showed sensitivities of 0.82 (CI, 0.70-0.90) and 0.65 (CI, 0.41-0.90), respectively, with comparable specificity. Mesothelin showed a sensitivity of 0.73 (CI, 0.68-0.77) and a specificity of 0.90 (CI, 0.84-0.93). In conclusion, some of the recently emerging biomarkers are close to 1.00 specificity. Their moderate sensitivity on their own, however, can be significantly improved by the use of 2 biomarkers, such as a combination of BAP1 and CDKN2A with fluorescence in situ hybridization or a combination of BAP1 and MTAP immunohistochemistry.
Topics: Biomarkers, Tumor; Glucose Transporter Type 1; Homozygote; Humans; In Situ Hybridization, Fluorescence; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Sequence Deletion
PubMed: 34478240
DOI: 10.1002/cncy.22509 -
European Respiratory Review : An... Dec 2021Malignant pleural mesothelioma (MPM) is characterised by late-stage diagnosis and poor prognosis. Currently, no screening tool is advocated and diagnosis is based on... (Meta-Analysis)
Meta-Analysis Review
Malignant pleural mesothelioma (MPM) is characterised by late-stage diagnosis and poor prognosis. Currently, no screening tool is advocated and diagnosis is based on invasive techniques, which are not well tolerated. Non-invasive diagnostic biomarkers have shown potential and could have a huge clinical benefit. However, despite extensive research, there is no consensus yet on their clinical use, with many articles reporting contradicting results, limiting their clinical implementation. The aim of this systematic review is therefore to explore the different semi- and non-invasive diagnostic markers in several human matrices and identify those that might clinically be relevant. A total of 100 articles were selected through Web of Science and PubMed, with 56 articles included in the quantitative analysis. Although many studies have reported on the diagnostic accuracy of MPM biomarkers such as serum mesothelin and high-mobility group box protein 1 and plasma fibulin-3, none have resulted in a validated test for early detection. Future research should focus on external validation, combinations into biomarker panels, the inclusion of early stage MPM patients and a combination of different biomarker matrices, as well as new markers.
Topics: Biomarkers, Tumor; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Prognosis
PubMed: 34789461
DOI: 10.1183/16000617.0057-2021 -
Diagnostic value of soluble mesothelin-related peptides for malignant mesothelioma: a meta-analysis.Respiratory Medicine Jan 2010Serum concentrations of soluble mesothelin-related peptides (SMRP) have been reported to be higher in patients with malignant mesothelioma than in healthy subjects and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Serum concentrations of soluble mesothelin-related peptides (SMRP) have been reported to be higher in patients with malignant mesothelioma than in healthy subjects and in patients with non-malignant mesothelioma diseases. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of the measurement of SMRPs for diagnosing malignant mesothelioma.
METHODS
After a systematic review of English language studies, sensitivity, specificity, and other measures of accuracy of serum SMRPs in the diagnosis of malignant mesothelioma were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance.
RESULTS
Eleven publications from 12 studies met our inclusion criteria. The summary estimates for SMRPs in the diagnosis of malignant mesothelioma in the studies included were sensitivity 0.64 (95% confidence interval 0.61-0.68), specificity 0.89 (0.88-0.90), positive likelihood ratio 7.10 (4.44-11.35), negative likelihood ratio 0.39 (0.31-0.48), and diagnostic odds ratio 19.35 (10.95-34.17).
CONCLUSIONS
Serum SMRP determination plays a role in the diagnosis of malignant mesothelioma. The results of SMRP assays should be interpreted in parallel with clinical findings and the results of conventional tests.
Topics: Biomarkers, Tumor; GPI-Linked Proteins; Humans; Membrane Glycoproteins; Mesothelin; Mesothelioma; Pleural Neoplasms; Prognosis
PubMed: 19945835
DOI: 10.1016/j.rmed.2009.05.017