The usefulness of biomarkers in diagnosis of asbestos-induced malignant pleural mesothelioma

2021 ◽  
pp. 096032712110173
Author(s):  
Zübeyde Tanrıverdi ◽  
Fatih Meteroglu ◽  
Hande Yüce ◽  
Abdurrahman Şenyiğit ◽  
Mümtaz Işcan ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Early Diagnosis ◽  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Diagnostic Value ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
Spearman Correlation ◽  
Non Invasive ◽  
Noninvasive Markers

Introduction: Malignant pleural mesothelioma (MPM) is a malignant tumor that is associated mostly with asbestos exposure. The present study was to evaluates the diagnostic value of neopterin, periostin, YKL-40, Tenascin-C (TNC), and Indolamine 2,3-dioxygenase (IDO) as noninvasive markers of malign pleural mesothelioma. Methods: Included in the study were 30 patients diagnosed with malign pleural mesothelioma, and 25 people as a control group. Biomarker levels were determined using an enzyme immunoassay . A Mann-Whitney U test and Spearman correlation methods were used for the statistical analysis. Results: All evaluated biomarkers were found to be significantly higher in the MPM group than in the control group ( p < 0.05). There was no effect of such variables as gender, age or MPMsubtype on the parameters ( p > 0.05) in the patient group. All biomarkers were positively correlated with each other ( p < 0.001). Conclusions: The current non-invasive biomarkers that can be used in the diagnosis of MPM yielded significant results and can make important contributions to the early diagnosis of MPM.

scholarly journals Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Danijela Strbac ◽  
Katja Goricar ◽  
Vita Dolzan ◽  
Viljem Kovac
Keyword(s):  
Matrix Metalloproteinases ◽  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Statistical Analyses ◽  
Baseline Risk ◽  
Categorical Variables ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
Environment Interaction ◽  
Risk Predictors

Abstract Background Malignant mesothelioma (MM) is a rare disease, linked to asbestos exposure in more than 80% of the cases. Matrix metalloproteinases (MMPs) have been identified as modulators of the tumour microenvironment and carcinogenesis. Polymorphisms of selected MMPs have been studied as potential biomarkers of time to progression (TTP) and overall survival (OS) in MM. The aim of our study was to investigate selected MMP polymorphisms as baseline risk predictors in MM development in combination with other well known risk factors, such as asbestos exposure. Patients and methods The study included 236 patients and 161 healthy blood donors as the control group. Ten different polymorphisms in three MMP genes were genotyped using a fluorescence-based competitive allele-specific assay (KASPar): MMP2 rs243865, rs243849 and rs7201, MMP9 rs17576, rs17577, rs2250889 and rs20544, and MMP14 rs1042703, rs1042704 and rs743257. In statistical analyses continuous variables were described using median and range (25%–75%), while frequencies were used to describe categorical variables. Deviation from the Hardy-Weinberg equilibrium (HWE) was assessed using the standard chi-square test. The additive and dominant genetic models were used in statistical analyses. The association of genetic polymorphism with MM risk were examined by logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Results Carriers of at least one polymorphic MMP2 rs243865 allele tended to have a decreased risk for MM (OR = 0.66, 95% CI = 0.44–1.00; P = 0.050). The association was more pronounced in patients with known asbestos exposure: carriers of at least one polymorphic allele had significantly lower MM risk (OR = 0.55, 95% CI = 0.35–0.86; P = 0.009). None of the other tested polymorphisms showed association with the risk of malignant pleural mesothelioma. Conclusions The MMP2 rs243865 polymorphism may have a protective role in malignant pleural mesothelioma development. This finding is even more evident in patients exposed to asbestos, implying a strong gene-environment interaction.

Novel malignant-mesothelioma-associated antigens (Gene-X and THBS-2) in the diagnosis of malignant pleural mesothelioma (MPM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10585-10585
Author(s):  
Fumihiro Tanaka ◽  
Yoshiki Shigematsu ◽  
Takeshi Hanagiri ◽  
Hidetaka Uramoto ◽  
Tomoko So ◽  
...  
Keyword(s):  
Antibody Titer ◽  
Malignant Pleural Mesothelioma ◽  
Early Stage ◽  
Asbestos Exposure ◽  
Serum Antibody ◽  
Diagnostic Value ◽  
Pleural Mesothelioma ◽  
Roc Curve Analysis ◽  
Antibody Titers ◽  
Serum Antibody Titer

10585 Background: Malignant pleural mesothelioma (MPM) is a highly aggressive malignant tumor of the pleura associated with asbestos exposure, and its diagnosis is usually difficult at early stage. We identified novel mesothelioma-related antigens, Gene-X and thrombospondin-2 (THBS-2), recognized by tumor-infiltrating B cells (Cancer Sci 2009), but the clinical significance in the diagnosis of MPM remains unclear. Methods: A total of 120 patients, who presented with a suspicion of MPM and received pleural biopsy, were reviewed; 97 patients were finally diagnosed with MPM and 27 were with non-malignant diseases (NM). The antibody-titers against Gene-X and THBS-2 in the sera were measured by ELISA method. Results: The serum antibody-titer against THBS-2 was significantly higher in MPM patients than in NM (P<0.01), but there was no difference in the serum antibody-titer against Gene-X (Table). The receiver operating characteristic (ROC) curve analysis showed a significant diagnostic value of serum antibody-titer against THBS-2 with the area-under curve of 0.886 (95% CI, 0.797 - 0.975; P<0.001) in discrimination of MPM from NM diseases; the sensitivity and specificity, when the cut-off value was 0.08, were 72.2% and 95.5%, respectively. Conclusions: The serum antibody-titer against THBS-2 can be a useful non-invasive marker in the diagnosis of MPM. [Table: see text]

scholarly journals Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

2018 ◽  
Vol 52 (2) ◽  
pp. 160-166 ◽  
Author(s):  
Danijela Strbac ◽  
Katja Goricar ◽  
Vita Dolzan ◽  
Viljem Kovac
Keyword(s):  
Matrix Metalloproteinases ◽  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Statistical Analyses ◽  
Baseline Risk ◽  
Categorical Variables ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
Environment Interaction ◽  
Risk Predictors

Abstract Background Malignant mesothelioma (MM) is a rare disease, linked to asbestos exposure in more than 80% of the cases. Matrix metalloproteinases (MMPs) have been identified as modulators of the tumour microenvironment and carcinogenesis. Polymorphisms of selected MMPs have been studied as potential biomarkers of time to progression (TTP) and overall survival (OS) in MM. The aim of our study was to investigate selected MMP polymorphisms as baseline risk predictors in MM development in combination with other well known risk factors, such as asbestos exposure. Patients and methods The study included 236 patients and 161 healthy blood donors as the control group. Ten different polymorphisms in three MMP genes were genotyped using a fluorescence-based competitive allele-specific assay (KASPar): MMP2 rs243865, rs243849 and rs7201, MMP9 rs17576, rs17577, rs2250889 and rs20544, and MMP14 rs1042703, rs1042704 and rs743257. In statistical analyses continuous variables were described using median and range (25%–75%), while frequencies were used to describe categorical variables. Deviation from the Hardy-Weinberg equilibrium (HWE) was assessed using the standard chi-square test. The additive and dominant genetic models were used in statistical analyses. The association of genetic polymorphism with MM risk were examined by logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Results Carriers of at least one polymorphic MMP2 rs243865 allele tended to have a decreased risk for MM (OR = 0.66, 95% CI = 0.44–1.00; P = 0.050). The association was more pronounced in patients with known asbestos exposure: carriers of at least one polymorphic allele had significantly lower MM risk (OR = 0.55, 95% CI = 0.35–0.86; P = 0.009). None of the other tested polymorphisms showed association with the risk of malignant pleural mesothelioma. Conclusions The MMP2 rs243865 polymorphism may have a protective role in malignant pleural mesothelioma development. This finding is even more evident in patients exposed to asbestos, implying a strong gene-environment interaction.

URINARY EXCRETION OF TGF-Β1 AND VEGF IN CHILDREN WITH VESICOURETERAL REFLUX

2020 ◽  
Vol 73 (11) ◽  
pp. 2411-2415
Author(s):  
Natalia I. Makieieva ◽  
Oksana O. Morozova ◽  
Kateryna K. Iarova ◽  
Yulianna S. Pryima ◽  
Viktoriia O. Golovachova ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Early Diagnosis ◽  
Roc Analysis ◽  
Renal Scarring ◽  
Control Group ◽  
Urine Excretion ◽  
Statistical Parameters ◽  
Non Invasive ◽  
Urine Levels ◽  
Tgf Β1

The aim of this study was to investigate the relation between urinary TGF-β1, urinary VEGF and renal scarring resulted from VUR. Materials and methods: This study included 141 patients with VUR and 34 healthy sex and age matched children. The statistical analysis consisted of descriptive statistical parameters, KruskalWallis, Mann-Whitney tests and ROC analysis. Results: The urine levels of TGF-β1 and VEGF were significantly increased in children with VUR, compared to the controls. The levels of TGF-β1 urine excretion in children with renal scarring were higher compared children no renal scarring. The indicators of VEGF urine excretion in children with renal scarring compared to indicators in children no renal scarring, were lower, however exceeded the indicators in children of control group. The area under the ROC curve for TGF-β1 was 109.9, for VEGF was 207.6. Conclusions: The study allowed to substantiate and propose non-invasive methods for early diagnosis of renal scarring in children with VUR.

Comparison between Plasma and Serum Osteopontin Levels: Usefulness in Diagnosis of Epithelial Malignant Pleural Mesothelioma

2010 ◽  
Vol 25 (3) ◽  
pp. 164-170 ◽  
Author(s):  
Alfonso Cristaudo ◽  
Rudy Foddis ◽  
Alessandra Bonotti ◽  
Silvia Simonini ◽  
Agnese Vivaldi ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Healthy Subjects ◽  
Asbestos Exposure ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
Serum Samples ◽  
Temperature Plasma ◽  
Commercial Laboratory ◽  
Different Temperatures

Background A potential role of serum osteopontin (OPN) and serum mesothelin-related peptide (SMRP) in the diagnosis of malignant pleural mesothelioma (MPM) has been recently reported. Although the most important data regarding the role of OPN in MPMs derive from the marker's measurement in serum samples, most commercial laboratory kits for OPN assay are suitable only for measuring plasma levels, as indicated by the manufacturers. Our study aimed to evaluate the influence of preanalytic variables on serum and plasma OPN, to compare serum and plasma OPN in the same population, and to assess whether OPN levels can aid in the diagnostic distinction of patients with MPM versus benign respiratory disease (BRD) and healthy subjects exposed to asbestos. Methods The influence of preanalytic variables such as the length of storage at different temperatures and the number of thawings of samples on serum and plasma OPN measurements were evaluated. We measured OPN in 239 plasma samples from 207 asbestos-exposed subjects including 94 healthy controls and 113 subjects with BRD, and 32 patients with epithelial MPM, employing a commercially available ELISA. Serum OPN was measured in 196 of the same 239 samples from 80 healthy subjects, 92 BRD patients and 24 MPM patients. Results We found that both serum and plasma OPN levels were influenced by storage at –80°C and by the number of thawings, while serum OPN was influenced also by storage at room temperature. Plasma and serum OPN levels were significantly higher (p<0.0001) in patients with epithelial MPM than in the healthy control group and the BRD group. The application of a ROC curve for plasma OPN resulted in an AUC value of 0.780 with a best cutoff of 878.65 ng/mL, with a sensitivity of 68.8% and a specificity of 84.5%. The AUC for sOPN was 0.725 with a best cutoff of 16.06 ng/mL, with a sensitivity of 62.5% and a specificity of 87.3%. Within the control group no significant correlation was observed between age, duration of asbestos exposure, pack-years in current smokers, lung function or imaging parameters and plasma or serum OPN. Conclusions These data suggest that plasm OPN and serum OPN are not influenced by confounding factors such as age, smoking habits and asbestos exposure. Plasma and serum OPN may be useful markers in the diagnosis of epithelial MPM in addition to traditional radiological exams. However, in our opinion plasma OPN is preferable to serum OPN because it is more stable and measurements of OPN in serum are less reliable.

scholarly journals Circulating biomarkers in malignant pleural mesothelioma

2020 ◽  
Vol 1 (6) ◽  
Author(s):  
Giuseppe Viscardi ◽  
Davide Di Natale ◽  
Morena Fasano ◽  
Marta Brambilla ◽  
Riccardo Lobefaro ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Pleural Mesothelioma ◽  
Precision Oncology ◽  
Advanced Stage ◽  
Circulating Biomarkers ◽  
Prediction Of Response ◽  
Non Invasive ◽  
Prognosis And Prediction ◽  
Aggressive Tumor

Malignant pleural mesothelioma (MPM) is an aggressive tumor strictly connected to asbestos exposure. Prognosis is dismal as diagnosis commonly occurs in advanced stage. Radiological screenings have not proven to be effective and also pathological diagnosis may be challenging. In the era of precision oncology, validation of robust non-invasive biomarkers for screening of asbestos-exposed individuals, assessment of prognosis and prediction of response to treatments remains an important unmet clinical need. This review provides an overview on current understanding and possible applications of liquid biopsy in MPM, mostly focused on the utility as diagnostic and prognostic test.

scholarly journals Serum Mesothelin for Diagnosing Malignant Pleural Mesothelioma: An Individual Patient Data Meta-Analysis

2012 ◽  
Vol 30 (13) ◽  
pp. 1541-1549 ◽  
Author(s):  
Kevin Hollevoet ◽  
Johannes B. Reitsma ◽  
Jenette Creaney ◽  
Bogdan D. Grigoriu ◽  
Bruce W. Robinson ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Diagnostic Accuracy ◽  
Malignant Pleural Mesothelioma ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
Histologic Subtype

Purpose Mesothelin is currently considered the best available serum biomarker of malignant pleural mesothelioma. To examine the diagnostic accuracy and use of serum mesothelin in early diagnosis, we performed an individual patient data (IPD) meta-analysis. Methods The literature search identified 16 diagnostic studies of serum mesothelin, measured with the Mesomark enzyme-linked immunosorbent assay. IPD of 4,491 individuals were collected, including several control groups and 1,026 patients with malignant pleural mesothelioma. Mesothelin levels were standardized for between-study differences and age, after which the diagnostic accuracy and the factors affecting it were examined with receiver operating characteristic (ROC) regression analysis. Results At a common diagnostic threshold of 2.00 nmol/L, the sensitivities and specificities of mesothelin in the different studies ranged widely from 19% to 68% and 88% to 100%, respectively. This heterogeneity can be explained by differences in study population, because type of control group, mesothelioma stage, and histologic subtype significantly affected the diagnostic accuracy. The use of mesothelin in early diagnosis was evaluated by differentiating 217 patients with stage I or II epithelioid and biphasic mesothelioma from 1,612 symptomatic or high-risk controls. The resulting area under the ROC curve was 0.77 (95% CI, 0.73 to 0.81). At 95% specificity, mesothelin displayed a sensitivity of 32% (95% CI, 26% to 40%). Conclusion In patients suspected of having mesothelioma, a positive blood test for mesothelin at a high-specificity threshold is a strong incentive to urge further diagnostic steps. However, the poor sensitivity of mesothelin clearly limits its added value to early diagnosis and emphasizes the need for further biomarker research.

scholarly journals Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

2020 ◽  
Vol 21 (15) ◽  
pp. 5432 ◽  
Author(s):  
Stefano Burgio ◽  
Leila Noori ◽  
Antonella Marino Gammazza ◽  
Claudia Campanella ◽  
Mariantonia Logozzi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Early Diagnosis ◽  
Extracellular Vesicles ◽  
Delivery System ◽  
Malignant Pleural Mesothelioma ◽  
Cell Communication ◽  
Cell Types ◽  
Delivery Systems ◽  
Pleural Mesothelioma ◽  
Potential Use

Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of MPM are both unmet clinical needs. This review looks at indirect and direct evidence that EVs may represent both a new tool for allowing an early diagnosis of MPM and a potential new delivery system for more efficient therapeutic strategies. Since MPM is a relatively rare malignant tumor and preclinical MPM models developed to date are very few and not reliable, this review will report data obtained in other tumor types, suggesting the potential use of EVs in mesothelioma patients as well.

scholarly journals Identification of Redox-Sensitive Transcription Factors as Markers of Malignant Pleural Mesothelioma

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1138
Author(s):  
Martina Schiavello ◽  
Elena Gazzano ◽  
Loredana Bergandi ◽  
Francesca Silvagno ◽  
Roberta Libener ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Malignant Pleural Mesothelioma ◽  
Antioxidant Defense ◽  
Asbestos Exposure ◽  
Predictive Biomarkers ◽  
Antioxidant Systems ◽  
Pleural Mesothelioma ◽  
Related Factor ◽  
Aggressive Cancer

Although asbestos has been banned in most countries around the world, malignant pleural mesothelioma (MPM) is a current problem. MPM is an aggressive tumor with a poor prognosis, so it is crucial to identify new markers in the preventive field. Asbestos exposure induces oxidative stress and its carcinogenesis has been linked to a strong oxidative damage, event counteracted by antioxidant systems at the pulmonary level. The present study has been focused on some redox-sensitive transcription factors that regulate cellular antioxidant defense and are overexpressed in many tumors, such as Nrf2 (Nuclear factor erythroid 2-related factor 2), Ref-1 (Redox effector factor 1), and FOXM1 (Forkhead box protein M1). The research was performed in human mesothelial and MPM cells. Our results have clearly demonstrated an overexpression of Nrf2, Ref-1, and FOXM1 in mesothelioma towards mesothelium, and a consequent activation of downstream genes controlled by these factors, which in turn regulates antioxidant defense. This event is mediated by oxidative free radicals produced when mesothelial cells are exposed to asbestos fibers. We observed an increased expression of Nrf2, Ref-1, and FOXM1 towards untreated cells, confirming asbestos as the mediator of oxidative stress evoked at the mesothelium level. These factors can therefore be considered predictive biomarkers of MPM and potential pharmacological targets in the treatment of this aggressive cancer.

Experimental study of the inhibition effect of CXCL12/CXCR4 in malignant pleural mesothelioma

2018 ◽  
Vol 67 (2) ◽  
pp. 338-345 ◽  
Author(s):  
Jianshuang Li ◽  
Tong Li ◽  
Shuo Li ◽  
Lipeng Xie ◽  
Yi-Lin Yang ◽  
...  
Keyword(s):  
Treatment Group ◽  
Malignant Pleural Mesothelioma ◽  
Synergistic Effects ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
Gene Expressions ◽  
Relationship Of ◽  
The Relationship ◽  
Cxcr4 Axis

Previous studies have demonstrated that CXCL12/CXCR4 axis is closely related to tumors such as malignant pleural mesothelioma (MPM). This research was conducted in order to detect whether CXCL12/CXCR4 inhibitors could restrain MPM and have a synergistic effect with chemotherapy, also to investigate the relationship of CXCL12/CXCR4 with other gene expressions in MPM. Forty mice were injected MPM cells and randomly divided into four groups: the PBS (control group), AMD3100 (CXCR4-CXCL12 antagonist), pemetrexed and AMD3100 plus pemetrexed. The mice were treated respectively for duration of 3 weeks. The size, bioluminescence and weight of tumors were measured. The differences between gene expressions in each group were analyzed. The tumor weights of each treatment group were lower than that of the control group (p<0.05). The bioluminescence of the tumor of the AMD3100 treatment group and the AMD3100 plus pemetrexed treatment group were lower than that of the control group (p<0.05), and AMD3100 was shown to have synergistic effects with pemetrexed (p<0.05). Among the 2.5 billion genes, several hundreds of genes expressed differently between groups. Results show that AMD3100 and pemetrexed can inhibit the growth of MPM in vivo, also that there is a better result if both are used together. Our findings suggest that CXCL12/CXCR4 axis affects a certain amount of gene expression in MPM.

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