Multiplexed genetic analysis of malignant pleural mesothelioma and the relationship to clinical outcome.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7582-7582
Author(s):  
Takehito Shukuya ◽  
Masakuni Serizawa ◽  
Masato Abe ◽  
Hiroaki Akamatsu ◽  
Takaaki Tokito ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Malignant Pleural Mesothelioma ◽  
Gene Mutations ◽  
Pleural Mesothelioma ◽  
Pik3ca Amplification ◽  
Fresh Frozen ◽  
The Relationship ◽  
Genotyping Panel ◽  
Tumor Genotyping ◽  
Gene Alterations

7582 Background: Genotype-based stratification is essential to improve cancer treatment. We have developed a multiplexed tumor genotyping panel for detecting gene alterations relevant to molecular targeted therapies. We applied this genotyping panel to malignant pleural mesothelioma (MPM) and evaluate the relationship between clinical outcome and gene alterations. Methods: Surgical specimens and tumor biopsies from 40 patients with MPM were collected from 2003 to 2012. Pathological diagnoses were confirmed by immunohistochemistry in addition to HE stain. 37 patients were genotyped with multiplexed tumor genotyping panel developed to assess 9 gene mutations (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN and HER2) and 5 genes amplifications (EGFR, MET, PIK3CA, FGFR1 and FGFR2) using pyrosequencing plus capillary electrophoresis, and qRT-PCR, respectively. Other 3 patients were analyzed by ultra-deep targeted sequencing with next generation sequencer. 5 fusion genes (EML4-ALK, CD74-ROS1, SLC34A2-ROS1, KIF5B-RET and CCDC6-RET) were tested in 2 patients with fresh frozen specimens. Results: Gene alterations were detected in 6 patients (Table shown below). These patients harboring gene alterations showed poorer survival than the patients in whom gene alterations were not detected (median survival time (MST): 583 vs 164 days, log-lank: p=0.009). Moreover, the patients with PIK3CA amplification/mutation showed poorer survival than the patients without PIK3CA amplification/mutation (MST: 583 vs 103 days, log-lank: p=0.031). Conclusions: Gene alterations which could be a target for molecular targeted therapy were detected in MPM. Especially, PIK3CA pathway is a potential target. [Table: see text]

scholarly journals Radical Hemithoracic Radiotherapy Induces Systemic Metabolomics Changes That Are Associated with the Clinical Outcome of Malignant Pleural Mesothelioma Patients

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 508
Author(s):  
Emanuela Di Gregorio ◽  
Gianmaria Miolo ◽  
Asia Saorin ◽  
Elena Muraro ◽  
Michela Cangemi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Overall Survival ◽  
Clinical Outcome ◽  
Malignant Pleural Mesothelioma ◽  
Therapeutic Option ◽  
Enrichment Analysis ◽  
Metabolic Effects ◽  
Pleural Mesothelioma ◽  
Polyamine Biosynthesis ◽  
The Individual

Radical hemithoracic radiotherapy (RHRT) represents an advanced therapeutic option able to improve overall survival of malignant pleural mesothelioma patients. This study aims to investigate the systemic effects of this radiotherapy modality on the serum metabolome and their potential implications in determining the individual clinical outcome. Nineteen patients undergoing RHRT at the dose of 50 Gy in 25 fractions were enrolled. Serum targeted metabolomics profiles were investigated at baseline and the end of radiotherapy by liquid chromatography and tandem mass spectrometry. Univariate and multivariate OPLS-DA analyses were applied to study the serum metabolomics changes induced by RHRT while PLS regression analysis to evaluate the association between such changes and overall survival. RHRT was found to affect almost all investigated metabolites classes, in particular, the amino acids citrulline and taurine, the C14, C18:1 and C18:2 acyl-carnitines as well as the unsaturated long chain phosphatidylcholines PC ae 42:5, PC ae 44:5 and PC ae 44:6 were significantly decreased. The enrichment analysis showed arginine metabolism and the polyamine biosynthesis as the most perturbed pathways. Moreover, specific metabolic changes encompassing the amino acids and acyl-carnitines resulted in association with the clinical outcome accounting for about 60% of the interpatients overall survival variability. This study highlighted that RHRT can induce profound systemic metabolic effects some of which may have a significant prognostic value. The integration of metabolomics in the clinical assessment of the malignant pleural mesothelioma could be useful to better identify the patients who can achieve the best benefit from the RHRT treatment.

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.

scholarly journals P3.03-042 Study Comparing Volume and TNM in Predicting Clinical Outcome in Malignant Pleural Mesothelioma

2017 ◽  
Vol 12 (1) ◽  
pp. S1371
Author(s):  
Claudia Proto ◽  
Diego Signorelli ◽  
Sandra Mallone ◽  
Francesca Greco ◽  
Giuseppina Calareso ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma

scholarly journals Downregulation of miR-99a/let-7c/miR-125b miRNA cluster predicts clinical outcome in patients with unresected malignant pleural mesothelioma

Oncotarget ◽  
2017 ◽  
Vol 8 (40) ◽  
pp. 68627-68640 ◽  
Author(s):  
Anna Truini ◽  
Simona Coco ◽  
Ernest Nadal ◽  
Carlo Genova ◽  
Marco Mora ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Mirna Cluster

scholarly journals DNA Methylation of FKBP5 as Predictor of Overall Survival in Malignant Pleural Mesothelioma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3470
Author(s):  
Giovanni Cugliari ◽  
Chiara Catalano ◽  
Simonetta Guarrera ◽  
Alessandra Allione ◽  
Elisabetta Casalone ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
P Value ◽  
Pleural Mesothelioma ◽  
Lymphocyte To Monocyte Ratio ◽  
High Incidence ◽  
Aggressive Tumor ◽  
Independent Marker ◽  
The Relationship

Malignant pleural mesothelioma (MPM) is an aggressive tumor with median survival of 12 months and limited effective treatments. The scope of this study was to study the relationship between blood DNA methylation (DNAm) and overall survival (OS) aiming at a noninvasive prognostic test. We investigated a cohort of 159 incident asbestos exposed MPM cases enrolled in an Italian area with high incidence of mesothelioma. Considering 12 months as a cut-off for OS, epigenome-wide association study (EWAS) revealed statistically significant (p value = 7.7 × 10−9) OS-related differential methylation of a single-CpG (cg03546163), located in the 5′UTR region of the FKBP5 gene. This is an independent marker of prognosis in MPM patients with a better performance than traditional inflammation-based scores such as lymphocyte-to-monocyte ratio (LMR). Cases with DNAm < 0.45 at the cg03546163 had significantly poor survival compared with those showing DNAm ≥ 0.45 (mean: 243 versus 534 days; p value< 0.001). Epigenetic changes at the FKBP5 gene were robustly associated with OS in MPM cases. Our results showed that blood DNA methylation levels could be promising and dynamic prognostic biomarkers in MPM.

Clinical and Pathologic Predictors of Clinical Outcome of Malignant Pleural Mesothelioma

2016 ◽  
Vol 102 (2) ◽  
pp. 190-195 ◽  
Author(s):  
Rossana Berardi ◽  
Ilaria Fiordoliva ◽  
Mariagrazia De Lisa ◽  
Zelmira Ballatore ◽  
Miriam Caramanti ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma

scholarly journals CD157 enhances malignant pleural mesothelioma aggressiveness and predicts poor clinical outcome

Oncotarget ◽  
2014 ◽  
Vol 5 (15) ◽  
pp. 6191-6205 ◽  
Author(s):  
Erika Ortolan ◽  
Alice Giacomino ◽  
Francesca Martinetto ◽  
Simona Morone ◽  
Nicola Lo Buono ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Poor Clinical Outcome

scholarly journals Non-occupational malignant pleural mesothelioma due to asbestos and non-asbestos fibres

2016 ◽  
Vol 65 (4) ◽  
Author(s):  
L. Proietti ◽  
L. Spicuzza ◽  
A. Di Maria ◽  
R. Polosa ◽  
E. Sebastian Torres ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Genetic Factors ◽  
Epidemiologic Studies ◽  
Pleural Mesothelioma ◽  
Environmental Carcinogens ◽  
Case Control Studies ◽  
Epidemiological Evidence ◽  
Electronic Search ◽  
Professional Exposure ◽  
The Relationship

Background and aim. The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). Methods. An electronic search of literature related to non occupational MPM was performed including the year 2005. Results. Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. Conclusion. It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos- like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.

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