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1.
Transl Lung Cancer Res ; 13(6): 1420-1425, 2024 Jun 30.
Article de Anglais | MEDLINE | ID: mdl-38973944

RÉSUMÉ

Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with high morbidity and mortality. A combination of systemic therapy and surgery may be a promising modality for the treatment of MPM, but evidence-based medicine is still lacking. Case Description: Here we report a case of MPM. The patient presented to hospital with cough and sputum. After ineffective symptomatic treatment, computed tomography (CT) examination suggested a malignant tumor of pleural origin. Positron emission tomography/computed tomography (PET/CT) examination suggested no lymph node metastasis or distant metastasis. The pathologic diagnosis of MPM was confirmed after CT-guided puncture biopsy. Next, she underwent 3 courses of neoadjuvant chemotherapy combined with dual immunotherapy (carboplatin and pemetrexed combined with anti-CTLA4 and anti-PD-1), resulting in significant tumor shrinkage. After obtaining the patient's consent and completing a preoperative evaluation, we modified the extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) by performing a lower lobe resection and partial pleurectomy of the left lung. Intraoperative rapid frozen pathology suggested that the margins of the tumor were negative and complete resection was achieved. The postoperative pathology report showed 10% residual viable tumor, so the major pathological response (MPR) was achieved after treatment. Conclusions: MPM might respond well to neoadjuvant chemotherapy and dual immunotherapy, improving the probability of complete surgical resection and attaining an encouraging pathologic response.

2.
Article de Chinois | MEDLINE | ID: mdl-38538248

RÉSUMÉ

The occurrence of malignant mesothelioma is related to exposure of asbestos. And many researchers have conducted in-depth analysis of the molecular changes of mesothelioma, showed that its molecular characteristics were chromosome changes, including chromosome rearrangement, gene mutation and gene deletion. Recent studies have strengthened our understanding of molecular characterization of mesothelioma, such as targeted mutations of tumor suppressor genes, differential gene expression, changes of miRNA and signal pathways. It is of great significance for the early diagnosis, clinical treatment and prognosis of malignant mesothelioma to explore the pathogenesis and development of malignant mesothelioma. This article reviews the research progress on the pathogenesis and carcinogenesis-related molecules of malignant mesothelioma.


Sujet(s)
Amiante , Tumeurs du poumon , Mésothéliome malin , Mésothéliome , Tumeurs de la plèvre , Humains , Mésothéliome malin/complications , Tumeurs du poumon/génétique , Tumeurs du poumon/anatomopathologie , Tumeurs de la plèvre/génétique , Mésothéliome/génétique , Mésothéliome/diagnostic
3.
J Thorac Dis ; 16(1): 671-687, 2024 Jan 30.
Article de Anglais | MEDLINE | ID: mdl-38410609

RÉSUMÉ

Background and Objective: Malignant pleural mesothelioma (MPM) is a very aggressive primary tumor of the pleura whose main risk factor is exposure to asbestos. However, only a minority of exposed people develops MPM and the incidence of MPM cases without an apparent association with asbestos exposure has been increasing in recent years, suggesting that genetic predisposing factors may play a crucial role. In addition, several studies reported familial cases of MPM, suggesting that heredity may be an important and underestimated feature in MPM development. Several candidate genes have been associated with a predisposition to MPM and most of them play a role in DNA repair mechanisms: overall, approximately 20% of MPM cases may be related to genetic predisposition. A particular category of patients with high susceptibility to MPM is represented by carriers of pathogenic variants in the BAP1 gene. Germline variants in BAP1 predispose to the development of MPM following an autosomal dominant pattern of inheritance in the familial cases. MPMs in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. In the present narrative review, we presented a comprehensive overview of genetic susceptibility in the development of MPM. Methods: The narrative review is based on a selective literature carried out in PubMed in 2023. Inclusion criteria were original articles in English language, and clinical trials (randomized, prospective, or retrospective). Key Content and Findings: We summarized the somatic and germline variants and the differences in terms of clinicopathological features and prognosis between gene-related MPM (GR-MPM) and asbestos-related MPM (AR-MPM). We also discussed the indications for screening, genetic testing, and surveillance of patients with BAP1 germline variants. Conclusions: In this narrative review, we have emphasized that the BAP1 gene's harmful germline variations are inherited in an autosomal dominant manner in familial cases. MPMs in individuals with these variations are less severe, and their medical care necessitates a collaborative effort. Additionally, we have outlined the current therapeutic prospects for MPM, including the possibility of gene-specific therapy, which is currently promising but still requires clinical validation.

4.
Lung Cancer ; 187: 107440, 2024 01.
Article de Anglais | MEDLINE | ID: mdl-38104353

RÉSUMÉ

OBJECTIVES: Nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA-4) is a new first-line treatment combination for patients with pleural mesothelioma. Nivolumab-ipilimumab improved the survival, however, 30.3% of the patients suffered from grade 3-4 treatment related adverse events (TRAE's) and TRAE's led to discontinuation in 23.0% of all patients. Here, we present the first real-world data of nivolumab plus ipilimumab in patients with malignant mesothelioma treated in two mesothelioma expert centers. METHODS: Clinical data of patients with mesothelioma treated with nivolumab and ipilimumab were prospectively collected. Clinical parameters were obtained every visit, CT scans were evaluated every 12 weeks and adverse events were assessed continuously during the treatment. Data on grade 2-5 TRAE's and activity (overall response rate (ORR), duration of response (DOR), disease control rate (DCR), median progression-free survival (mPFS) and median overall survival (mOS) were reported. RESULTS: Between January 2021 and August 2022, 184 patients were treated with nivolumab plus ipilimumab. The median follow-up was 12.1 months (95 %CI 11.1 - 13.1). Grade 3-4 TRAEs were seen in 27.7 % of the patients and 25.0 % discontinued immunotherapy treatment early because of TRAE's. ORR was 21.7 % (95 % CI 15.7-27.7), median DOR was 5.7 months (IQR 3.2-8.7) and DCR at 12 weeks 56.0 % (95 % CI 48.8-63.2). The mPFS was 5.5 months (95 %CI 4.1-6.9), mOS was 14.1 months (95 % CI 11.1-18.2). CONCLUSIONS: Nivolumab plus ipilimumab had an equal efficacy in a real-world comparable population but also a high risk of TRAE's, leading to discontinuation of treatment in 25% of the patients.


Sujet(s)
Tumeurs du poumon , Mésothéliome malin , Mésothéliome , Humains , Nivolumab/effets indésirables , Ipilimumab/effets indésirables , Mésothéliome malin/traitement médicamenteux , Tumeurs du poumon/anatomopathologie , Mésothéliome/anatomopathologie , Protocoles de polychimiothérapie antinéoplasique/effets indésirables
5.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 41(11): 869-875, 2023 Nov 20.
Article de Chinois | MEDLINE | ID: mdl-38073220

RÉSUMÉ

Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, characterized by insidious onset, strong local invasiveness, short survival period, and poor prognosis. Clinical diagnosis is of paramount importance for the treatment and prognosis of MPM. Currently, the gold standard for diagnosing MPM is the results of histopathological examinations. Immunohistochemistry (IHC) is an effective auxiliary method in pathological diagnosis. Preliminary examinations can use two positive markers and two negative markers to distinguish pleural metastatic tumors, with additional antibodies selected based on differential diagnosis. The combined use of IHC markers plays a crucial role in the differential diagnosis between MPM and other tumors. This article primarily introduces commonly used IHC markers in MPM and the research progress of novel IHC markers in screening and differential diagnosis, aiming to provide reference for the clinical diagnosis and treatment of MPM.


Sujet(s)
Tumeurs du poumon , Mésothéliome malin , Mésothéliome , Tumeurs de la plèvre , Humains , Mésothéliome malin/anatomopathologie , Mésothéliome/diagnostic , Tumeurs du poumon/diagnostic , Tumeurs du poumon/anatomopathologie , Tumeurs de la plèvre/diagnostic , Plèvre/anatomopathologie , Marqueurs biologiques tumoraux
6.
Transl Cancer Res ; 12(10): 2887-2897, 2023 Oct 31.
Article de Anglais | MEDLINE | ID: mdl-37969363

RÉSUMÉ

Background: Malignant pleural mesothelioma (MPM) is a rare disease with limited treatment and poor prognosis, and a precise and reliable means to predicting MPM remains lacking for clinical use. Methods: In the population-based cohort study, we collected clinical characteristics from the Surveillance, Epidemiology, and End Results (SEER) database. According to the time of diagnosis, the SEER data were divided into 2 cohorts: the training cohort (from 2010 to 2016) and the test cohort (from 2017 to 2019). The training cohort was used to train a deep learning-based predictive model derived from DeepSurv theory, which was validated by both the training and the test cohorts. All clinical characteristics were included and analyzed using Cox proportional risk regression or Kaplan-Meier curve to determine the risk factors and protective factors of MPM. Results: The survival model included 3,130 cases (2,208 in the training cohort and 922 in the test cohort). As for model's performance, the area under the receiver operating characteristics curve (AUC) was 0.7037 [95% confidence interval (CI): 0.7030-0.7045] in the training cohort and 0.7076 (95% CI: 0.7067-0.7086) in the test cohort. Older age; male sex, sarcomatoid mesothelioma; and T4, N2, and M1 stage tended to be the risk factors for survival. Meanwhile, epithelioid mesothelioma, surgery, radiotherapy, and chemotherapy tended to be the protective factors. The median overall survival (OS) of patients who underwent surgery combined with radiotherapy was the longest, followed by those who underwent a combination of surgery, radiotherapy, and chemotherapy. Conclusions: Our deep learning-based model precisely could predict the survival of patients with MPM; moreover, multimode combination therapy might provide more meaningful survival benefits.

7.
Article de Chinois | MEDLINE | ID: mdl-37805421

RÉSUMÉ

Objective: To explore and analyze differential expressed genes in malignant pleural mesothelioma (MPM) by bioinformatics method, and to study their prognostic value in MPM and their potential role in immunotherapy. Methods: In January 2022, the dataset GSE51024 was downloaded from the GEO database, and MPM (55 cases) and normal tissue (41 cases) samples were obtained. Using R software and HMDD and miRNet database, MPM-related differential genes were screened and co-expressed genes were identified. Co-expressed genes were enriched and functionally annotated, and protein-protein interaction (PPI) networks were constructed and key genes were identified using the STRING database and Cytoscape software. TRRUST and GEPIA databases were used to predict transcription factors of key genes and to analyze prognosis and survival. The correlation between key genes and the degree of infiltration of immune cells was analyzed using TIMER. Results: A total of 435 co-expressed genes were obtained, which were mainly concentrated in the extracellular matrix tissue and the signaling pathways of cell adhesion molecules. Combined with PPI and TRRUST database, seven key MPM prognostic genes were identified. Among them, cyclin 20 (CDC20) , cell cycle checkpoint kinase 1 (CHEK1) , enhancer of Zeste homolog 2 (EZH2) , ribonucleotide reductase subunit M2 (RRM2) , topoisomerase 2A (TOP2A) , ubiquitin like plant homeodomain and ring finger domain 1 (UHRF1) were significantly up-regulated in MPM, while cyclin A1 (CCNA1) was significantly down-regulated. The expressions of CCNA1, CDC20, CHEK1, EZH2, RRM2, TOP2A and UHRF1 genes were significantly associated with MPM overall survival (P<0.05) . The expressions of CDC20, CHEK1, EZH2, RRM2 and TOP2A genes were positively correlated with B cells and dendritic cells (P<0.05) , and negatively correlated with neutrophils (P<0.05) . Conclusion: CCNA1, CDC20, CHEK1, EZH2, RRM2, TOP2A and UHRF1 may be potential prognostic markers in MPM patients, and their expressions may be related to MPM tumor immunity.


Sujet(s)
Tumeurs du poumon , Mésothéliome malin , Mésothéliome , Tumeurs de la plèvre , Humains , Pronostic , Transduction du signal , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Tumeurs du poumon/génétique , Protéines liant les séquences stimulatrices de type CCAAT/métabolisme , Ubiquitin-protein ligases
8.
Cureus ; 15(8): e43744, 2023 Aug.
Article de Anglais | MEDLINE | ID: mdl-37727202

RÉSUMÉ

Malignant mesothelioma is a very rare diagnosis. Malignant mesotheliomas arise from surface linings of pleura, peritoneal cavity, or tunica vaginalis and pericardium with pleural malignant mesotheliomas being the most common. The incidence of brain metastases has been very low with malignant pleural mesotheliomas, but to date, there have not been any cases reported of brain metastasis with malignant peritoneal mesotheliomas. We present a patient diagnosed with malignant peritoneal mesothelioma and was successfully treated with immunotherapy for over two years but later presented with brain metastases. Although the patient had a surgical resection followed by brain radiation, he died three months after his diagnosis of brain metastases. Immunotherapy has revolutionized the treatment of malignant mesothelioma, and patients are living longer than before. We present this patient to increase awareness of brain metastases with malignant peritoneal mesothelioma. This case also highlights that we need to investigate different treatment options for brain metastases in patients with malignant mesothelioma as conventional treatment options like surgical resection and brain radiation are not very effective.

9.
Transl Cancer Res ; 12(8): 1929-1936, 2023 Aug 31.
Article de Anglais | MEDLINE | ID: mdl-37701096

RÉSUMÉ

Background: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal prognosis. Currently, multimodality treatment including chemotherapy with cisplatin or carboplatin in combination with pemetrexed offers the best options. Detoxification of heavy metals in the cell by metallothioneins (MT) is associated with early failure to platin-based chemotherapy. The induction of MTs gene expression or its enzyme results in saturation by exposure to metal ions such as zinc or cadmium. Its therapeutically effect is still not analyzed in depth. Methods: In our study, we investigated three MPM cell lines and one fibroblast cell line in the course of cisplatin treatment and supplementation of zinc. Cell state analyses via an enzyme-activity based assay were performed. With this, we were able to analyze apoptosis, necrosis and viability of cells. Additionally, we tested treated cells for changes in metallothionein IIA (MT2A) expression by using quantitative realtime polymerase chain reaction. Results: Zinc supplementation induces gene expression of MT2A. Overall, a zinc dose-dependent induction of apoptosis under platin-based treatment could be observed. This effect could be verified in all analyzed cell lines in varying intensity. Conclusions: MT expression is induced by zinc in a dose-dependent manner and inhibits a successful cisplatin therapy. Therefore, heavy metal exposure during cisplatin therapy, e.g., via cigarette smoke, might be an important factor. This should be considered in further therapeutic approaches.

10.
Transl Lung Cancer Res ; 12(7): 1384-1390, 2023 Jul 31.
Article de Anglais | MEDLINE | ID: mdl-37577311

RÉSUMÉ

Background: Malignant pleural mesothelioma (MPM) is an incurable, late presenting primary cancer, conferring a survival of 8-14 months. Different intrapleural treatments have been tested as part of a multimodality approach to treat a select group of patients with limited disease, increasing survival. Recently, povidone-iodine has been shown to induce apoptosis in microscopic tumour cells in vitro, with no reported complications. This is the first in vivo study assessing the apoptotic rate caused by intraoperative hyperthermic betadine lavage using routine immunohistochemistry combined with transmission electron microscopy (TEM). Methods: We included surgically fit patients aged >18, undergoing minimally invasive video-assisted thoracoscopic surgery (VATS) pleural biopsy between December 2016 and February 2018, for confirmed or presumed pleural malignancy. Parietal pleural biopsies were obtained at 7.5, 15 and 30 minutes after hyperthermic betadine lavage, and compared to pre-lavage biopsy samples, for apoptotic changes. Viable tumour samples underwent histological, immunohistochemical and ultrastructural analysis as well as TEM for features of apoptosis. Results: N=6. Median age was 76 years. Median overall survival was 26.7 months. There was no statistical impact on survival of side of disease (left vs. right). There was no significant difference in expressions of markers of apoptotic index pre and post betadine treatment upon immunohistochemical analysis. There was no discernible effect on morphological features of apoptosis seen with betadine treatment, on TEM analysis. No side effects were identified post betadine lavage. Conclusions: Although hyperthermic betadine lavage is a safe antiseptic solution with no toxicity when performed intraoperatively, it confers no effect on apoptotic rate or necrosis. It is therefore unlikely that hyperthermic betadine lavage will have an impact on reducing the microscopic residual disease after pleurectomy decortication and enhancing survival.

11.
Cureus ; 15(3): e36479, 2023 Mar.
Article de Anglais | MEDLINE | ID: mdl-37090283

RÉSUMÉ

Malignant pleural mesothelioma (MPM) involves the uncontrolled growth of mesothelial cells that form the lining of pleural serous layers. MPM has been linked with asbestos exposure in mining and manufacturing occupations with an unforgiving prognosis of 4-18 months. In this case report, we present a 56-year-old male with a significant past medical history of hypertension, hyperlipidemia, hepatic steatosis, and ulcerative colitis who presented to the emergency department for worsening cough, eight-pound weight loss over the previous year, night sweats, and fatigue. The patient was admitted due to right pleural effusion with lower lobe collapse seen on imaging; upon diagnostic workup including pleural biopsy, results were consistent with malignant mesothelioma of the epithelioid type. Over the course of six months post-diagnosis, the patient underwent multiple hospital admissions due to acute hypoxic respiratory failure from the segmental left upper lobe and subsegmental right upper lobe pulmonary emboli, recurrent pleural effusion, and anemia. Given the aggressive nature of MPM, the patient was determined not to be a surgical candidate and underwent palliative chemotherapy sessions until his passing. As the patient worked in heating/ventilation/air conditioning with asbestos exposure, taking a full occupational history was crucial. MPM is relatively rare; however, the incidence has increased over the last decade due to tumor development lag time post-asbestos exposure and an increase in do-it-yourself projects. There is no cure for MPM. Multimodal treatment approaches with surgery, chemotherapy, radiotherapy, and immunotherapy have been noted in the literature.

14.
Cureus ; 15(1): e33965, 2023 Jan.
Article de Anglais | MEDLINE | ID: mdl-36687288

RÉSUMÉ

Mesothelioma is a rare and insidious neoplasm and is characterized by its highly malignant and aggressive nature. The most common etiology is asbestos exposure, but there are some reports without known asbestos exposure and other factors leading to malignant pleural mesothelioma (MPM). Here, we present the case of a 58-year-old woman with pleuritic chest pain, dyspnea, and fever on presentation to the emergency department (ED), which caused several admissions to the ED in 20 days. The patient was then admitted to the internal medicine department with a diagnosis of community-acquired pneumonia with parapneumonic effusion. During hospitalization, a positron emission tomography (PET) scan, thoracic computed tomography (CT), and pleural biopsy were performed and a final diagnosis of malignant epithelioid pleural mesothelioma was made. Six weeks after the onset of symptoms, the patient presented with an exponential disease progression, dying two months after the diagnosis, despite the initiation of chemotherapy. MPM remains a diagnostic and therapeutic challenge with a very poor prognosis. However, studies show that mesothelioma patients who undergo treatment live at least twice as long as patients who do not receive treatment. This case report is particularly significant because, although it was epithelioid mesothelioma, multiple solid masses were noted on CT and the patient exhibited rapid disease progression, dying a few weeks after starting treatment.

15.
Cancer Immunol Immunother ; 72(4): 865-879, 2023 Apr.
Article de Anglais | MEDLINE | ID: mdl-36115921

RÉSUMÉ

Programmed cell death protein-1 (PD1), PD1 ligand 1 (PD-L1), and human leukocyte antigen (HLA) class I molecule play pivotal roles in T cell-induced anti-tumor immunity; however, the clinical impact of these parameters in resected malignant pleural mesothelioma (MPM) cases is unknown. We immunohistochemically evaluated the tumor infiltrated lymphocytes (TILs), PD1/PD-L1 axis, and expression of HLA class I in resected specimens from 58 patients with MPM who underwent extra-pleural pneumonectomy (EPP). Higher infiltration of CD3-TIL, CD8-TIL, and PD1-TIL, loss of HLA class I, and overexpression of PD-L1 by tumor cells (PD-L1 TC) or immune cells (PD-L1 IC) were observed in 34 (58.6%), 27 (46.6%), 41 (70.7%), 45 (77.6%), 29 (50.0%), and 33 (56.4%) of 58 cases, respectively. Interestingly, the CD3-TIL score positively correlated with PD-L1 TC and PD1-TIL scores. HLA class I expression level was inversely correlated with the expression levels of PD-L1 TC and PD-L1 IC. Multivariate analysis showed that age, histology, and node metastasis were independent prognostic factors for 5-year overall survival (OS) and loss of HLA class I coincided with a positive prognosis (p = 0.011). The concomitant lack of infiltrating CD8+ T cells with no loss of HLA class I predicted worse 5-year OS (p = 0.007). Moreover, cluster classifications among multiple immunoparameters showed that categories among CD3/PD-L1 TC/HLA class I (p = 0.043), CD8/PD1/HLA class I (p = 0.032), CD8/PD-L1 TC/HLA class I (p = 0.011), and PD1/PD-L1 TC/HLA class I (p = 0.032) predicted 5-year OS in EPP cases for MPM. These immunoparameters could guide surgical indications for patients with MPM.


Sujet(s)
Mésothéliome malin , Humains , Mésothéliome malin/anatomopathologie , Antigène CD274/métabolisme , Pneumonectomie , Ligands , Lymphocytes TIL , Pronostic , Lymphocytes T CD8+ , Antigènes d'histocompatibilité de classe I
16.
Article de Anglais | MEDLINE | ID: mdl-36152987

RÉSUMÉ

OBJECTIVE: In the event of suspicion of malignant pleural mesothelioma (MPM) progression, imaging plays an important role. We aimed to evaluate the efficacy of 18F-FDG PET/CT in monitoring disease progression by comparing it with CT, and estimate median overall survival (OS) according to progression status with CT and 18F-FDG PET/CT. MATERIALS AND METHODS: This was an observational, retrospective, single-institution study with MPM patients who had both 18F-FDG PET/CT and CT for monitoring disease progression from March 2009 to February 2020. Clinical features, radiological findings, and progression status according to CT [radiologic progression negative (RPN), radiologic progression positive (RPP)] and 18F-FDG PET/CT [metabolic progression negative (MPN), metabolic progression positive (MPP)] were recorded. The discrepancies and concordance between two methods were evaluated. The OS was estimated using the Kaplan-Meier method. RESULTS: A total of 56 patients were included. There were thirty-one (55.3%) RPN and 25 (44.7%) RPP, while there were 26 (46.5%) MPN and 30 (53.5%) MPP. All RPP patients were also found to be MPP, however, among RPN, 5 patients (8.9% of all patients) were evaluated as MPP. The concordance between two methods in monitoring disease progression was very good (K = 0.423; p < 0.01). The OS was 26 ±â€¯2.6 months in all patients. Kaplan-Meier curves between RPN and RPP, and between MPN and MPP did not show statistically significant differences (p = 0.56 and p = 0.25, respectively). CONCLUSIONS: Both methods are equally acceptable in monitoring disease progression in MPM, even though 18F-FDG PET/CT detected more progression than CT did.


Sujet(s)
Tumeurs du poumon , Mésothéliome malin , Mésothéliome , Humains , Mésothéliome malin/imagerie diagnostique , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Fluorodésoxyglucose F18 , Mésothéliome/imagerie diagnostique , Mésothéliome/anatomopathologie , Études rétrospectives , Tumeurs du poumon/anatomopathologie , Évolution de la maladie
17.
Front Endocrinol (Lausanne) ; 13: 1056152, 2022.
Article de Anglais | MEDLINE | ID: mdl-36523602

RÉSUMÉ

Background: Glycolysis-related genes as prognostic markers in malignant pleural mesothelioma (MPM) is still unclear. We hope to explore the relationship between glycolytic pathway genes and MPM prognosis by constructing prognostic risk models through bioinformatics and machine learning. Methods: The authors screened the dataset GSE51024 from the GEO database for Gene set enrichment analysis (GSEA), and performed differentially expressed genes (DEGs) of glycolytic pathway gene sets. Then, Cox regression analysis was used to identify prognosis-associated glycolytic genes and establish a risk model. Further, the validity of the risk model was evaluated using the dataset GSE67487 in GEO database, and finally, a specimen classification model was constructed by support vector machine (SVM) and random forest (RF) to further screen prognostic genes. Results: By DEGs, five glycolysis-related pathway gene sets (17 glycolytic genes) were identified to be highly expressed in MPM tumor tissues. Also 11 genes associated with MPM prognosis were identified in TCGA-MPM patients, and 6 (COL5A1, ALDH2, KIF20A, ADH1B, SDC1, VCAN) of them were included by Multi-factor COX analysis to construct a prognostic risk model for MPM patients, with Area under the ROC curve (AUC) was 0.830. Further, dataset GSE67487 also confirmed the validity of the risk model, with a significant difference in overall survival (OS) between the low-risk and high-risk groups (P < 0.05). The final machine learning screened the five prognostic genes with the highest risk of MPM, in order of importance, were ALDH2, KIF20A, COL5A1, ADH1B and SDC1. Conclusions: A risk model based on six glycolytic genes (ALDH2, KIF20A, COL5A1, ADH1B, SDC1, VCAN) can effectively predict the prognosis of MPM patients.


Sujet(s)
Glycolyse , Apprentissage machine , Mésothéliome malin , Mésothéliome , Humains , Aldehyde dehydrogenase, mitochondrial/métabolisme , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Biologie informatique/méthodes , Glycolyse/génétique , Mésothéliome/diagnostic , Mésothéliome/génétique , Mésothéliome malin/diagnostic , Mésothéliome malin/génétique , Pronostic
18.
J Pers Med ; 12(12)2022 Dec 02.
Article de Anglais | MEDLINE | ID: mdl-36556214

RÉSUMÉ

Malignant pleural mesothelioma (MPM) is a highly lethal malignancy that unfortunately cannot benefit from molecularly targeted therapies. Although previous results showed the pivotal role of various receptor tyrosine kinases (RTKs) in MPM tumorigenesis, the treatment with a single inhibitor targeting one specific RTK has been shown to be ineffective in MPM patients. The main aim of the present study was to investigate the potential role of AXL and MET receptors in MPM and the possible efficacy of treatment with AXL and MET multitarget inhibitors. Immunohistochemical and FISH analyses were performed in a wide series of formalin-fixed paraffin-embedded MPM samples to detect the expression of two receptors and the potential gene amplification. In vitro studies were performed to evaluate putative correlations between the target's expression and the cell sensitivity to AXL-MET multitarget inhibitors. In our series, 10.4% of cases showed a co-expression of AXL and MET, regardless of their ligand expression, and the gene amplification. Furthermore, our in vitro results suggest that the concomitant pharmacological inhibition of AXL and MET may affect the proliferative and aggressiveness of MPM cells. In conclusion, the subset of MPM patients with AXL-MET co-activation could benefit from treatment with specific multitarget inhibitors.

19.
Cureus ; 14(10): e30345, 2022 Oct.
Article de Anglais | MEDLINE | ID: mdl-36407243

RÉSUMÉ

Malignant pleural mesothelioma (MPM) typically has a short median survival of only a few months from diagnosis, with death usually due to thoracic disease. This has led to the belief in the past that mesothelioma rarely has distant metastasis, with cerebral metastasis accounting for only 3%. The multiple cases of brain metastasis from MPM recorded so far were discovered after death at autopsy. This report describes a rare case of known malignant mesothelioma with distant haemorrhagic metastasis to the brain, reviews current literature about its metastatic potential to the brain and discusses prognosis and management. We also review the imaging evaluation in known MPM patients with suspected intracranial involvement and describe typical imaging findings of parenchymal brain metastasis on computed tomography (CT) and magnetic resonance imaging (MRI).

20.
Front Oncol ; 12: 1027149, 2022.
Article de Anglais | MEDLINE | ID: mdl-36276110

RÉSUMÉ

Background: Malignant pleural mesothelioma (MPM) is an uncommon condition with limited available therapies and dismal prognoses. The purpose of this work was to create a multivariate clinical prognostic nomogram and a web-based survival risk calculator to forecast patients' prognoses. Methods: Using a randomization process, training and validation groups were created for a retrospective cohort study that examined the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 for individuals diagnosed with MPM (7:3 ratio). Overall survival (OS) and cancer-specific survival (CSS) were the primary endpoints. Clinical traits linked to OS and CSS were identified using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis, which was also utilized to develop nomogram survival models and online survival risk calculators. By charting the receiver operating characteristic (ROC), consistency index (C-index), calibration curve, and decision curve analysis (DCA), the model's performance was assessed. The nomogram was used to classify patients into various risk categories, and the Kaplan-Meier method was used to examine each risk group's survival rate. Results: The prognostic model comprised a total of 1978 patients. For the total group, the median OS and CSS were 10 (9.4-10.5) and 11 (9.4-12.6) months, respectively. As independent factors for OS and CSS, age, gender, insurance, histology, T stage, M stage, surgery, and chemotherapy were chosen. The calibration graphs demonstrated good concordance. In the training and validation groups, the C-indices for OS and CSS were 0.729, 0.717, 0.711, and 0.721, respectively. Our nomogram produced a greater clinical net benefit than the AJCC 7th edition, according to DCA and ROC analysis. According to the cut-off values of 171 for OS and 189 for CSS of the total scores from our nomogram, patients were classified into two risk groups. The P-value < 0.001 on the Kaplan-Meier plot revealed a significant difference in survival between the two patient groups. Conclusions: Patient survival in MPM was correctly predicted by the risk evaluation model. This will support clinicians in the practice of individualized medicine.

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