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PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive cancer with long latency and poor prognosis. The real-world treatment patterns and humanistic burden of MPM in an international cohort of patients were recently published. Spanish data are currently lacking and are reported here. METHODS/PATIENTS: Data were collected from three sources: physician-abstracted demographic, clinical and treatment characteristics of patients with MPM; patient-completed questionnaires on treatment satisfaction, symptoms, caregiver use, and impact of the disease; and caregiver-completed questionnaire reporting their activity and its impact on their daily life. RESULTS: The 241 patients in Spain were primarily elderly (median age: 67 years), male, retired/unemployed/on long-term sick leave, and diagnosed at stage IV with unresectable disease. Exposure to asbestos was detected (54%, 101/188). First-line treatment (1L) consisted primarily of doublet chemotherapy (86%, 207/241). Of 102 patients who completed 1L at data abstraction, 67 were receiving maintenance therapy, most commonly singlet chemotherapy with pemetrexed. Best supportive care was given to 29 patients, primarily after 1L (86.2%, 25/29). Symptom burden was high and health-related quality of life was poor and declined with progression: mean (SD) EQ-5D score and EQ-5D visual analogue scale score were 0.615 (0.285) and 60.8 (17.1) in 1L and 0.497 (0.370) and 56.1 (19.5) in second line. Overall, 67% of patients (162/241) required daily assistance from their caregiver, who reported an impact on their psychological well-being. CONCLUSIONS: Patients with MPM in Spain were overall treated according to treatment guidelines at the time. Nevertheless, a considerable burden of disease was reported by patients and caregivers.
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Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural tissue that lines the lungs and is mainly associated with long latency from asbestos exposure. This tumor has no effective therapeutic opportunities nowadays and has a very low five-year survival rate. In this sense, identifying molecular events that trigger the development and progression of this tumor is highly important to establish new and potentially effective treatments. We conducted a meta-analysis of genome-wide expression studies publicly available at the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were identified, and we performed functional enrichment analysis and protein-protein interaction networks (PPINs) to gain insight into the biological mechanisms underlying these genes. Additionally, we constructed survival prediction models for selected DEGs and predicted the minimum drug inhibition concentration of anticancer drugs for MPM. In total, 115 MPM tumor transcriptomes and 26 pleural tissue controls were analyzed. We identified 1046 upregulated DEGs in the MPM samples. Cellular signaling categories in tumor samples were associated with the TNF, PI3K-Akt, and AMPK pathways. The inflammatory response, regulation of cell migration, and regulation of angiogenesis were overrepresented biological processes. Expression of SOX17 and TACC1 were associated with reduced survival rates. This meta-analysis identified a list of DEGs in MPM tumors, cancer-related signaling pathways, and biological processes that were overrepresented in MPM samples. Some therapeutic targets to treat MPM are suggested, and the prognostic potential of key genes is shown.
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Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Mesotelioma/genética , Mesotelioma/metabolismo , Fosfatidilinositol 3-Quinases , Neoplasias Pleurais/genética , Neoplasias Pleurais/metabolismo , Neoplasias Pulmonares/patologiaRESUMO
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor, with a poor prognosis. MPM needs to find prognostic factors of survival. We provided the management of patients with MPM and sought to determine whether pre-treatment levels of derived neutrophil-to-lymphocyte ratio (dNLR) as well as PD-L1 expression were reliable prognostic factors of survival. METHODS: We conducted a single-institution retrospective study, including all patients with MPM treated at La Paz University Hospital between December 2009 and March 2018. Baseline disease, demographics, clinical data, treatment characteristics and complete blood cell counts were collected. We examined dNLR at baseline and data for PD-L1 expression were analyzed in tumor cells by immunohistochemistry. RESULTS: We included 25 patients. The median overall survival (OS) was 15.7 months (95% CI 11.3-20.0). 5 patients had a dNLR greater than 3 (20%). Patients with a dNLR greater than 3 had shorter median OS (8.5 months), than patients with a dNLR less than 3 (17.0 months), with statistically significant differences (p = 0.038). Ten patients (40%) had positive PD-L1 expression (≥ 1%). Patients with positive PD-L1 expression had shorter median OS (8.5 months) than patients with negative PDL1 expression (15.7 months), but without statistically significant association (p = 0.319). CONCLUSION: The survival data obtained in our sample are consistent with those previously reported. Pretreatment levels of dNLR greater than 3 and positive PD-L1 expression could be significant prognostic factors for poor survival in patients with MPM. Further and prospective studies are needed to explore this relationship and to derive definitive conclusions.
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Antígeno B7-H1/metabolismo , Linfócitos/citologia , Mesotelioma Maligno/sangue , Neutrófilos/citologia , Neoplasias Pleurais/sangue , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Contagem de Células Sanguíneas , Feminino , Humanos , Imuno-Histoquímica , Masculino , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma Maligno/mortalidade , Mesotelioma Maligno/patologia , Pessoa de Meia-Idade , Pemetrexede/uso terapêutico , Compostos de Platina/uso terapêutico , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/patologia , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: Malignant pleural mesothelioma is an infrequent neoplasia with a poor prognosis and the majority of patients already have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Mesothelioma is a neoplasia with a long preclinical stage that can span from 15 to 40 years. METHODS: This was a descriptive, observational, retrospective study of 136 patients with a confirmed diagnosis of mesothelioma, which compared histological subtypes, immunohistochemical biomarkers, concomitant chronic degenerative diseases, tobacco use, age at the time of diagnosis, clinical stage and chemotherapy agents used or other treatments such as radiotherapy and surgery to identify all the factors that impact in the prognosis of overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 136 patients were included in the study. In the total study population, 84 patients were male (61.8%) and 52 were female (38.2%). Median PFS was nine months (95% confidence interval [CI]: 8.4-9.5 months) and median OS was 12 months (95% CI: 11.3-12.6). The results indicated that the most determining prognostic factors for OS and PFS were cell differentiation measured by immunohistochemical biomarkers, the treatment chosen, and that RECIST was the most significant in the evaluation of patient response to treatment. CONCLUSIONS: Malignant pleural mesothelioma is a cancer with a poor prognosis usually diagnosed at an advanced stage of disease. Our study revealed that the prognostic factors for OS and PS were cell differentiation, the treatment chosen and RECIST.
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Mesotelioma Maligno/mortalidade , Adolescente , Adulto , Feminino , Humanos , Masculino , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Adulto JovemRESUMO
Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.
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Mesotelioma Maligno/diagnóstico , Mesotelioma Maligno/terapia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapia , Antineoplásicos/uso terapêutico , Amianto/toxicidade , Carcinógenos/toxicidade , Terapia Combinada/métodos , Procedimentos Cirúrgicos de Citorredução , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoterapia/métodos , Oncologia , Mesotelioma Maligno/etiologia , Mesotelioma Maligno/patologia , Estadiamento de Neoplasias , Pemetrexede/uso terapêutico , Compostos de Platina/uso terapêutico , Neoplasias Pleurais/etiologia , Neoplasias Pleurais/patologia , Radioterapia/métodos , Sociedades Médicas , Espanha , Vinorelbina/uso terapêutico , GencitabinaRESUMO
RESUMEN Introducción: El mesotelioma pleural maligno es un tumor maligno primario de la pleura, comúnmente asociado con la exposición al asbesto. Se considera una patología rara y muy agresiva. Objetivo: Realizar una revisión sobre los criterios de diagnóstico y tratamiento actualizados en torno al mesotelioma pleural maligno. Métodos: Se realizó una revisión bibliográfica en fuentes de información disponibles en la Biblioteca Virtual de Salud, de la red telemática Infomed, entre ellas, las bases de datos SciELO, Pubmed/Medline, Cumed, Lilacs, así como el Google Académico. Se seleccionaron un total de 39 referencias. Conclusiones: Existen pocas referencias en la literatura nacional relacionadas con el diagnóstico, tratamiento y seguimiento de los pacientes con mesotelioma pleural maligno. El diagnóstico combina el uso del método clínico, los estudio imagenológicos e histoquímicos. No existe un tratamiento estándar, siendo recomendable un enfoque individualizado que combine según cada caso, cirugía, quimio y radioterapia. Los desafíos futuros incluyen el desarrollo de nuevas alternativas terapéuticas(AU)
ABSTRACT Introduction: Malignant Pleural Mesothelioma is a primary malignant tumor of the pleura, commonly associated with exposure to asbestos. It is considered a rare and very aggressive pathology. Objective: Conduct a review of updated diagnostic and treatment criteria for malignant pleural mesothelioma. Material and Methods: A bibliographic review was made through the search of information in sources available from the Cuban National Health Care Network and Portal (INFOMED), among them, databases such as SciELO, Pubmed / Medline, Cumed, Lilacs, as well as Google Scholar. Finally, a total of 39 references were selected for our study. Conclusions: There are few references in the national literature related to the diagnosis, treatment and follow-up of patients with malignant pleural mesothelioma. The diagnosis combines the use of the clinical method, the imaging and histochemical studies. There is no standard treatment, being recommended an individualized approach that combines according to each case, surgery, chemo and radiotherapy. Future challenges include the development of new therapeutic alternatives(AU)
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Humanos , Amianto/efeitos adversos , Literatura de Revisão como Assunto , Mesotelioma/diagnóstico , Mesotelioma/terapia , Bases de Dados Bibliográficas , Fibras MineraisRESUMO
INTRODUCTION: The asbestos industry began operations in Colombia in 1942, with an asbestos-cement facility located in the municipality of Sibaté. In recent years residents from Sibaté have been complaining about what they consider is an unusually large number of people diagnosed with asbestos-related diseases in the town. A study to analyze the situation of Sibaté started in 2015, to verify if the number of asbestos related diseases being diagnosed were higher than expected, and to identify potential asbestos exposure sources in the town. METHODS: A health and socioeconomic survey was implemented door-to-door to identify potential asbestos-related diseases. Several self-reported mesothelioma cases were identified, and for confirmation purposes, copies of the medical record with the histopathology report were obtained. A panel of six physicians analyzed the medical records. Information of validated cases was used to estimate the male and female age-adjusted incidence rate for Sibaté. Based on reports of the existence of potential asbestos-contaminated landfills, topographic maps, a digital elevation model, and current satellite images were crossed using a geographic information system to identify potential landfilled areas, and soils samples were collected in some of these areas. RESULTS: A total of 355 surveys were completed, and 29 self-reported mesothelioma cases were identified. Twenty-five of these cases have been persons who had lived at some moment of their lives in Sibaté. It was possible to obtain copies of the medical diagnosis for 17 cases. Of these, the panel of physicians classified 15 cases as certain pleural mesothelioma, one as probable, and one as not mesothelioma. Based on this information, the estimated age-adjusted incidence rate of mesothelioma in Sibaté was 3.1â¯×â¯105 persons-year for males and 1.6â¯×â¯105 persons-year for females. These rates are high in comparison to those reported in other cities, regions, and countries of the world. Using geographic information systems, landfilled zones in the urban area of Sibaté were identified, on top of which a school and different sports facilities were built. The analysis of four soil samples collected in landfilled zones, confirmed the existence of an underground layer of friable and non-friable asbestos. CONCLUSION: The collected evidence suggests the presence of a malignant pleural mesothelioma cluster in Sibaté.
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Amianto , Mesotelioma , Exposição Ocupacional , Adulto , Amianto/toxicidade , Cidades , Colômbia , Exposição Ambiental , Feminino , Humanos , Incidência , Masculino , Mesotelioma/epidemiologia , Pessoa de Meia-IdadeRESUMO
RESUMEN Se presenta un paciente exfumador de 65 años que, un año antes de comenzar las manifestaciones respiratorias, comenzó con dolores óseos erráticos, tratados con medicamentos comunes hasta que es atendido por disnea, tos y dolor torácico en el Hospital Básico San Antonio, ciudad de Riobamba, provincia de Chimborazo, Ecuador. El paciente presenta un gran derrame pleural, del cual obtienen 1500 ml de líquido serohemático, cuyo estudio citológico es positivo de malignidad. Se somete a cirugía, se confirma histológicamente mesotelioma maligno en etapa IV y se trata posteriormente con quimioterapia, pero el paciente empeora progresivamente hasta fallecer. Los autores resaltan que las manifestaciones paraneoplásicas del cáncer del pulmón son más frecuentes cuando la localización es parenquimatosa y no pleural, y llaman la atención sobre el hecho de que en este paciente comenzaron 1 año antes de que aparecieran los síntomas respiratorios.
ABSTRACT We present a 65-year-old ex-smoker patient, in which respiratory manifestations with erratic bone pain treated with common medications, began a year before he was atended for dyspnea, cough and chest pain at "San Antonio" Basic Hospital, Riobamba city, Chimborazo province, Ecuador. The patient presented a large pleural effusion of 1500 ml of serohematic fluid. Cytological study was positive for malignancy to rule out mesothelioma. Surgery was performed, histologically malignant mesothelioma was confirmed in stage IV and treated with chemotherapy. But the patient worsens progressively until death. Authors emphasized that lung cancer paraneoplastic manifestations were more frequent in not pleural and parenchymal location. They also called attention to patients´ symptoms, which began one year before the respiratory condition appeared.
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Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with 67Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.
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Anticorpos Monoclonais Humanizados/farmacocinética , Radioisótopos de Gálio/farmacocinética , Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Neoplasias Pleurais/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Linhagem Celular Tumoral , Fluordesoxiglucose F18/química , Humanos , Imageamento Tridimensional , Fígado/metabolismo , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Mesotelioma/diagnóstico por imagem , Mesotelioma Maligno , Camundongos Nus , Neoplasias Pleurais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor that originates in the pleura, is diagnosed in advanced stages and has a poor prognosis. Accurate diagnosis of MPM is often difficult and complex, and the gold standard diagnosis test is based on qualitative analysis of markers in pleural tissue by immunohistochemical staining. Therefore, it is necessary to develop quantitative and non-subjective alternative diagnostic tools. MicroRNAs are non-coding RNAs that regulate essential cellular mechanisms at the post-transcriptional level. Recent evidence indicates that miRNA expression in tissue and body fluids is aberrant in various tumors, revealing miRNAs as promising diagnostic biomarkers. This review summarizes evidence regarding secreted and tissue miRNAs as biomarkers of MPM and the biological characteristics associated with their potential diagnostic value. In addition to studies regarding miRNAs with potential diagnostic value for MPM, studies that aimed to identify the miRNAs involved in molecular mechanisms associated with MPM development are described with an emphasis on relevant aspects of the experimental designs that may influence the accuracy, consistency and real diagnostic value of currently reported data.
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Biomarcadores Tumorais/genética , Neoplasias Pulmonares/genética , Mesotelioma/genética , MicroRNAs/genética , Neoplasias Pleurais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Mesotelioma/diagnóstico , Mesotelioma/patologia , Mesotelioma Maligno , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/patologia , Distribuição TecidualRESUMO
Se actualizan aspectos etiopatogénicos, clínicos, diagnósticos y terapéuticos en el mesotelioma pleural maligno, enfermedad temida e infrecuente en nuestro medio. Nos impresionó sobremanera, una profesional de salud tratada recientemente y en etapa temprana que apenas sobrevivió un año. El objetivo es elevar el conocimiento sobre el tema para tratar de mejorar la sobrevida. Se presentan una síntesis de ocho pacientes estudiados y tratados con este diagnóstico en los hospitales "Amalia Simoni", "Manuel Ascunce Domenech", "Madam Curie" de Camagüey y el "Martín Chang Puga" de Nuevitas desde 1998 hasta 2015, señalando el cuadro clínico, exámenes complementarios, diagnóstico, tratamiento médico quirúrgico y los resultados. Más de la mitad de los pacientes eran fumadores con pequeño derrame pleural inicial que hicieron pensar en la enfermedad, todo lo contrario cuando no existió derrame. Hubo tres enfermos donde el diagnóstico nos sorprendió por lo inesperado. La sobrevida fue baja con una media alrededor de 11 meses, solo uno vivió dos años. Los complementarios utilizados se ajustan a otros reportes y nuestras posibilidades. El tratamiento fue actualizado y acorde a otras series en el momento del diagnóstico. Se compara nuestra casuística, la cual se asemeja a publicaciones foráneas en cuanto a diagnóstico, tratamiento y sobrevida. Señalamos que, independiente de algunos recursos desde el punto de vista diagnóstico y terapéutico con que no contamos, los resultados se ajustan a la literatura actual y la sobrevida lograda fue sin dudas, adversa(AU)
Several etiopathogenetic, clinical, diagnostic and therapeutic aspects of the malignant pleural mesothelioma, fearful and infrequent disease in our context, are updated. It was really impressive the case of a female health professional that was recently treated at early stage of disease and barely survived one year. The objective of this review was to raise the level of knowledge on this disease in oder to improve survival rates. To this end, eight patients with this diagnosis, who were studied and treated in "Amalia Simoni", "Manuel Ascunce Domenech", "Madame Curie" hospitals in Camaguey and in "Martin Chang Puga" in Nuevitas from 1998 to 2015 were presented. Their clinical picture, supplementary tests, diagnosis, medical and surgical treatment and final results were described. Half of them were smokers with initial small pleural effusion that made the specialists suspect the existence of the disease. There were three patients whose diagnoses surprised the physicians because they were unexpected. Survival was low and the average survival rate was 11 months, although one managed to live two years. The indicated supplementary tests were similar to those of other reports and adjusted to our setting. Treatment was updated and consistent with other series at the time of diagnosis. The casuistry in our conditions was compared to others and it was similar in terms of diagnosis, treatment and survival rates to the one shown in foreign publication. Regardless of some unavailable diagnostic and therapeutic resources, the results of the treatment agree with those of the current literature on the topic and the survival rate was undoubtedly negative(AU)
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Mesotelioma/complicações , Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/mortalidade , Radiografia Abdominal/estatística & dados numéricosRESUMO
Pleural chronic inflammation (PP) and mesothelial hyperplasia (HP) may be critical to the development of malignant pleural mesothelioma (MPM). Nonetheless, studies searching for mechanistic links involving microRNA (miRNA) regulation among these interrelated processes have not been reported. Using PCR-Array, we identified the miRNAs expressed in pleural tissues diagnosed with MPM (n=5), PP (n=4) and HP (n=5), as well as in non-cancerous/non-inflammatory tissue as the normal control (n=5). We performed bioinformatics and network analysis of differentially expressed miRNAs to identify tumorigenesis-related miRNAs and their biological networks. The targets of four down-regulated miRNAs in MPM (mir-181a-5p, miR-101-3p, miR-145-5p and miR-212-3p), one in PP (mir-101-3p) and one in HP (mir-494) were significantly enriched in "pathways in cancer". Interactome networks revealed that >50% of down-regulated miRNAs in MPM targeted the signaling-activation molecule MAPK1, the transcription factor ETS1 and the mesenchymal transition-associated molecule FZDA, which have been associated with oncogenic function. Comparative analysis revealed that FZD4 was an overlapping gene target of down-regulated miRNAs that were associated with "pathways in cancer" in MPM, PP and HP. Moreover, MAPK1, ETS1 and Cox-2, a pro-inflammatory enzyme associated with over-expression in cancers, were among the 25 overlapping target genes in MPM and PP. This network analysis revealed a potential combinatory effect of deregulated miRNAs in MPM pathogenesis and indicated potential molecular links between pleural inflammation and hyperplasia with tumorigenesis mechanisms in pleura.
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Carcinogênese/genética , Neoplasias Pulmonares/genética , Mesotelioma/genética , MicroRNAs/análise , Neoplasias Pleurais/genética , Lesões Pré-Cancerosas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperplasia/genética , Hiperplasia/patologia , Inflamação/genética , Inflamação/patologia , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/patologia , Mesotelioma Maligno , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia , Transcriptoma , Adulto JovemRESUMO
Accurate diagnosis of malignant pleura mesothelioma (MPM) is challenging. Differential diagnosis of MPM versus lung adenocarcinoma (AD) is particularly difficult, yet clinically important since the two neoplasias call for different treatment approaches. Circulating miRNA-profiling to identify miRNAs that can be used to distinguish MPM from AD has not been reported. We conducted a wide screening study of miRNA profiles in serum pools of MPM patients (N = 11), AD patients (N = 36), and healthy subjects (N = 45) to identify non-invasive biomarkers for differential diagnosis of MPM and AD, using deep sequencing. Sequencing detected up to 300 known miRNAs and up to 25 novel miRNAs species in the serum samples. Among known miRNAs, 7 were upregulated in MPM and 12 were upregulated in AD compared to healthy controls. Of these, eight were distinctive for AD and three were unique for MPM. Direct comparison of the miRNA profiles for MPM and AD revealed differences in miRNA levels that could be useful for differential diagnosis. No differentially expressed novel miRNAs were found. Further bioinformatics analysis indicated that three upregulated miRNAs in MPM are associated with the p38 pathway. There are unique alterations in serum miRNAs in MPM and AD compared to healthy controls, as well as differences between MPM and AD profiles. Differing miRNA levels between MPM and AD may be useful for differential diagnosis. A potential association to p38 pathway of three upregulated miRNAs in MPM was revealed.
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Introduction: Malignant Pleural Mesothelioma (MPM) is a tumor of the mesothelial cells related to asbestos exposure. This malignancy is extremely aggressive, with poor response to different treatment modalities, and it has a mean survival of 8 months since diagnosis. With the introduction of new chemotherapeutic agents and trimodality protocols, five-year survival of 40 percent in initial stages has been reported. Serum detection of Soluble Mesothelin-related Protein (SMRP) could be used for screening of MPM. Using the MESOMARK® test, 53 percent of MPM patients had levels greater than 1,5 nM, while 99 percent of control patients had lower concentrations. The aim of this study is to evaluate the use of this test in Chile and determine its utility for screening ofMPM. Methods: Quantitative blind measurement of serum SMRP by MESOMARK® test. We studied 3 groups: 8 workers exposed to asbestos, 5 patients with diagnosed MPM and 14 age matched workers without known exposure to asbestos. Participants were informed of the study. Results: Mean +/- standard deviation SMRP levels in the control group was 0,53 +/- 0,4 nM, 0,89 +/- 0,46 nM in patients exposed to asbestos and 10,68 +/- 10,28 nM in MPMpatients. Differences between the groups were statistically significant (p = 0,02). In the MPM group, 3 patients were found to have SMRP levels greater than 1,5 nM (17,27 nM; SD 6,95) and 2 patients normal values (0,79 nM; SD 0,32). Using a cut-off value of 1,5 nM, sensitivity of the test was 60 percent and specificity was 100 percent. Conclusions: Detection of SMRP levels allowed to identify patients with MPM, three of whom had very high concentrations. The sensitivity and specificity found is similar to that previously reported. If our results are confirmed in greater studies, SMRP detection could be used for screening of MPM.
Resumen Introducción: El Mesotelioma Maligno (MM) es un tumor de las células mesoteliales relacionado a la exposición a asbesto, altamente agresivo, con pobre respuesta al tratamiento y con una sobrevida promedio de 8 meses después del diagnóstico. Sin embargo, nuevos agentes quimioterapéuticos y protocolos de terapia trimodal han logrado sobrevidas de hasta 40 por ciento en etapas iniciales. La detección en sangre periférica de Péptidos Solubles Relacionados a Mesotelina (SMRP) podría ser útil para el diagnóstico precoz de MM. Utilizando el test MESOMARK® para la determinación de SMRP, 53 por ciento de los pacientes con MM tenían valores mayores a 1,5 nM mientras que 99 por ciento de los controles mostraron valores inferiores. El objetivo del presente trabajo es evaluar la implementación de este test en Chile y determinar su utilidad para el diagnóstico precoz en MM. Métodos: Medición cuantitativa de SMRP en suero humano por test MESOMARK®. Se realizaron mediciones en forma ciega a 8 trabajadores con exposición a asbesto, a 5 pacientes con MMy a 14 voluntarios sin exposición. Todos los participantes fueron informados del estudio. Resultados: El promedio +/- desviación estándar de SMRP en el grupo control fue de 0,53 +/- 0,4 nM, de 0,89 +/- 0,46 nM en los expuestos sin MMy de 10,68 +/- 10,28 nM en el grupo con MM; encontrándose una diferencia estadísticamente significativa entre los valores de estos tres grupos (p = 0,02). En el grupo con MM, 3 pacientes tuvieron concentraciones mucho mayores a 1,5 nM (17,27 nM; DS 6,95) y 2 valores normales (0,79 nM; DS 0,32). Utilizando un valor de 1,5 nM como punto de corte, la sensibilidad fue de 60 por ciento y la especificidad de 100 por ciento. Conclusiones: La medición de SMRP permitió diferenciar a los pacientes con MM, presentando 3 de ellos concentraciones muy elevadas. La sensibilidad y especificidad encontrada es similar con datos previamente reportados. De confirmarse estos resultados en estudios con mayor ...