Study of the metabolomic relationship between lung cancer and chronic obstructive pulmonary disease based on direct infusion mass spectrometry.

The high prevalence of lung cancer (LC) has triggered the search of biomarkers for early diagnosis of this disease. For this purpose the study of metabolic changes related to the development of lung cancer could provide interesting information about its early diagnosis. In this sense, chronic obstructive pulmonary disease (COPD), a disease associated with tumor development, is a comorbidity that increases the risk of onset and progression of lung neoplasia and has also to be considered in the study of pathology related to lung cancer. This work develop a metabolomic approach based on direct infusion mass spectrometry using a hybrid triple quadrupole-time of flight mass spectrometer (DI-ESI-QqQ-TOF-MS) in order to identify altered metabolites from serum of LC and COPD patients and evaluate its relationship and implication in the progression of LC. This methodology has been applied to 30 serum samples from LC, 30 healthy patients used as controls (HC) and 30 serum samples from COPD to found altered metabolites from both LC and COPD diseases. In addition, some metabolic differences and similarities were found in Pulmonary Emphysema and Chronic Bronchitis patients. On the other hand, altered metabolites were studied in different stages of LC (II, III and IV) to evaluate the perturbation of them throughout the progression of disease. The sample treatment consisted of the extraction of polar and non-polar metabolites from serum that was later infused into the mass spectrometer using an electrospray ionization source in positive and negative mode. Partial least squares discriminant analysis (PLS-DA) allowed a classification between LC, HC and COPD groups in all acquisition modes. A total of 35 altered and common metabolites between LC and COPD, including amino acids, fatty acids, lysophospholipids, phospholipids and triacylglycerides were identified, being alanine, aspartate and glutamate metabolism the most altered. Finally, ROC curves were applied to the dataset and metabolites with AUC value higher than 0.70 were considered as relevant in the progression of LC.

Algoritmo de retirada de corticoides inhalados en la EPOC / No disponible

No disponible

Perfiles metabolómicos de sujetos sanos y con cáncer de pulmón. Influencia de la carga tabáquica / The metabolomics of healthy subjects and those with lung cancer: the influence of smoking

INTRODUCCIÓN: la aplicación de técnicas metabolómicas presenta un gran potencial para la búsqueda de posibles biomarcadores de diagnóstico precoz en numerosas enfermedades. El empleo de procedimientos metabolómicos basados en espectrometría de masas permite estudiar las modificaciones metabólicas subyacentes al cáncer de pulmón (CP) y la influencia de la carga tabáquica (CT), medida en paquetes-año, en los correspondientes perfiles metabólicos. METODOLOGÍA: se estudió el suero de 9 controles sanos (no fumadores), 6 enfermos de CP con carga tabáquica moderada (CT 70). Se analizaron los metabolitos mediante técnicas de espectrometría de masas de alta resolución (DI-ESI-QTOFMS). Los perfiles metabólicos obtenidos se sometieron a análisis estadístico multivariante (PCA, PLS-DA). RESULTADOS: los tres grupos de estudio mostraron perfiles metabólicos claramente diferentes, lo que permitió identificar algunos posibles biomarcadores. Los niveles de glutatión se encontraron disminuidos en muestras de suero de pacientes con CP, mientras que se incrementó el contenido de distintos fosfolípidos de membrana (PL). La mayoría de estas anormalidades metabólicas se acentuó en pacientes con una CT elevada. CONCLUSIONES: el análisis metabolómico en muestras de suero permitió diferenciar claramente entre sujetos sanos y pacientes con CP. Así mismo, se identificaron posibles biomarcadores para el diagnóstico del CP (relacionados con rutas previamente conocidas en el proceso del cáncer). Además, estas alteraciones se vieron influenciadas por la carga tabáquica, confirmando la importancia del tabaquismo como factor de riesgo primario en el desarrollo del CP

By using high resolution metabolomics, we obtained the metabolomic profiles for patients who smoked and had lung cancer (LC) and a healthy, non-smoker control (HC) group; we assessed the influence of smoking on said profiles. The results show a clear discrimination between the metabolomic profiles of both groups studied; the metabolites causing said difference could be determined. Moreover, differences were encountered between the metabolomic profiles of heavy smokers with lung cancer compared to moderate smokers. INTRODUCTION: theapplicationof metabolomic techniques offers extensive potential to search for possible biomarkers in the early detection of several diseases. Using metabolomic procedures based on mass spectrometry allow us to study underlying metabolic changes in lung cancer and the influence of smoking, measured as packets/year, in the corresponding metabolic profiles. METHOD: the serum from 9 healthy control subjects (nonsmokers) was studied, as well as that of 6 patients with lung cancer who were moderate smokers (CT 70). The metabolites were analyzed using high resolution mass spectrometer techniques (DI-ESI-QTOF-MS). The metabolic profiles obtained were subject to multivariate statistical analysis (PCA, PLS-DA). RESULTS: the three groups studied showed clearly differentiated metabolic profiles, which facilitated the identification of certain biomarkers. Glutathione levels were found to be decreased in the sample from patients with lung cancer, while the content of various membrane phospholipids increased. Most of these metabolic abnormalities were heightened in patients who were heavy smokers. CONCLUSIONS: the metabolomics analysis in serum samples clearly differentiated healthy subjects from patients with lung cancer. Also, possible biomarkers were identified to diagnose lung cancer (linked to previously known routes in the cancer process. Moreover, these alterations were influenced by the amount smoked, thus confirming the importance of smoking as a primary risk factor in developing lung cáncer

Sarcoma intimal de arteria pulmonar: causa infrecuente de hipertensión pulmonar y metástasis a distancia / Intimal sarcoma of the pulmonary artery: rare cause of pulmonary hyper tension and metastases

El sarcoma de arteria pulmonar es un tumor infrecuente que afecta en mayor medida a mujeres y con muy mal pronóstico. El diagnóstico suele ser difícil, por su insidioso crecimiento y clínica inespecífica, lo que hace confundir frecuentemente su diagnóstico con una enfermedad tromboembólica pulmonar. Así mismo, ha sido descrito como una causa poco frecuente de hipertensión pulmonar. Presentamos a continuación el caso de una mujer de 66 años de edad, con diagnóstico inicial de tromboembolismo pulmonar (TEP) e hipertensión pulmonar (HTP) secundaria al mismo, siendo diagnosticada finalmente mediante biopsia quirúrgica, de sarcoma intimal de arteria pulmonar. Lo que hace diferente a nuestra paciente con respecto a casos previos es la afectación metastásica a nivel de abdomen, que se objetivó a los pocos meses del diagnóstico definitivo

Intimal sarcoma of the pulmonary artery is a rare tumor that is usually diagnosed during surgery or autopsy. Such tumors are characterized by local growth, with only slight ability to metastasize. Diagnosis is difficult and often delayed owing to the nonspecific nature of the symptoms. Since intimal sarcoma of the pulmonary artery is so rare and insidious it is often confused with pulmonary thromboembolism and is therefore treated inappropriately with prolonged anticoagulation or thrombolysis. With a mean survival of 12 months from the onset of symptoms, the prognosis is poor. We present the case of a woman who was preoperatively diagnosed with intimal sarcoma of the pulmonary artery and who underwent surgical resection with no apparent recurrence at long term follow-up. A review of the literature is also included