ABSTRACT
The correct understanding of tumour development relies on the comprehensive study of proteins. They are the main orchestrators of vital processes, such as signalling pathways, which drive the carcinogenic process. Proteomic technologies can be applied to cancer research to detect differential protein expression and to assess different responses to treatment. Lung cancer is the number one cause of cancer-related death in the world. Mostly diagnosed at late stages of the disease, lung cancer has one of the lowest 5-year survival rates at 15 %. The use of different proteomic techniques such as two-dimensional gel electrophoresis (2D-PAGE), isotope labelling (ICAT, SILAC, iTRAQ) and mass spectrometry may yield new knowledge on the underlying biology of lung cancer and also allow the development of new early detection tests and the identification of changes in the cancer protein network that are associated with prognosis and drug resistance (AU)
Subject(s)
Humans , Male , Female , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/radiotherapy , Survivorship/psychology , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/secondaryABSTRACT
Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. The aim of this study was to identify distinct proteomic profiles able to discriminate these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC without COPD, and control with neither COPD nor LC. Proteins were separated into spots by bidimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 40 proteins were differentially expressed in the LC and/or COPD groups as compared with the control group. Distinct protein profiles were identified and validated for each pathological entity (LC and COPD). The main networks involved were related to inflammatory signalling, free radical scavenging and oxidative stress response, and glycolysis and gluconeogenesis pathways. The most relevant signalling link between LC and COPD was through the NF-κB pathway. In conclusion, the protein profiles identified contribute to elucidate the underlying pathogenic pathways of both diseases, and provide new tools of potential use as biomarkers for the early diagnosis of LC. BIOLOGICAL SIGNIFICANCE: Sequence coverage. The protein sequence coverage (95%) was estimated for specific proteins by the percentage of matching amino acids from the identified peptides having confidence greater than or equal to 95% divided by the total number of amino acids in the sequence. Ingenuity Pathways Analysis. Mapping of our proteins onto biological pathways and disease networks demonstrated that 22 proteins were linked to inflammatory signalling (p-value: 1.35 10(-08)-1.42 10(-02)), 15 proteins were associated with free radical scavenging and oxidative stress response (p-value: 4.93 10(-11)-1.27 10(-02)), and 9 proteins were related with glycolysis and gluconeogenesis pathways (p-value: 7.39 10(-09)-1.58 10(-02)).
Subject(s)
Biomarkers, Tumor/metabolism , Lung Neoplasms/metabolism , Neoplasm Proteins/metabolism , Proteomics , Pulmonary Disease, Chronic Obstructive/metabolism , Adult , Aged , Aged, 80 and over , Electrophoresis, Gel, Two-Dimensional , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/pathology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
The correct understanding of tumour development relies on the comprehensive study of proteins. They are the main orchestrators of vital processes, such as signalling pathways, which drive the carcinogenic process. Proteomic technologies can be applied to cancer research to detect differential protein expression and to assess different responses to treatment. Lung cancer is the number one cause of cancer-related death in the world. Mostly diagnosed at late stages of the disease, lung cancer has one of the lowest 5-year survival rates at 15 %. The use of different proteomic techniques such as two-dimensional gel electrophoresis (2D-PAGE), isotope labelling (ICAT, SILAC, iTRAQ) and mass spectrometry may yield new knowledge on the underlying biology of lung cancer and also allow the development of new early detection tests and the identification of changes in the cancer protein network that are associated with prognosis and drug resistance.
Subject(s)
Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Lung Neoplasms/metabolism , Proteomics/methods , Electrophoresis, Gel, Two-Dimensional , Humans , Isotope Labeling , Mass Spectrometry , ProteomeABSTRACT
Differently metalated vinylcuprate intermediates resulting from silyl- or stannylcupration of silyl- and tin-containing acetylenes reacted with a range of electrophiles, including chlorosilanes and chlorostannanes, affording regio- and stereodefined differently metalated vic and gem silyl- and tin-trisubstituted alkenes. Some of these functionalized polymetalated olefins are interesting synthons in organic chemistry.
