Sleep apnoea increases biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk patients and those with established lung cancer

Intermittent hypoxaemia and obstructive sleep apnoea (OSA) have been linked to lung cancer through as yet unidentified pathophysiological mechanisms. This study evaluates the effect of OSA on serum levels of biomarkers of immunosurveillance, lymphangiogenesis and intrinsic tumour cell aggressiveness in high-risk individuals screened for lung cancer and patients with established lung cancer. Serum samples from individuals participating in a lung cancer screening cohort (SAILS study) or with newly diagnosed lung cancer (SAIL study) were analysed. All patients underwent home sleep apnoea testing. Soluble levels of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PDL1), cytotoxic T-lymphocyte antigen-4, midkine (MDK), paraspeckle component-1 (PSPC1), transforming growth factor-β1 (TGF-β1), SMAD3, matrix metalloproteinase-2 and co-stimulus receptor of the tumour necrosis factor family of receptors (CD137) were determined by ELISA. The presence of moderate-to-severe OSA was associated with increased levels of PSPC1, MDK, PD-L1 and PD-1 in screened individuals, and with higher values of PSPC1, TGF-β1, PD-L1 and PD-1 in patients with established lung cancer. The findings correlated with nocturnal intermittent hypoxaemia indices. Moderate-to-severe OSA is associated with increased expression of serum biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk individuals screened for lung cancer and those with established diseaseThis study was supported by grants from Instituto de Salud Carlos III (ISCIII) PI19/01612, PI22/01262 and P2022/BMD-7224 to F. García-Río, CP18/00028, PI19-01363 and PI22/01257 to C. Cubillos-Zapata, PI20/01416 to L.M. Seijo and G. Peces-Barba; a grant from the Spanish Thoracic Society (SEPAR) to L.M. Seijo; and cofunded by the European Union, Ayudas Luis Alvarez 2021 FIBHULP. Funding information for this article has been deposited with the Crossref Funder Registr

Heteroatom-tagged proteomics of lung cancer and chronic obstructive pulmonary disease human serum reveal alterations in selenoproteins

Heteroatom-tagged proteomics allows the absolute quantification of selenoproteins using the heteroatom as a "tag" into a selective and sensitive atomic detector instead of a molecular one. Using this analytical method, about 90% of total selenium in human serum/plasma can be measured as selenoproteins and total selenometabolites and thus, the status of selenium can be determined. Herein, we determined the absolute concentration of selenoproteins in human serum patients with lung cancer (LC) and chronic obstructive pulmonary disease (COPD), a competing cause of morbidity and mortality in smokers as well as an independent risk factor for LC. We conducted an observational study of 154 human serum samples obtained from LC and COPD patients with varying severity of disease, including COPD patients who developed LC during follow-up and healthy controls (HC). Using heteroatom-tagged proteomics, we determined extracellular glutathione peroxidase (eGPx), selenoprotein P (SELENOP), and selenoalbumin (SeAlb). Associations between selenoproteins were also studied as potential biomarkers of disease. The concentration of eGPx was significantly higher in the all-inclusive COPD cohort compared to HC, COPD patients with LC, or those with mild obstructive lung disease, while SELENOP concentration was significantly decreased in LC patients compared to HC and COPD. We found an inverse correlation between SELENOP and SeAlb in HC, but also in LC patients, and especially in patients with COPD and LC. Moreover, we found that eGPx and selenometabolite concentrations were positively associated with LC human serum. Selenoprotein concentrations were altered in COPD and LC when compared to healthy controls suggesting a potential role of the selenoproteome in the diagnosis and/or treatment of these tobacco-related diseases.Funding: This work has been supported by the project “Heteroatom-tagged proteomics and metabolomics to study lung cancer. Influence of gut microbiota” (Ref.: PY20_00366). Project of Excellence. Regional Ministry of Economy, Knowledge, Business and University, Andalusia, Spain. The authors also thank the grants Ref. 651/2018 and 115/2020 from the Spanish Society of Pneumology and Surgery (SEPAR) and 08/2018 from the Association of Pneumology and Thoracic Surgery (Neumosur) that supported samples recruitment at the hospitals and biobank registration. The authors also thank Instituto de Salud Carlos III (AES16/01783) and unrestricted funding from Menarini Group and AstraZeneca“. Funding for open access charge: Universidad de Huelva / CBUA. Acknowledgements: We thank all the patients who have volunteered and donated their biomaterials for the study

Untargeted Metabolomic Study of Lung Cancer Patients after Surgery with Curative Intent

© 2023 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0.Lung cancer (LC) is a leading cause of mortality, claiming more than 1.8 million deaths per year worldwide. Surgery is one of the most effective treatments when the disease is in its early stages. The study of metabolic alterations after surgical intervention with curative intent could be used to assess the response to treatment or the detection of cancer recurrence. In this study, we have evaluated the metabolomic profile of serum samples (n = 110) from preoperative (PRE) and postoperative (POST) LC patients collected at two different time points (1 month, A; 3–6 months, B) with respect to healthy people. An untargeted metabolomic platform based on reversed phase (RP) and hydrophilic interaction chromatography (HILIC), using ultra-high performance liquid chromatography (UHPLC) and mass spectrometry (MS), was applied (MassIVE ID MSV000092213). Twenty-two altered metabolites were annotated by comparing all the different studied groups. DG(14,0/22:1), stearamide, proline, and E,e-carotene-3,3′-dione were found altered in PRE, and their levels returned to those of a baseline control group 3–6 months after surgery. Furthermore, 3-galactosyllactose levels remained altered after intervention in some patients. This study provides unique insights into the metabolic profiles of LC patients after surgery at two different time points by combining complementary analytical methods.This work has been supported by the project “Heteroatom-tagged proteomics and metabolomics to study LC. Influence of gut microbiota' (Ref.: PY20_00366). Project of Excellence. Regional Ministry of Economy, Knowledge, Business and University, Andalusia, Spain. The authors also thank the grants Ref. 651/2018 and 115/2020 from the Spanish Society of Pneumology and Surgery (SEPAR) and 08/2018 from the Association of Pneumology and Thoracic Surgery (Neumosur) that supported sample recruitment at the hospitals and biobank registration. The authors also thank the Instituto de Salud Carlos III (AES16/01783) and unrestricted funding from the Menarini Group. Funding for open access charge: Universidad de Huelva/CBUA.Peer reviewe

Supplementary Material Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary Disease

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).--Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.This work has been supported by the project “Heteroatom-tagged proteomics and metabolomics to study lung cancer. Influence of gut microbiota” (Ref.: PY20_00366) (Project of Excellence, Regional Ministry of Economy, Knowledge, Business and University, Andalusia, Spain). The authors are also grateful for grants 651/2018 and 115/2020 from the Spanish Society of Pneumology and Surgery (SEPAR) and grant 08/2018 from the Association of Pneumology and Thoracic Surgery (Neumosur), which were used to facilitate recruitment at the hospitals and biobank registration. The authors also thank Instituto de Salud Carlos III (AES16/01783) and wish to express their gratitude for the unrestricted funding from the Menarini Group and AstraZeneca.Peer reviewe

Heteroatom-tagged proteomics of lung cancer and chronic obstructive pulmonary disease human serum reveal alterations in selenoproteins

Heteroatom-tagged proteomics allows the absolute quantification of selenoproteins using the heteroatom as a “tag” into a selective and sensitive atomic detector instead of a molecular one. Using this analytical method, about 90% of total selenium in human serum/plasma can be measured as selenoproteins and total selenometabolites and thus, the status of selenium can be determined. Herein, we determined the absolute concentration of selenoproteins in human serum patients with lung cancer (LC) and chronic obstructive pulmonary disease (COPD), a competing cause of morbidity and mortality in smokers as well as an independent risk factor for LC. We conducted an observational study of 154 human serum samples obtained from LC and COPD patients with varying severity of disease, including COPD patients who developed LC during follow-up and healthy controls (HC). Using heteroatom-tagged proteomics, we determined extracellular glutathione peroxidase (eGPx), selenoprotein P (SELENOP), and selenoalbumin (SeAlb). Associations between selenoproteins were also studied as potential biomarkers of disease. The concentration of eGPx was significantly higher in the all-inclusive COPD cohort compared to HC, COPD patients with LC, or those with mild obstructive lung disease, while SELENOP concentration was significantly decreased in LC patients compared to HC and COPD. We found an inverse correlation between SELENOP and SeAlb in HC, but also in LC patients, and especially in patients with COPD and LC. Moreover, we found that eGPx and selenometabolite concentrations were positively associated with LC human serum. Selenoprotein concentrations were altered in COPD and LC when compared to healthy controls suggesting a potential role of the selenoproteome in the diagnosis and/or treatment of these tobacco-related diseases.This work has been supported by the project “Heteroatom-tagged proteomics and metabolomics to study lung cancer. Influence of gut microbiota” (Ref.: PY20_00366). Project of Excellence. Regional Ministry of Economy, Knowledge, Business and University, Andalusia, Spain. The authors also thank the grants Ref. 651/2018 and 115/2020 from the Spanish Society of Pneumology and Surgery (SEPAR) and 08/2018 from the Association of Pneumology and Thoracic Surgery (Neumosur) that supported samples recruitment at the hospitals and biobank registration. The authors also thank Instituto de Salud Carlos III (AES16/01783) and unrestricted funding from Menarini Group and AstraZeneca“. Funding for open access charge: Universidad de Huelva / CBUA.Peer reviewe

Fossil bee cells from the Canary Islands. Ichnotaxonomy, palaeobiology and palaeoenvironments of Palmiraichnus castellanosi

Fossil bee cells, attributable to the ichnospecies Palmiraichnus castellanosi, are recorded from the Pleistocene and Holocene of the easternmost Canary Islands. Cells bear a chamber with internal smooth lining, spiral closure, and an antechamber. They have a discrete wall that surrounds both the chamber and antechamber. The antechamber shows an internal smooth surface and a structureless filling of palaeosol material. These features enable this material to be assigned to the ichnospecies P. castellanosi, originally described from the Palaeogene of Uruguay. This record constitutes the first documented evidence for bees, and Hymenoptera, in the Quaternary of the Canaries and the first for this ichnospecies from Africa. By comparison with extant cells, the potential constructors are bees of the genus Andrena (Andrenidae). Palaeoecological and statistical data suggest that five species may have produced P. castellanosi in the Canary Islands. One on Lanzarote in the Holocene, another in south Fuerteventura in the Upper Pleistocene, two on Gran Canaria and another on Montan&tild;a Clara islet during the Middle Pleistocene. A high level of breeding success was probably favoured by the lack of predators or parasites and optimal environmental conditions, at least in the Pleistocene. During the Pleistocene, the abundance of P. castellanosi in the lowlands suggests a rich endemic shrubby flora and palaeoclimatic conditions similar to the present, but probably with a higher humidity. The land-snail assemblage associated with low densities of P. castellanosi in the Holocene mid-altitude belt suggests a cool moist palaeoenvironment, less favourable for P. castellanosi producers.Fil: La Roche, Francisco. Universidad de La Laguna; EspañaFil: Genise, Jorge Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Castillo, Carolina. Universidad de La Laguna; EspañaFil: Quesada, María Luisa. Universidad de La Laguna; EspañaFil: García Gotera, Cristo M.. Universidad de La Laguna; EspañaFil: De la Nuez, Julio. Universidad de La Laguna; Españ

Metallomic signatures of lung cancer and chronic obstructive pulmonary disease

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.Funding: This work has been supported by the project “Heteroatom-tagged proteomics and metabolomics to study lung cancer. Influence of gut microbiota” (Ref.: PY20_00366) (Project of Excellence, Regional Ministry of Economy, Knowledge, Business and University, Andalusia, Spain). The authors are also grateful for grants 651/2018 and 115/2020 from the Spanish Society of Pneumology and Surgery (SEPAR) and grant 08/2018 from the Association of Pneumology and Thoracic Surgery (Neumosur), which were used to facilitate recruitment at the hospitals and biobank registration. The authors also thank Instituto de Salud Carlos III (AES16/01783) and wish to express their gratitude for the unrestricted funding from the Menarini Group and AstraZeneca. Acknowledgments: We thank all the patients who volunteered and donated their biomaterials for the study

Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary Disease

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC

Untargeted Metabolomic Study of Lung Cancer Patients after Surgery with Curative Intent

Lung cancer (LC) is a leading cause of mortality, claiming more than 1.8 million deaths per year worldwide. Surgery is one of the most effective treatments when the disease is in its early stages. The study of metabolic alterations after surgical intervention with curative intent could be used to assess the response to treatment or the detection of cancer recurrence. In this study, we have evaluated the metabolomic profile of serum samples (n = 110) from preoperative (PRE) and postoperative (POST) LC patients collected at two different time points (1 month, A; 3–6 months, B) with respect to healthy people. An untargeted metabolomic platform based on reversed phase (RP) and hydrophilic interaction chromatography (HILIC), using ultra-high performance liquid chromatography (UHPLC) and mass spectrometry (MS), was applied (MassIVE ID MSV000092213). Twenty-two altered metabolites were annotated by comparing all the different studied groups. DG(14,0/22:1), stearamide, proline, and E,e-carotene-3,3′-dione were found altered in PRE, and their levels returned to those of a baseline control group 3–6 months after surgery. Furthermore, 3-galactosyllactose levels remained altered after intervention in some patients. This study provides unique insights into the metabolic profiles of LC patients after surgery at two different time points by combining complementary analytical methods