scholarly journals Multi-omic molecular profiling of lung cancer in COPD

2018 ◽  
Vol 52 (1) ◽  
pp. 1702665 ◽  
Author(s):  
Brian J. Sandri ◽  
Adam Kaplan ◽  
Shane W. Hodgson ◽  
Mark Peterson ◽  
Svetlana Avdulov ◽  
...  

Chronic obstructive pulmonary disease (COPD) is a known risk factor for developing lung cancer but the underlying mechanisms remain unknown. We hypothesise that the COPD stroma contains molecular mechanisms supporting tumourigenesis.We conducted an unbiased multi-omic analysis to identify gene expression patterns that distinguish COPD stroma in patients with or without lung cancer. We obtained lung tissue from patients with COPD and lung cancer (tumour and adjacent non-malignant tissue) and those with COPD without lung cancer for profiling of proteomic and mRNA (both cytoplasmic and polyribosomal). We used the Joint and Individual Variation Explained (JIVE) method to integrate and analyse across the three datasets.JIVE identified eight latent patterns that robustly distinguished and separated the three groups of tissue samples (tumour, adjacent and control). Predictive variables that associated with the tumour, compared to adjacent stroma, were mainly represented in the transcriptomic data, whereas predictive variables associated with adjacent tissue, compared to controls, were represented at the translatomic level. Pathway analysis revealed extracellular matrix and phosphatidylinositol-4,5-bisphosphate 3-kinase–protein kinase B signalling pathways as important signals in the tumour adjacent stroma.The multi-omic approach distinguishes tumour adjacent stroma in lung cancer and reveals two stromal expression patterns associated with cancer.

2021 ◽  
Author(s):  
Amirhossein Fathinavid ◽  
Zaynab Mousavian ◽  
Ali Najafi ◽  
Ali Masoudi-Nejad

Abstract Background: The association between lung cancer and chronic obstructive pulmonary disease (COPD) is now well established; as people with COPD are more likely to develop lung carcinoma. However, the evidence for this relationship is inconclusive and there is currently little information on the underlying molecular mechanisms. MicroRNAs (miRNAs) are one of the regulatory factors in lung cancer and COPD that their functions are widely studied in many chronic diseases and cancers. Rationally, determining common miRNAs for both of diseases could provide a more detailed picture of this association and the involved molecular mechanisms. In this study, we applied systems biology approaches to identify and predict miRNAs that potentially play regulatory roles between COPD and lung cancer. Results: We performed differential expression analysis on public miRNA and mRNA expression data sets, for both of diseases, and calculated two correlation matrices between miRNA and mRNA for case and control samples. Then we constructed two miRNA-mRNA co-expression networks and merged these two co-expression networks into a community co-expression network. Results indicated the existence of very common miRNAs (ex. hsa-miR-326 and hsa-miR-1293) and mRNAs (such as FAT2, ALOX5AP, and LDB2) between the two mentioned diseases. Moreover, we discovered specific miRNAs (hsa-miR-574-3p) that targeted common mRNAs. We utilized drug-target interaction networks to identify candidate drugs (e.g. iloperidone) for common mRNAs that could be considered in treatment both of diseases.Conclusions: Generally, our study highlighted common miRNAs between COPD and lung cancer that could be used as new signatures or biomarkers for therapeutic purposes. Moreover, discovered candidate drugs may be applied in the treatment of both mentioned diseases. Investigating the miRNA biomarkers in this study improves our understanding about the shared mechanisms between COPD and lung cancer.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
V. Conti ◽  
G. Corbi ◽  
V. Manzo ◽  
G. Pelaia ◽  
A. Filippelli ◽  
...  

Chronic Obstructive Pulmonary disease (COPD) is an inflammatory syndrome that represents an increasing health problem, especially in the elderly population. Drug therapies are symptomatic and inadequate to contrast disease progression and mortality. Thus, there is an urgent need to clarify the molecular mechanisms responsible for this condition in order to identify new biomarkers and therapeutic targets. Processes including oxidant/antioxidant, protease/antiprotease, and proliferative/antiproliferative balance and control of inflammatory response become dysfunctional during aging as well as in COPD. Recently it was suggested that Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to oxidative stress and chronic inflammation, is implicated in both development and progression of COPD. The present review focuses on the involvement of SIRT1 in the regulation of redox state, inflammation, and premature senescence, all crucial characteristics of COPD phenotypes. Recent evidence corroborating the statement of the “aging theory for COPD” was also discussed.


Author(s):  
Surabhi Gautam ◽  
Rima Dada

Complex chronic lifestyle disorders are the leading causes of death and disability worldwide. Stress and anxiety associated with today's hectic life schedule and polluted environment have contributed a lot in triggering and causing many chronic diseases and decreased quality of life, even with pharmacologic treatment. Most of the chronic complex diseases, such as chronic obstructive pulmonary disease, depression, autoimmune diseases, cancer, cardiovascular diseases, obesity, and diabetes mellitus share underlying mechanisms like high levels of stress, anxiety, depression, oxidative stress, shorter telomeres, persistent activation of hypothalamo-pituitary adrenal axis, inflammation and dysregulated immune system, and thus need to be managed by an integrated approach that targets both mind and body. The individuals with these conditions have been reported to benefit from yoga, but the underlying mechanism of action of yoga remains unclear. The aim of this chapter is to summarize the mechanism of action underlying the cumulative effect of yoga on multiple pathways at a cellular level.


Author(s):  
Kevin Baßler ◽  
Wataru Fujii ◽  
Theodore S. Kapellos ◽  
Arik Horne ◽  
Benedikt Reiz ◽  
...  

AbstractDespite the epidemics of chronic obstructive pulmonary disease (COPD), the cellular and molecular mechanisms of this disease are far from being understood. Here, we characterize and classify the cellular composition within the alveolar space and peripheral blood of COPD patients and control donors using a clinically applicable single-cell RNA-seq technology corroborated by advanced computational approaches for: machine learning-based cell-type classification, identification of differentially expressed genes, prediction of metabolic changes, and modeling of cellular trajectories within a patient cohort. These high-resolution approaches revealed: massive transcriptional plasticity of macrophages in the alveolar space with increased levels of invading and proliferating cells, loss of MHC expression, reduced cellular motility, altered lipid metabolism, and a metabolic shift reminiscent of mitochondrial dysfunction in COPD patients. Collectively, single-cell omics of multi-tissue samples was used to build the first cellular and molecular framework for COPD pathophysiology as a prerequisite to develop molecular biomarkers and causal therapies against this deadly disease.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Cassandra P. Nader ◽  
Aylin Cidem ◽  
Nicole M. Verrills ◽  
Alaina J. Ammit

Abstract Lung cancer (LC) has the highest relative risk of development as a comorbidity of chronic obstructive pulmonary disease (COPD). The molecular mechanisms that mediate chronic inflammation and lung function impairment in COPD have been identified in LC. This suggests the two diseases are more linked than once thought. Emerging data in relation to a key phosphatase, protein phosphatase 2A (PP2A), and its regulatory role in inflammatory and tumour suppression in both disease settings suggests that it may be critical in the progression of COPD to LC. In this review, we uncover the importance of the functional and active PP2A holoenzyme in the context of both diseases. We describe PP2A inactivation via direct and indirect means and explore the actions of two key PP2A endogenous inhibitors, cancerous inhibitor of PP2A (CIP2A) and inhibitor 2 of PP2A (SET), and the role they play in COPD and LC. We explain how dysregulation of PP2A in COPD creates a favourable inflammatory micro-environment and promotes the initiation and progression of tumour pathogenesis. Finally, we highlight PP2A as a druggable target in the treatment of COPD and LC and demonstrate the potential of PP2A re-activation as a strategy to halt COPD disease progression to LC. Although further studies are required to elucidate if PP2A activity in COPD is a causal link for LC progression, studies focused on the potential of PP2A reactivating agents to reduce the risk of LC formation in COPD patients will be pivotal in improving clinical outcomes for both COPD and LC patients in the future.


Author(s):  
Melvin K Mathews ◽  
Abubaker Siddiq ◽  
Bharathi D R

Background: Chronic obstructive pulmonary disease (COPD) is preventable and treatable disease state characterized by air flow limitation that is not fully reversible. Severity of the symptoms is increased during exacerbations. Objectives: The purpose of the study is to assess and improve the knowledge regarding COPD among study subjects. Materials and Methods: A Cross-sectional interventional study was carried out among the peoples in selected areas of the Chitradurga city for a period of six months. Result: A total 207 subjects enrolled in the study in that 155 male and 52 females. In our study mean score of post test was more (5.87±1.68) when compare to pre-test (2.63±1.46) which show significant increase in their knowledge after educating them (p=0.000). A total of 207 subjects were enrolled into the study. SPSS Software was used to calculate the statistical estimation. Paired t-test was used to detect the association status of different variables. Conclusion: The relatively good level of COPD awareness needs to be maintained to facilitate future prevention and control of the disease. This study had identified that negative illness perceptions should be targeted, so that they will not avoid patients from seeking for COPD treatment and adhere to it. Key words: Cross sectional study, Knowledge, practice, COPD.


Author(s):  
Gavin H. West ◽  
Laura S. Welch

This chapter describes the hazards for construction workers, with a particular focus on injuries as well as exposures to hazardous chemicals and dusts. A section describes hazardous exposures to lead and other heavy metals. Another section describes noise exposure. The impact of musculoskeletal disorders among construction workers is then discussed. A section on respiratory diseases focuses on asbestosis, silicosis, chronic obstructive pulmonary disease, and asthma. Exposures known to cause dermatitis and cancer are reviewed. There is a discussion of engineered nanomaterials as a potential emerging hazard. Various approaches to prevention and control, including regulations and health services, are described.


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