Lung cancer in chronic obstructive pulmonary disease patients. Does cellular senescence matter?

Kuźnar-Kamińska, Barbara; Mikuła-Pietrasik, Justyna; Książek, Krzysztof; Tykarski, Andrzej; Batura‐Gabryel, Halina

doi:10.20452/pamw.4297

Cited by 7 publications

(7 citation statements)

References 51 publications

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“…Senescent cells have been reported in both human and animal models of pulmonary diseases (2,5,6,41,71,107,158,187). Indeed, given that chronologic age is a major risk factor for most chronic diseases, including COPD, asthma, and PF, there is relevance to identifying senescence as a fundamental aging process that, if targeted appropriately, could impact on disease alleviation and overall health in the elderly population.…”

Section: Introductionmentioning

confidence: 99%

Cellular senescence in the lung across the age spectrum

Parikh

Wicher

Khandalavala

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

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Cellular senescence results in cell cycle arrest with secretion of cytokines, chemokines, growth factors, and remodeling proteins (senescence-associated secretory phenotype; SASP) that have autocrine and paracrine effects on the tissue microenvironment. SASP can promote remodeling, inflammation, infectious susceptibility, angiogenesis, and proliferation, while hindering tissue repair and regeneration. While the role of senescence and the contributions of senescent cells are increasingly recognized in the context of aging and a variety of disease states, relatively less is known regarding the portfolio and influences of senescent cells in normal lung growth and aging per se or in the induction or progression of lung diseases across the age spectrum such as bronchopulmonary dysplasia, asthma, chronic obstructive pulmonary disease, or pulmonary fibrosis. In this review, we introduce concepts of cellular senescence, the mechanisms involved in the induction of senescence, and the SASP portfolio that are relevant to lung cells, presenting the potential contribution of senescent cells and SASP to inflammation, hypercontractility, and remodeling/fibrosis: aspects critical to a range of lung diseases. The potential to blunt lung disease by targeting senescent cells using a novel class of drugs (senolytics) is discussed. Potential areas for future research on cellular senescence in the lung are identified.

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Section: Introductionmentioning

confidence: 99%

Cellular senescence in the lung across the age spectrum

Parikh

Wicher

Khandalavala

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Recent studies have revealed that cellular senescence actively contributed to age‐related diseases and tumorigenesis via the senescence‐related secretory phenotype 35 . It has been demonstrated that cellular senescence promoted carcinogenesis in patients with chronic obstructive pulmonary disease 36 . Besides, membrane‐bound CD40L contributed to cellular senescence and activated senescence‐associated secretory phenotype in LUAD 37 .…”

Section: Discussionmentioning

confidence: 99%

“… 35 It has been demonstrated that cellular senescence promoted carcinogenesis in patients with chronic obstructive pulmonary disease. 36 Besides, membrane‐bound CD40L contributed to cellular senescence and activated senescence‐associated secretory phenotype in LUAD. 37 However, the correlation between cellular senescence and RAGE expression has not been investigated.…”

Section: Discussionmentioning

confidence: 99%

RAGE is a potential biomarker implicated in immune infiltrates and cellular senescence in lung adenocarcinoma

Lin

et al. 2022

Clinical Laboratory Analysis

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Background Receptor for Advanced Glycation End‐products (RAGE) is an oncogene abnormally expressed in various cancers. However, the clinical value of RAGE and the biological role of RAGE in lung cancer have not been fully investigated. Methods We compared the RAGE expression using several public databases. The relationship between RAGE expression and clinicopathological variables was assessed. The R software package was used to carry out enrichment analyses of RAGE co‐expression and gene set enrichment analysis (GSEA). Additionally, we used the TIMER database to assess the association between immune infiltration and RAGE expression. The correlation between RAGE expression and senescence biomarkers in lung adenocarcinoma was analyzed using the TCGA database. Results Our findings indicated that the expression of RAGE was downregulated in lung adenocarcinoma, and down‐regulation of RAGE was related to poor overall survival and disease‐free survival. Functional enrichment analysis indicated that RAGE co‐expression genes were mainly associated with neutrophil activation involved in immune response, neutrophil degranulation, and regulation of leukocyte‐mediated immunity. Correlation analysis revealed that RAGE expression was closely related to the purity of the tumor and immune infiltration. GSEA indicated that the RAGE‐related differential genes were mainly enriched in senescence‐related pathways. Besides, the RAGE expression was significantly associated with senescence‐related genes. Conclusion Down‐regulation of RAGE expression was associated with poor prognosis, as well as defective immune infiltration and cellular senescence in lung adenocarcinoma.

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“…Finally, in vitro experiments to better characterize the function of HRG in lung cancer patients, including HRG binding to heparin and fibrin clots [34–36], should be performed in the future. It is also worth investigating whether HRG levels and fibrin properties in lung cancer patients are associated with inflammation and cellular senescence [37].…”

Section: Discussionmentioning

confidence: 99%

Decreased Levels of Histidine-Rich Glycoprotein in Advanced Lung Cancer: Association with Prothrombotic Alterations

et al. 2019

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Background. Histidine-rich glycoprotein (HRG) displays anticoagulant and antifibrinolytic properties in animal models, but its effects in humans are unclear. We investigated serum HRG levels and their associations with the disease stage and prothrombotic alterations in lung cancer (LC) patients. Methods. In 148 patients with advanced LC prior to anticancer therapy (87 non-small-cell LC and 61 small-cell LC) versus 100 well-matched controls, we measured HRG levels in association with clot permeability (Ks), clot turbidimetry (lag phase and maximum absorbance), and clot lysis time (CLT). Results. Compared to controls, LC patients had 45.9% lower HRG levels with no associations with demographics and comorbidities. Decreased HRG, defined as the 90th percentile of control values (<52.7 μg/ml), was 16 times more common in subjects with than without LC (OR=16.4, 95% CI 9.2-23.5, p<0.01). HRG<38 μg/ml discriminated stage IIIAB/limited disease from IV/extensive disease (ED) LC. In LC patients, HRG correlated inversely with CLT (r=−0.41, p<0.001), but not with other fibrin variables. Among stage IV/ED LC, HRG correlated significantly with Ks and lag phase (r=0.28 and r=0.33, respectively, both p<0.001). LC patients with low Ks (10th percentile of control values) combined with prolonged CLT (90th percentile of control values) had reduced HRG levels compared to the remainder (p=0.003). No such observations were noted in controls. Conclusions. Our study is the first to show that decreased HRG levels occur in advanced LC and are associated with the disease stage and hypofibrinolysis.

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Lung cancer in chronic obstructive pulmonary disease patients. Does cellular senescence matter?

Abstract: Prevention and early detection of lung cancer in patients with chronic obstructive pulmonary disease: screening programs and reducing exposure to risk factors Given that COPD favors carcinogene sis in the respiratory system, there is a need to

Cited by 7 publications

References 51 publications

Cellular senescence in the lung across the age spectrum

Cellular senescence in the lung across the age spectrum

RAGE is a potential biomarker implicated in immune infiltrates and cellular senescence in lung adenocarcinoma

Decreased Levels of Histidine-Rich Glycoprotein in Advanced Lung Cancer: Association with Prothrombotic Alterations

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