Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Eapen, Mathew Suji; Hansbro, Philip M.; Larsson‐Callerfelt, Anna Karin; Jolly, Mohit Kumar; Myers, Stephen; Sharma, Pawan; Jones, Bernard Edward; Rahman, Atiqur; Markos, James; Chia, Collin; Larby, Josie; Haug, Greg; Hardikar, Ashutosh; Weber, Heinrich C.; Mabeza, George; Cavalheri, Vinícius; Khor, Yet H.; McDonald, Christine F; Sohal, Sukhwinder Singh

doi:10.1007/s40265-018-1001-8

Cited by 65 publications

(74 citation statements)

References 319 publications

(354 reference statements)

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“…By comparing the gene expression profiles in lung cancer between nonsmokers and smokers, Woenckhaus et al [33] found PTHLH, being involved in matrix degradation, was differentially expressed, which could reflect early cigarette smoke-induced and cancer-relevant molecular lesions. Chronic obstructive pulmonary disease (COPD) is another threat of smoking-induced lung injury, which can be the driving factor for lung cancer [34]. ATG7, an autophagic gene, is increasingly activated in the early stages of lung injury induced by cigarette smoke [35,36].…”

Section: Discussionmentioning

confidence: 99%

The benefits of smoking cessation on survival in cancer patients by integrative analysis of multi‐omics data

2020

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Few studies have examined the association between smoking status (including former smokers) at diagnosis and overall survival among cancer patients. We aimed to assess the benefits of quitting smoking on cancer prognosis in cohorts of cancer patient smokers obtained from the Cancer Genome Atlas (TCGA) database. Hazard ratios (HR) were calculated to evaluate smoking behavior at cancer diagnosis (reformed smokers vs. current smokers) in association with overall survival using multivariate‐adjusted Cox regressions analysis. According to our analyses, quitting smoking was the independent protective factor for overall survival in lung squamous cell carcinoma (LUSC) (HR = 0.67, 95% CI = 0.48–0.94). Comprehensive analysis of multicomponent data across reformed and current smokers identified a total of 85 differential expressed genes (DEGs) affected by different modes of genetic and epigenetic regulation, potentially representing cancer drivers in smokers. Moreover, we provided a smoking‐associated gene expression signature, which could evaluate the true effect on prognosis with high power (HR = 1.70, 95% CI = 1.19–2.43, AUC = 0.65, 0.67, and 0.70 for 2‐, 3‐, and 5‐year survival, respectively). This signature was also applicable in other smoking‐related cancers, including bladder urothelial carcinoma (HR = 1.70, 95% CI = 1.01–2.88), cervical carcinoma (HR = 5.69, 95% CI = 1.37–23.69), head and neck squamous cell carcinoma (HR = 1.97, 95% CI = 1.41–2.76), lung adenocarcinoma (HR = 1.73, 95% CI = 1.16–2.57), and pancreatic adenocarcinoma (HR = 4.28, 95% CI = 1.47–12.47). In conclusion, this study demonstrates that quitting smoking at diagnosis decreases risk of death in cancer patients. We also provide a smoking‐associated gene expression signature to evaluate the effect of smoking on survival. Lastly, we suggest that smoking cessation could comprise a part of cancer treatment to improve survival rates of cancer patients.

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Section: Discussionmentioning

confidence: 99%

The benefits of smoking cessation on survival in cancer patients by integrative analysis of multi‐omics data

2020

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“…The main causative factors in lung cancer are exposure to carcinogens, cigarette smoke, toxic compounds in the environment/industry, chronic airway inflammation driven by pathogenic infections, and fibrosis/scarring from co-morbid lung disease (30,131). The lung microbiome may be altered by these causative factors and has been linked to lung cancer progression, phenotype and severity.…”

Section: Lung Microbiome and Lung Cancermentioning

confidence: 99%

“…For IPF, international guidelines for the management and treatment are lacking, with patients often limited to the prescription of anti-fibrotic drugs (nintedanib and pirfenidone) and broad spectrum antibiotics (azithromycin and polymyxin) (27,28). For lung cancer, the overall 5-year survival rate was <5% for NSCLC until the last decade when the advent of immunotherapies raised this to 20-30% (29)(30)(31). Unfortunately, only 21% of NSCLC patients and 3.7% of small cell lung cancer patients are eligible for immunotherapy (32).…”

Section: Introductionmentioning

confidence: 99%

Role of Lung Microbiome in Innate Immune Response Associated With Chronic Lung Diseases

et al. 2020

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Respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung fibrosis, and lung cancer, pose a huge socioeconomic burden on society and are one of the leading causes of death worldwide. In the past, culture-dependent techniques could not detect bacteria in the lungs, therefore the lungs were considered a sterile environment. However, the development of culture-independent techniques, particularly 16S rRNA sequencing, allowed for the detection of commensal microbes in the lung and with further investigation, their roles in disease have since emerged. In healthy individuals, the predominant commensal microbes are of phylum Firmicutes and Bacteroidetes, including those of the genera Veillonella and Prevotella. In contrast, pathogenic microbes (Haemophilus, Streptococcus, Klebsiella, Pseudomonas) are often associated with lung diseases. There is growing evidence that microbial metabolites, structural components, and toxins from pathogenic and opportunistic bacteria have the capacity to stimulate both innate and adaptive immune responses, and therefore can contribute to the pathogenesis of lung diseases. Here we review the multiple mechanisms that are altered by pathogenic microbiomes in asthma, COPD, lung cancer, and lung fibrosis. Furthermore, we focus on the recent exciting advancements in therapies that can be used to restore altered microbiomes in the lungs.

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“…By comparing the gene expression profiles in lung cancer between non-smokers and smokers, Woenckhaus et al (36) found PTHLH, being involved in matrix degradation, was differentially expressed, which could reflect early cigarette smoke-induced and cancer-relevant molecular lesions. Chronic obstructive pulmonary disease (COPD) is another threat of smoking-induced lung injury, which can be the driving factor for lung cancer (37). ATG7, an autophagic gene, is increasingly activated in the early stages of lung injury induced by cigarette smoke (38,39).…”

Section: Discussionmentioning

confidence: 99%

The benefits of smoking cessation on survival in cancer patients by integrative analysis of multi-omics data

Yang¹,

Liu²,

Liang³

2020

Preprint

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Background: Few studies have examined the association between smoking cessation at the time of diagnosis and overall survival among cancer patients. We aimed to assess the benefits of quitting smoking on prognosis.Methods: We obtained cohorts of smoking-related cancer patients from the Cancer Genome Atlas (TCGA) database. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated to evaluate smoking behavior at cancer diagnosis (reformed smokers vs. current smokers) in association with overall survival using age and multivariate-adjusted Cox regressions analysis. Comprehensive analysis of multi-component data was carried out to determine the genetic and epigenetic landscape differences and their effects on the differential expression genes (DEGs) between reformed smokers and current smokers. The smoking signature was constructed using univariate Cox regression and LASSO-Cox regression model.Results: According to the multivariate-adjusted Cox regressions analysis, quitting smoking was the independent protective factor for overall survival in lung squamous cell carcinoma (LUSC) (HR=0.67, 95%CI=0.48-0.94). A total of 85 key DEGs were found to be affected by different modes of genetic and epigenetic regulation, which might represent key drivers in smokers. At last, we provided the smoking signature which could predict prognosis with high power (HR=1.70, 95% CI=1.19-2.43, AUC= 0.65, 0.67 and 0.70 for 2, 3 and 5-year survival, respectively). The smoking signature was also applicable in other smoking-related cancers, including bladder urothelial carcinoma (HR=1.70, 95% CI=1.01-2.88), cervical carcinoma (HR=5.69, 95% CI=1.37-23.69), head and neck squamous cell carcinoma (HR=1.97, 95% CI=1.41-2.76), lung adenocarcinoma (HR=1.73, 95% CI=1.16-2.57), and pancreatic adenocarcinoma (HR=4.28, 95% CI=1.47-12.47).Conclusions: The present study demonstrated that quitting smoking at diagnosis decreased risk of death in cancer patients. We also provided the smoking signature to evaluate the true effect of smoking, suggesting that smoking cessation could be a part of cancer treatment to improve the survival rate of cancer patients.

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Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Cited by 65 publications

References 319 publications

The benefits of smoking cessation on survival in cancer patients by integrative analysis of multi‐omics data

The benefits of smoking cessation on survival in cancer patients by integrative analysis of multi‐omics data

Role of Lung Microbiome in Innate Immune Response Associated With Chronic Lung Diseases

The benefits of smoking cessation on survival in cancer patients by integrative analysis of multi-omics data

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