Clinical Features Of Chronic Obstructive Pulmonary Disease With Lung Cancer And The Correlation Between Th17-related Cytokines And Lung Cancer Risk

Background and Objectives: Chronic obstructive pulmonary disease(COPD)and lung cancer are leading causes of morbidity and mortality worldwide,and both of these diseases are serious increase in social and economic burden.It is well known that smoking is one of the common risk factors for COPD and lung cancer,and COPD is a major independent risk factor for lung cancer adjusted for smoking.Lung cancer has been assigned as the primary cause of death of patients with mild to moderate COPD.Multiple epidemiological and clinical studies have demonstrated a close link between COPD and lung cancer in pathogenic factors and pathogenesis.The phenotype of COPD based on computed tomography(CT)imaging of the chest has been divided into three types: emphysema,airway obstruction,and mixed type.Several studies suggested that structural emphysema and airway obstruction increased lung cancer risk.However,emphysema is characterized by the destruction of matrix structures,epithelial cell death and a vanishing blood supply;on the contrary,cancer display the ability to avoid apoptosis,proliferate uncontrollably and create new vascular networks.Therefore,in patients with COPD complicated with lung cancer,the relationship between lung cancer location and emphysema in COPD is needed to be explored.The common pathogenesis of COPD and lung cancer has been a hot spot in this field.At present,chronic inflammation has attracted the attention of researchers.COPD is a chronic inflammatory disease of the distal airways,and the severity of COPD is related to local or systemic inflammatory response.In addition,substantial evidence indicated that chronic inflammation can promote tumor initiation.Tumor may occur in areas with chronic inflammation,the longer the duration of inflammation,the higher the risk of tumor development.However,the specific inflammatory cells and cytokines that regulate the origin and progression of both diseases in the same individual are still not clear. T helper 17 cells(Th17)are now widely believed to be critical for the regulation of various autoimmune diseases,and play an important role in tumor immune response.Th17 cells specific secretion of interleukin(IL)-17 played an important role in the regulation of inflammation.A recent study from a mouse model showed the role of Th17 cell in the development of lung cancer,and the expansion of Th17 cells was associated with increased tumor growth in the presence of COPD-type inflammation.Although a lot of observations implicated the involvement of Th17 cells and Th17-related cytokines in the pathogenesis of COPD and lung cancer,the role of Th17-related cytokines in the coexistence of lung cancer and COPD is not clear.Therefore,we conducted a case-control study to explore the relationship between different COPD phenotypes and clinical characteristics of lung cancer based on the clinical data of COPD patients with lung cancer,and to clarify the relationship between lung cancer and emphysema.On the other hand,through the detection of lung cancer patients with or without COPD and healthy controls of the serum levels of Th17-related cytokines,we evaluated the association between Th17-related cytokines and the clinical characteristics of COPD with lung cancer.Methods: Part I: Different phenotypes of chronic obstructive pulmonary disease based on chest CT and clinical features of lung cancer: a correlation analysis Through a retrospective case-control study,the data of clinical-pathological information were collected from COPD with lung cancer patients.Based on chest CT,COPD complicated with lung cancer patients classified as emphysema group or airway obstructive group,and emphysema score.The relationship between the two groups of clinical features was analyzed.In addition,the patients of emphysema group were divided into tumor near emphysema group and away from emphysema group,and to evaluation the association between tumor location and severity of emphysema.Part II: Association between Th17-related cytokines and chronic obstructive pulmonary disease with lung cancer Conducting a case-control study design,218 NSCLC patients(70 with COPD were defined COPD group and 148 without COPD were defined non-COPD group)were compared to 148 healthy controls,which matched non-COPD patients on age,gender and smoking status(current,former,never).The data of clinical-pathological features of these participants were collected.Serum levels of Th17-related cytokines that include IL-17 A,IL-17 F,IL-22,IL-23,and tumor necrosis factor-α(TNF-α)were measured using a Luminex assay.Results: Part I: 1.Most of patients with COPD with lung cancer were male,the central squamous cell carcinoma and late-stage.2.The age,percentage of males and smoking index in emphysema group were higher than that of airway obstructive group,and the body mass index(BMI),ratio of forced expiratory volume in 1 second(FEV1.0)to forced vital capacity(FVC),percentage FEV1.0(FEV1.0%pred)were lower than that of airway obstructive group(P<0.05).3.Spearman’s correlation analysis showed a positive correlation between smoking index and emphysema score(P<0.05);FEV1.0/FVC,FEV1%pred and emphysema score was negatively correlated(P<0.05).4.In patients of emphysema group,the proportion of tumor location away from the emphysema was higher(69.1%),but with the increase in the severity of emphysema,lesions near the emphysema patients increased(P<0.05),and peripheral adenocarcinoma more likely to developed near emphysema.Part II: 1.Compared with the patients in the non-COPD group and healthy control group,patients in COPD group were significantly older,more males,and more smokers(P<0.05);SCC was the most frequent histological type in the COPD group,whereas non-SCC,especially adenocarcinoma,was more frequent in the non-COPD group(P<0.05).There were less patients with stage IV NSCLC in the COPD group than that in the non-COPD group(P<0.05).2.The serum levels of IL-17 A,IL-17 F,IL-22,IL-23 and TNF-α were significant higher in the NSCLC patients,regardless of whether they had COPD,than in the healthy controls(P<0.05).However,no significant differences were found between NSCLC patients with COPD and patients without COPD(P>0.05).3.In the subgroup analysis,the levels of Th17-related cytokines were found in a consistently higher in the I-IIIa stage than the IIIb-IV stage in non-COPD group(P<0.05).4.Increasing serum levels of Th17-related cytokines were associated with an increasing risk of NSCLC,adjusted for age,sex and smoking status(P<0.05).5.The five Th17-related cytokines(IL-17 A,IL-17 F,IL-22,IL-23,and TNF-α)had pair-wise correlations with Spearman’s rank correlation coefficients of 0.646-0.888(P<0.05).Conclusions: 1.Most of patients with COPD with lung cancer were male,the central squamous cell carcinoma and late-stage.2.In patients with COPD with lung cancer,most of tumor location away from the emphysema,but with the increase in the severity of emphysema,lesions near the emphysema patients increased,and peripheral adenocarcinoma more likely to developed near emphysema.3.Serum levels of Th17-related cytokines were consistently elevated in the patients with NSCLC,supporting a strong association between Th17-related inflammation and NSCLC patients complicated with or without COPD.4.The elevated level of Th17-related cytokines was an independent risk factor for lung cancer.