Effect Of Chronic Obstructive Pulmonary Disease On Lung Microbiome In Lung Cancer Patients

Background:Lung cancer and chronic obstructive pulmonary disease(COPD)are common respiratory diseases.Previous studies had shown that COPD increased the risk factor of lung cancer.Also,the overall survival rates of lung cancer patients with COPD were lower than those without.However,there are few studies focusing on the relationship of the lung microbiome between these two diseases.In addition,the lung cancer in never-smoking people especially in female group is considered as a unique disease,but little relative research had been carried on the lung microbiome of these people.Objective:To investigate the difference between the lung microbiome in lung cancer patients with COPD and those without.To explore whether COPD influences the difference between the lung microbiome in lung adenocarcinoma and squamous cell lung carcinoma patients.To explore whether COPD influences the difference between the lung microbiome in lung cancer patients with distant metastasis and without distant metastasis.To characterize lung microbiome of lung cancer patients in female never-smokers.Methods:We collected bronchial washing fluids(BWF)samples from 40 newly diagnosed lung cancer patients,spontaneous sputum samples from 96 patients with newly diagnosed lung cancer and 5 patients with benign lung diseases Bacterial species of BALF samples and sputum samples were sequenced via 16S rRNA sequencing with V3-V4 region.Bioinformatics and statistical methods were used to compare the lung microbiome differences between target groups.Results:The bacterial diversity in BWF of lung cancer patients with COPD(WC)was higher than that of those without COPD(NC),which was not seen in sputum group.Compared with NC patients,the relative abundance of Haemophilus,Oribacterium,Bulleidia,Abiotrophia,Atopobium and Granulicatella in WC patients were significantly higher in BWF group,while the relative abundance of Olsenella and Scardovia were significantly higher,Capnocytophaga lower in WC patients in sputum group.In the male smoker lung patients with COPD,the relative abundance of Eubacterium in the sputum in squamous cell carcinoma(SCC-WC)was significantly higher than that in Lung adenocarcinoma patients.In the male smoker lung cancer patients without COPD,However,the relative abundance of Cryptobacterium in the sputum in squamous cell carcinoma(SCC-NC)was significantly higher and Campylobacter lower than that in Lung adenocarcinoma patients(AD-NC).In the male smoker lung cancer patients with COPD,the relative abundance of Gemella in the sputum in those with distant metastasis were significantly higher than those in patients without distant metastasis.While in male smoker lung cancer patients without COPD,the relative abundance of Aquificae and Hydrogenobaculum in the sputum in those with distant metastasis were significantly lower than those in patients without distant metastasis.Compared with MN patients,the relative abundance of Oribacterium,Peptococcus,Actinobacillus and Pseudoramibacter_Eubacterium in the BWF of FN patients were significantly higher and Novosphingobium lower.Both the bacterial diversity of the sputum in FN and MS patients were significantly higher than that in MN patients,and they had no significant difference,which indicated the bacterial diversity of the sputum in FN patients was similar to that of MS patients.Compared with lung benign disease(BN),the relative abundance of Dichelobacter and Chryseobacterium in the sputum of FN patients were significantly higher and Haemophilus and Aggregatibacter lower.Compared with lung benign disease(BN)at the same time,the relative abundance of Dichelobacter in the sputum of MS patients was significantly higher and Haemophilus and Aggregatibacter lower.The differential genus in the sputum between the FN and BN group were 3/4 the same to those between the MS and BN group,suggesting that the characteristic in FN patients was similar to that of the MS patients.Conclusions:COPD may have effect on the lung microbiome of lung cancer patients.Further research showed that COPD was associated with the difference of the lung microbiome between lung adenocarcinoma and lung squamous cell carcinoma,and that between lung cancer with distant metastasis and those without.The characteristic of lung microbiome of lung cancer patients in never smoking patients existed gender differences.The characteristic of lung microbiome of lung cancer patients in female never-smokers may be similar to that in male smokers.