The Correlation Study Of Microbiota In The Diagnosis And Chemotherapy For Locally Advanced Or Advanced Lung Cancer

The value and correlation of microbiota in the diagnosis for locally advanced or advanced lung cancerBackground:The human microbiota is a complex ecosystem composed of mainly bacteria,viruses and fungi that inhabit the human mouth,lung,and intestines.Changes such as microbial disorders are related to many diseases including malignant tumors.However,the role of the microbiota in the occurrence and development of lung cancer is still unclear.At present,there is still a lack of research data on the specific microbiota composition of locally advanced or advanced lung cancer patients in China and the world.This study aims to compare the differences in intestinal and oral flora in locally advanced or advanced lung cancer patients compared to non-tumor populations,for screening key bacteria in the occurrence and development of lung cancer,and discovering microbial biomarkers that assist the diagnosis of locally advanced or advanced lung cancer.Methods:We analyzed stool and oral saliva specimens from the discovery cohort consisted of newly diagnosed locally advanced or advanced lung cancer patients in Cancer Hospital,Chinese Academy of Medical Sciences from September,2018 to September,2019 and their family members without tumor history,through 16S ribosomal ribonucleic acid(16S rRNA)of microbiota.The R statistical programming language was used to analyze the differences in the diversity and composition of the intestinal and oral flora of locally advanced or advanced lung cancer patients compared with non-tumor populations.The random forest machine learning 10-fold cross-validation method was used to construct the model of intestinal and salivary flora that assisted the diagnosis of lung cancer,and validated in the validation cohort.Results:A total of 60 newly diagnosed locally advanced or advanced lung cancer patients and 35 non-tumor population controls were included in the discovery cohort.Compared with the non-tumor populations,the a diversity of salivary microflora was significantly decreased in lung cancer patients,and the compositions of salivary and intestinal microflora were significantly changed.Using the 10-fold cross-validation method,in terms of saliva flora,it was found that the prediction model with 10 microbial species biomarkers based on the operational taxonomic unit(OTU)has high accuracy in the prediction of lung cancer,with the area under the curve(AUC)as 85%,sensitivity and specificity reaching 82%and 99%,respectively.In terms of intestinal flora,another prediction model based on OTU-based 10 microbial species biomarkers can also assist in the diagnosis of lung cancer(AUC=78%,sensitivity=65%,specificity=99%).To verify the findings of the discovery cohort,we recruited another independent cohort consisting of 41 lung cancer patients and 26 non-tumor control groups as the verification cohort.In the verification cohort,the prediction accuracy of the salivary flora prediction lung cancer model was 77%,and the sensitivity and specificity were 53%and 95%,respectively;the intestinal flora model had a prediction accuracy of 67%,with the sensitivity and specificity as 47%and 86%,respectively.Conclusions:Patients with locally advanced or advanced lung cancer have the special microbiota profile compared to non-tumor populations,and the specific intestinal and salivary microbiota biomarker models can be used to assist in the potential predictive diagnosis of lung cancer.The correlation study of gut microbiome in the clinical efficacy and survival benefits of first-line chemotherapy for patients with locally advanced or advanced lung cancerBackground:Accumulating evidences have disclosed the important role of gut microbiome in modulating response of immunotherapy in the patients with lung cancer.However,research exploring the relationship of intestinal flora and chemotherapy is still limited.The study is to investigate the correlation between intestinal flora and chemotherapy efficacy and survival benefits in locally advanced or advanced lung cancer,preliminarily exploring non-innovative intestinal microbial biomarkers to predict the clinical outcomes of first-line chemotherapy.Methods:We analyzed baseline stool samples from patients with locally advanced or advanced lung cancer before chemotherapy treatment in Cancer Hospital,Chinese Academy of Medical Sciences from September,2018 to September,2019,through metagenomics of gut microbiota.The diversity,composition,function and metabolic pathway of microbial communities were compared among patients with different chemotherapy outcomes.Results:64 consecutive patients with locally advanced or advanced lung cancer treated with chemotherapy were included into this study.All patients provided the stool samples.33 of 64 patients responded to treatment(responders)and another 31 patients didn’t(non-responders).The median progression-free survival was 7 months(range,1.5-14.5).Streptococcus mutans(P=0.026)and Enterococcus casseliflavus(P=0.049)were enriched in responders,while 11 bacteria including Leuconostoc lactis(P=0.002)and Eubacterium siraeum(P=0.006)were enriched in non-responders.Functional analysis of metabolic pathways revealed that L-glutamate degradation VIII pathway was enriched in responders(P=0.014),and C4 photosynthetic carbon assimilation cycle,reductive TCA cycle I,and hexitol fermentation to lactate,formate,ethanol and acetate were enriched in non-responders(P<0.05).On the other hand,12 species were statistically significantly different among the progression-free survival benefit groups.Patients enriched with 6 bacterial species,such as Roseburia inulinivorans(P=0.004),and Streptococcus mutans(P=0.048)had longer progression-free survival than those enriched in the other 6 bacteria including Prevotella stercorea,Akkermansia muciniphila,Lactobacillus johnsonii,Alistipes indistinctus,Streptococcus intermedius and Butyrivibrio crossotus(P<0.05).Purine nucleobases degradation I and other 4 metabolic pathways were enriched in lung cancer patients with longer progression-free survival(P<0.05).In addition,significant associations of certain bacterial species with clinical parameters such as age,body mass index(BMI),pathological pattern and metastatic sites were observed by spearman correlation analysis.Conclusions:Specific intestinal bacteria may be associated with the clinical outcomes such as efficacy and survival benefits of locally advanced or advanced lung cancer patients with chemotherapy,which may be the potential biomarkers to predict the chemotherapy outcomes.