Study On Biomarkers Of Lung Cancer Based On Microbiomics And Metabolomics

Background: lung cancer has the characteristics of high incidence rate and high mortality,which seriously endangers human life and health.Many early-stage lung cancer patients have no symptom or mild symptoms with no specificity,making it difficult to attract attention.The imbalance of intestinal microorganisms is considered to be related to the diagnosis,treatment and prognosis of a variety of diseases.At present,many studies involve the sequencing of intestinal microorganisms in patients with lung cancer.However,little is known about the interplay between intestinal microbiome and metabolites,and how they affect the development of lung cancer.Methods: The intestinal microbiota of 8 patients with early-stage lung cancer(ESLC),22 patients with non-early-stage lung cancer(NESLC)and15 healthy controls(HC)were sequenced by16 S r RNA gene sequencing technology.The serum metabolites of the participants were detected by liquid chromatography-mass spectrometry technology.The sequencing results of intestinal microorganisms and the detection results of metabolites were compared between groups by bioinformatics methods to find differential microorganisms,differential metabolites and the relationship between them.Results: The gut microbiota of 45 participants were analyzed and fou nd to be dysregulated in the gut microbiota of lung cancer patients.The ab undance of Enterobacteriaceae was higher in ESLC(15.01%),Enterobact eriaceae and Prevotellaceae in NESLC(10.55%,9.71%),and Prevotellac eae in HC(14.87%).At the genus level,apart from the similar higher abu ndance genus(Bacteroides),Faecalibacterium(10.71%),Prevotella＿9(12.56%),and Bacteroides(7.33%)were the most abundant genera identifie d in HC,Faecalibacterium(8.25%),Klebsiella(7.76%),and EscherichiaShigella(6.77%)in ESLC,Prevotella＿9(7.77%)and Escherichia-Shigell a(7.23%)in NESLC.When comparing the microbiota structure between l ung cancer patients and healthy controls,beta diversity showed difference s among the three groups(ADONIS,P = 0.016).Pathway enrichment anal ysis revealed that aminoacyl-t RNA biosynthesis pathway was enriched in HC vs ESLC,HC vs NESLC,and ESLC vs NESLC.This pathway was m ainly enriched with the metabolite L-valine,which was significantly corre lated with Lachnospira,Anaerostipes,Coprococcus＿3,Fusicatenibacter,Lachnospiraceae＿UCG-004,[Eubacterium]＿xylanophilum＿group,Lachn ospiraceae＿UCG-006,Burkholderia-Caballeronia-Paraburkholderia.Am ong them,Lachnospiraceae＿UCG-006 was the most correlated genus(cor relation = 0.49,P < 0.001),which was also a differential genus enriched i n HC.Conclusion: This study describes the characteristics of intestinal flora and serum metabolic profiles of patients with lung cancer at different stages.It reveals the relationship between lung cancer and L-valine,Lachnospiraceae＿UCG-006 and aminoacyl t RNA biosynthesis pathway,and proposes that L-valine is a potential marker for the diagnosis of lung cancer.