BACKGROUND Hepatocellular carcinoma(HCC),the predominant form of primary liver cancer,is a key contributor to cancer-related deaths globally.However,HCC diagnosis solely based on blood biochemical markers lacks both s...BACKGROUND Hepatocellular carcinoma(HCC),the predominant form of primary liver cancer,is a key contributor to cancer-related deaths globally.However,HCC diagnosis solely based on blood biochemical markers lacks both sensitivity and specificity.AIM To investigate alterations of the fecal metabolome and intestinal bacteria and reveal the correlations among differential metabolites,distinct bacteria,and serum indicators.METHODS To uncover potentially effective therapeutic targets for HCC,we utilized nontargeted liquid chromatography-mass spectrometry and high-throughput DNA sequencing targeting the 16S rRNA gene.This comprehensive approach allowed us to investigate the metabolome and microbial community structure of feces samples obtained from patients with HCC.Furthermore,we conducted an analysis to assess the interplay between the fecal metabolome and intestinal bacterial population.RESULTS In comparison to healthy controls,a notable overlap of 161 differential metabolites and 3 enriched Kyoto Encyclopedia of Genes and Genomes pathways was observed in the HCC12(comprising patients with stage I and II HCC)and HCC34 groups(comprising patients with stage III and IV HCC).Lachnospira,Streptococcus,and Veillonella had significant differences in abundance in patients with HCC.Notably,Streptococcus and Veillonella exhibited significant correlations with serum indicators such as alpha-fetoprotein(AFP).Meanwhile,several differential metabolites[e.g.,4-keto-2-undecylpyrroline,dihydrojasmonic acid,1,8-heptadecadiene-4,6-diyne-3,10-diol,9(S)-HOTrE]also exhibited significant correlations with serum indicators such asγ-glutamyl transferase,total bilirubin,AFP,aspartate aminotransferase,and albumin.Additionally,these two genera also had significant associations with differential metabolites such as 1,2-Dipentadecanoyl-rac-glycerol(15:0/20:0/0:0),arachidoyl ethanolamide,and 4-keto-2-undecylpyrroline.CONCLUSION Our results suggest that the metabolome of fecal samples and the composition of intestinal bacteria hold promise as potential biomarkers for HCC diagnosis.展开更多
基金Supported by the Department of Science and Technology of Shanxi Province,No.20210302124369the Health Commission of Shanxi Province,No.2021116Shanxi Administration of Traditional Chinese Medicine,No.2024ZYY2C054.
文摘BACKGROUND Hepatocellular carcinoma(HCC),the predominant form of primary liver cancer,is a key contributor to cancer-related deaths globally.However,HCC diagnosis solely based on blood biochemical markers lacks both sensitivity and specificity.AIM To investigate alterations of the fecal metabolome and intestinal bacteria and reveal the correlations among differential metabolites,distinct bacteria,and serum indicators.METHODS To uncover potentially effective therapeutic targets for HCC,we utilized nontargeted liquid chromatography-mass spectrometry and high-throughput DNA sequencing targeting the 16S rRNA gene.This comprehensive approach allowed us to investigate the metabolome and microbial community structure of feces samples obtained from patients with HCC.Furthermore,we conducted an analysis to assess the interplay between the fecal metabolome and intestinal bacterial population.RESULTS In comparison to healthy controls,a notable overlap of 161 differential metabolites and 3 enriched Kyoto Encyclopedia of Genes and Genomes pathways was observed in the HCC12(comprising patients with stage I and II HCC)and HCC34 groups(comprising patients with stage III and IV HCC).Lachnospira,Streptococcus,and Veillonella had significant differences in abundance in patients with HCC.Notably,Streptococcus and Veillonella exhibited significant correlations with serum indicators such as alpha-fetoprotein(AFP).Meanwhile,several differential metabolites[e.g.,4-keto-2-undecylpyrroline,dihydrojasmonic acid,1,8-heptadecadiene-4,6-diyne-3,10-diol,9(S)-HOTrE]also exhibited significant correlations with serum indicators such asγ-glutamyl transferase,total bilirubin,AFP,aspartate aminotransferase,and albumin.Additionally,these two genera also had significant associations with differential metabolites such as 1,2-Dipentadecanoyl-rac-glycerol(15:0/20:0/0:0),arachidoyl ethanolamide,and 4-keto-2-undecylpyrroline.CONCLUSION Our results suggest that the metabolome of fecal samples and the composition of intestinal bacteria hold promise as potential biomarkers for HCC diagnosis.
