J Liver Cancer.  2020 Mar;20(1):32-40. 10.17998/jlc.20.1.32.

Gut-microbiome Taxonomic Profiling as Non-invasive Biomarkers for the Early Detection of Alcoholic Hepatocellular Carcinoma

• Seok J
• Suk KT

• KMID: 2505840
• DOI: http://doi.org/10.17998/jlc.20.1.32

Abstract

Background/Aims
Hepatocellular carcinoma (HCC) is a prevalent form of primary liver cancer and the fifth leading cause of worldwide cancer mortality. Though early diagnosis of HCC is important, so far lack of effective biomarkers for early diagnosis of HCC has been a problem. In this study, we searched for potential functional biomarkers of alcoholic HCC by using metagenomics approach.
Methods
Between September 2017 and April 2019, normal control (n=44), alcoholic liver cirrhosis (n=44), and alcoholic HCC (n=13) groups were prospectively enrolled and analyzed. Gut microbiota was analyzed using the 16S-based microbiome taxonomic profiling platform of EzBioCloud Apps and analyzing system.
Results
There was a statistically significant difference among groups in diversity (P<0.05). In the comparison of phylum between cirrhosis and HCC, Proteobacteria were increased and Bacteroidetes were decreased. Firmicutes were not significantly different among the three groups. In the taxonomic profiling, relative abundance of Lactobacillus in the cirrhosis and HCC groups showed richness (P<0.05). In the biomarker analysis between cirrhosis and HCC, obiquinome Fe-S protein 3, global nitrogen regulator, Vesicle-associated membrane protein 7, toxin YoeB, peroxisome-assembly ATPase, and nitrogen oxide reductase regulator were differently expressed (P<0.001).
Conclusions
Alcoholic HCC showed different expressions in the stool taxonomy and biomarker compared with that of cirrhosis and control. Therefore, new biomarkers using stool analysis for alcoholic HCC are necessary.

Keyword

Hepatocellular carcinoma; Biomarker; Taxonomy; Microbiome

Figure

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  Figure 1. Alpha diversity in the normal control, alcoholic liver cirrhosis, and alcoholic hepatocellular carcinoma (HCC) groups. Alcoholic liver cirrhosis and alcoholic HCC groups showed decrease alpha diversity compared to that of the normal control group. ACE, Abundance-based Coverage Estimator; OTU, operational taxonomic unit; MTP, microbial taxonomic profiling. *P<0.001.

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  Figure 2. Beta diversity in the normal control, alcoholic liver cirrhosis, and alcoholic hepatocellular carcinoma (HCC) groups. Alcoholic liver cirrhosis and alcoholic HCC groups had similar beta diversity and showed different patterns compared with that of the normal control group.

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  Figure 3. Phylum level averaged taxonomic compositions of the microbial taxonomic profiling sets. HCC, hepatocellular carcinoma.

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  Figure 4. Lactobacillus taxonomic relative abundance in the normal control, alcoholic liver cirrhosis, and alcoholic hepatocellular carcinoma (HCC) groups. Alcoholic liver cirrhosis and alcoholic HCC groups showed increased Lactobacillus compared to that in the normal control group. * P<0.05; † P<0.001.

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  Figure 5. Firmicutes to Bacteroidetes ratio in the normal control, alcoholic liver cirrhosis, and alcoholic hepatocellular carcinoma groups. F/B, Firmicutes/Bacteroidetes.

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