【STTT】Li Lanjuan/Zheng Shusen of Zhejiang University reveals the interaction of bacteria with metabolites and genetic alterations in hepatocellular carcinoma tumors

This article is the original of the translational medicine network, please indicate the source when reprinting

Author: Mia

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, with most patients diagnosed with advanced cancer
when treatment is largely ineffective.
Therefore, early diagnosis is urgently needed to improve the prognosis of patients with HCC
.

On September 28, the team of Li Lanjuan and Zheng Shusen of Zhejiang University published a research paper entitled "Intratumoral bacteria interact with metabolites and genetic alterations in hepatocellular carcinoma" online on Signal Transduction and Targeted Therapy
。 The study revealed that the tumor microbiota is closely related
to changes in host metabolism, epigenetics, and gene expression profile.

background

 01 

Although many tumors have intratumoral bacteria, the characteristics of the tumor microbiome are difficult to analyze
due to limited detection techniques.
Recently, Nejman et al.
found that different tumor types have different microbiotas, and bacterial metabolism is closely related to
clinical features.
They identified cancer-type-specific microbial signatures
of the microbiome from seven tumors.
In the Cancer Genome Atlas, unique microbial reads and tags were found in tissues and blood within and between the major cancer types of 33 cancers, suggesting that the cancer microbiome may provide new information
for cancer diagnosis.

While better sequencing techniques have identified the intra-tumor microbiome as an important component of the tumor microenvironment, the characteristics of microbes, metabolites, and potential gene regulatory networks in HCC are unclear
.

Research overview

 02 

To study the microbiome, the researchers analyzed 47 pairs of HCC tissues and normal control liver tissue
in the First Affiliated Hospital of Zhejiang University School of Medicine.
The researchers found that there were differences in the microbial population structure of HCC tissues at the phyla, family and genus levels, and control tissues, and that their overall microbial composition deviated significantly from normal liver tissue
.

The iconic microbial environment of HCC patients suggests that changes in metabolites may be influenced by the tumor microbiota
.
The researchers identified different metabolites using liquid chromatography-mass spectrometry (LC-MS) and found that the metabolic patterns of HCC tissue were different
compared to normal liver tissue.

As there is growing evidence that the microbiome influences host epigenetic regulation, the researchers analyzed the effects
of DNA methylation on differential gene expression by measuring the transcriptome and epigenomes of five pairs of HCC tumors and normal liver tissue.
RNA-seq showed that 737 transcripts in HCC tissue were significantly downregulated and 1004 were upregulated
.
Genoset enrichment analysis (GSEA) of differentially expressed genes (DEGs) showed that highly expressed genes were mainly enriched
in cell cycles, cell cycle processes, nuclear chromosomes, protein-DNA complexes and similar pathways.

To further understand the function of DEGs, the researchers built a protein-protein interaction network using the STRING database, identifying DNA methylation profiles
of five pairs of HCC tissues and normal liver tissue.
They found that the methylation patterns of these DEGs differed between HCC and normal tissues
.
Methylation of different regions of the genome leads to different regulatory mechanisms of
gene expression.
Therefore, the researchers used clustering analysis to determine the distribution of differential methylated cytosine (DMC) in the genome, analyzing
the first 500 significantly different methylation sites.
The analysis showed that increased DNA methylation of CpG islands within the gene promoter region inhibited transcriptional initiation, thereby silencing
these genes.
Conversely, decreased DNA methylation in the promoter region leads to increased
expression of the target gene.

Through Spearman-related analysis, the researchers found that some microorganisms, such as Halomonas, were significantly positively associated with certain metabolites and negatively correlated
with lL-arginine, O-phosphate ethanolamine, acetaminophen, and rosmarinic acid.
In addition, the researchers analyzed the interaction between the microbiome and the host transcriptome and found that 10 metabome-related microbial populations were closely related to 25 methylation-related
DEGs.

Research summary

 03 

In summary, the microbiome, metabolome, host transcriptome, and DNA methylation of HCC tissues and paired normal tissues show several intratumoral microbial signatures
.
In addition, correlations between microbial species and metabolites, DNA methylation and genetic alteration, and microbial species and genetic alterations may contribute
to a better understanding of the tumor microenvironment.
Microbes closely related to tumorigenesis and progression may become new biomarkers in the diagnosis and prognosis
of HCC patients.
However, further validation of the presence of bacteria in HCC tumors and their effects on
tumor cell phenotypes is also needed.

Resources:

This article is intended to introduce medical research advances and cannot be used as a reference for
treatment options.
For health guidance, please visit a regular hospital
.

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