Intratumoral bacteria interact with metabolites and genetic alterations in hepatocellular carcinoma

Xue, Chen; Jia, Junjun; Gu, Xinyu; Zhou, Lin; Lu, Juan; Zheng, Qiuxian; Su, Yuanshuai; Zheng, Shusen; Li, Lanjuan

doi:10.1038/s41392-022-01159-9

Cited by 19 publications

(30 citation statements)

References 5 publications

(6 reference statements)

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“…Compared with recent researches, 14–20 our study presents new findings and has potential translational value. On one hand, with a substantial sample size, we revealed the prognostic value of intratumoural microbiota in HCC.…”

Section: Discussionmentioning

confidence: 68%

“…revealed that patients with HCC possessed a dysbiotic microbiota that triggered hepatic stellate cell activation senescence, thereby promoting hepatocarcinogenesis 17 . Moreover, a multiomics investigation discovered that the intratumoural microbiome was closely related to metabolites and genetic alterations 18 . Despite these developments, the clinical significance of the intratumoural microbiome in HCC is still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Intratumoural microbiome can predict the prognosis of hepatocellular carcinoma after surgery

Sun

Guan

et al. 2023

Clinical & Translational Med

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Background The dismal prognosis of hepatocellular carcinoma (HCC) is closely associated with characteristics of the tumour microenvironment (TME). Recent studies have confirmed the presence and potential influence of the microbiome in TME on cancer progression. Elucidating the relationship between microbes in the TME and cancer could provide valuable insights into novel diagnostic markers and therapeutic strategies for HCC and thus warrants a closer investigation of the role of intratumoural microbiome in the HCC TME. Methods We determined the presence of intratumoural microbiome using fluorescence in situ hybridisation, and explored the microbial community profiles in the HCC TME in paired tumour and adjacent normal tissues using 16S rDNA sequencing. Microbial signatures were characterised in the paired group, and their correlation with clinical characteristics was further investigated. We clustered the microbial signatures of tumour tissues by hepatotypes, and further analysis was performed to elucidate the independent prognostic value of the hepatotypes. Results This study revealed that microbial profiles and community networks differed notably between tumours and adjacent normal tissues. Proteobacteria and Actinobacteria were the most abundant phyla in the HCC TME. The TME microbial profiles also revealed heterogeneities between individuals and between multiple tumour lesions. Clustering of the microbial profiles into two hepatotypes revealed different microbial network patterns. Additionally, the hepatotypes were revealed to be independent prognostic factors in patients with resected HCC. Conclusions Our study illuminates the microbial profiles in the TME of HCC and presents the hepatotype as a potential independent biomarker for the prognostic prediction of HCC after surgery.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Intratumoural microbiome can predict the prognosis of hepatocellular carcinoma after surgery

Sun

Guan

et al. 2023

Clinical & Translational Med

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“…In a previous study, we found that the metabolic patterns (such as abnormal tryptophan metabolism) of HCC tissues were distinct from those of adjacent nontumor tissues. [ 12 ] Here, we performed LC–MS to explore the different metabolites between 15 pairs of tumor tissues and adjacent nontumor tissues of HCC patients. It revealed that the level of the Kyn derivative 3‐HAA was lower in tumor tissues than in adjacent nontumor tissues, and the time‐dependent receiver operating characteristic (ROC) analyses for the survival prediction of 3‐HAA yielded the area under the curve of 0.951 (Figure 1B ), suggesting that the level of 3‐HAA could be associated with the development of HCC.…”

Section: Resultsmentioning

confidence: 99%

Effects of 3‐HAA on HCC by Regulating the Heterogeneous Macrophages—A scRNA‐Seq Analysis

Xue

Zheng

et al. 2023

Advanced Science

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Kynurenine derivative 3-hydroxyanthranilic acid (3-HAA) is known to regulate the immune system and exhibit anti-inflammatory activity by inhibiting T-cell cytokine secretion and influencing macrophage activity. However, the definite role of 3-HAA in the immunomodulation of hepatocellular carcinoma (HCC) is largely unexplored. An orthotopic HCC model and treated with 3-HAA by intraperitoneal injection is developed. Furthermore, cytometry by time-of-flight (CyTOF) and single-cell RNA sequencing (scRNA-seq) analyses are carried out to define the immune landscape of HCC. It is found that 3-HAA treatment can significantly suppress tumor growth in the HCC model and alter the level of various cytokines in plasma. CyTOF data shows that 3-HAA significantly increases the percentage of F4/80 hi CX3CR1 lo Ki67 lo MHCII hi macrophages and decreases the percentage of F4/80 lo CD64 + PD-L1 lo macrophages. scRNA-seq analyses demonstrate that 3-HAA treatment is proved to regulate the function of M1 macrophages, M2 macrophages, and proliferating macrophages. Notably, 3-HAA inhibits the proinflammatory factors TNF and IL-6 in multiple cell subsets, including resident macrophages, proliferating macrophages, and pDCs. This study reveals the landscape of immune cell subsets in HCC in response to 3-HAA, indicating that 3-HAA may be a promising therapeutic target for HCC.

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“…Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, greatly threatens human health greatly by its striking morbidity and mortality (161). Compared with adjacent normal tissue, increased m6A modification was found in the YAP 3′ UTR region of HCC tissue.…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

Emerging role of interaction between m6A and main ncRNAs in gastrointestinal (GI) cancers

Yu²,

Guo³

et al. 2023

Front. Immunol.

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As a prevalent epigenetic modification, the role of m6A has been increasingly highlighted in the alteration of numerous RNAs implicated with multiple biological processes, such as formation, export, translation, and degradation. With further the understanding of m6A, accumulating evidence shows that m6A modification similarly affects metabolic process of non-coding genes. But the specifical interplay of m6A and ncRNAs (non-coding RNAs) in gastrointestinal cancers still lacks complete discussion. Thus, we analyzed and summarized how ncRNAs affect the regulators of m6A and by what means the expression of ncRNAs is altered via m6A in gastrointestinal cancers. We focused on the effect of the interaction of m6A and ncRNAs on the molecular mechanisms of malignant behavior in gastrointestinal cancers, revealing more possibilities of ncRNAs for diagnosis and treatment in term of epigenetic modification.

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Intratumoral bacteria interact with metabolites and genetic alterations in hepatocellular carcinoma

Cited by 19 publications

References 5 publications

Intratumoural microbiome can predict the prognosis of hepatocellular carcinoma after surgery

Intratumoural microbiome can predict the prognosis of hepatocellular carcinoma after surgery

Effects of 3‐HAA on HCC by Regulating the Heterogeneous Macrophages—A scRNA‐Seq Analysis

Emerging role of interaction between m6A and main ncRNAs in gastrointestinal (GI) cancers

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