High‐risk Stage III colon cancer patients identified by a novel five‐gene mutational signature are characterized by upregulation of IL‐23A and gut bacterial translocation of the tumor microenvironment

Ge, Weiting; Hu, Hanguang; Cui, Wen; Xu, Junqiang; Hu, Wangxiong; Weng, Xingyue; Xin, Qin; Huang, Yanqin; Han, Weidong; Hu, Yeting; Yu, Jian; Zhang, Wufeng; Ye, Sisi; Qi, Ling; Huang, Pingjie; Chen, Lirong; Ding, Kefeng; Wang, Li Dong; Zheng, Shu

doi:10.1002/ijc.32775

Cited by 39 publications

(38 citation statements)

References 41 publications

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“…Some of the tumour genera of (possible) oral origin identi ed in our study, were associated with tumour mucosa previously, namely Fusobacterium, Campylobacter, Leptotrichia, Parvimonas, Gemella, Granulicatella, Eikenella, Selenomonas, Neisseria, Streptococcus, Alloprevotella, Veilonella, Haemophilus [8,31,32,[61][62][63][64][65][66][67][68]. In contrast, Solobacterium was reported increased [31], while Slackia and Pseudomonas were shown to be decreased [12,19] in fecal samples of CRC patients compared to healthy donors, and, in one epidemiological study, the presence of Treponema in the oral cavity was associated with increased risk of CRC [29], but none of these were previously associated with tumour mucosa.…”

Section: Tumour Crc Microbial Subtypessupporting

confidence: 57%

Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

Zwinsová¹,

Петров²,

Hrivňáková³

et al. 2020

Preprint

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BackgroundLong-term dysbiosis of the gut microbiome has a significant impact on the development, progression and the aggressiveness of colorectal cancer (CRC) and may explain part of the observed heterogeneity of the disease from phenotypic, prognostic and response to treatment perspectives. Although the shifts in gut microbiome in the normal-adenoma-carcinoma sequence have been described, the landscape of microbiome within CRC and its associations with clinical variables remain under-explored. ResultsWe performed 16S rRNA gene sequencing of paired tumour tissue, adjacent visually-normal mucosa and stool swabs of N=186 patients with stage 0-IV CRC to describe the tumour microbiome and its association with clinical variable and to derive tumour microbial subtypes.We identified new genera never previously associated with CRC tumour mucosa (Flavonifractor, Haemophilus, Howardella, Pseudomonas, Sutterella, Treponema 2) or CRC (Actinobacillus, Aggregatibacter, Bergeyella, Phocaeiola, Defluviitaleaceae UCG-011, Massilia, Tyzzerella 4). The bacteria residing on tumour-mucosa were dominated by genera belonging to (potential) oral pathogens. Based on tumour microbial profiles, we stratified CRC patients into three subtypes. The subtypes were significantly associated with prognostic factors such as tumor grade, primary tumour sidedness and TNM staging, with one subtype enriched in tumours with poor prognosis. Further, we inspected the associations of microbiome with clinical variables in a subtype-agnostic setting. The primary tumour-associated clinical variables predominantly correlated with tumour mucosal microbiome, while the presence of local and distant metastases was mostly associated with the stool microbiome.ConclusionsUnderstanding the interactions of the bacteria residing on tumour mucosa within different CRC tumour microbiome subtypes will help to better understand the underlying biological background of the heterogeneity of this disease. Indeed, the tumour microbiome is a possible source of additional integrative markers of CRC patients’ survival and prognosis. We found that CRC microbiome is strongly correlated with clinical variables, but these associations are dependent on the microbial environment (tumour mucosa, normal mucosa, stool). Our study thus identifies limitations of the usage of microbiome composition as marker of CRC progression, suggesting the need of combining several sampling sites (e.g. stool and tumour swabs).

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Section: Tumour Crc Microbial Subtypessupporting

confidence: 57%

Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

Zwinsová¹,

Петров²,

Hrivňáková³

et al. 2020

Preprint

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“…Moreover, P. micra may contribute to the pathogenesis of periodontitis by stimulating Toll-like receptor 4, nucleotide binding oligomerization domain containing (NOD)1 and NOD2 (54). It has also been reported that P. micra may be involved in gut bacterial translocation and the upregulation of interleukins in the tumor microenvironment (55). A previous study demonstrated that APC Min/+ mice gavaged with P. micra exhibited a significantly higher tumor burden and tumor load, and cell proliferation was significantly higher in the colon tissues of P. micra gavaged germ-free mice compared with control mice (56).…”

Section: Discussionmentioning

confidence: 99%

Alteration of the abundance of <em>Parvimonas micra</em> in the gut along the adenoma‑carcinoma sequence

Yang²,

Wang³

et al. 2020

Oncol Lett

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Parvimonas micra (P. micra) is reported to be associated with colorectal cancer (CRC). However, its association with colorectal adenoma (CRA) and its role in the initiation of colorectal tumors remain unknown. The present study aimed to clarify the relationship between P. micra and CRA and CRC by exploring the changes of P. micra abundance in an adenoma-carcinoma sequence in a new cohort and 4 public sequencing datasets. To investigate the alterations of P. micra abundance in the gut along the adenoma-carcinoma sequence, quantitative PCR (qPCR) was conducted to measure the relative abundance of P. micra in fecal samples from 277 subjects (128 patients with CRA, 66 patients with CRC and 83 healthy individuals, as controls) who underwent colonoscopy as outpatients. Then, the relative abundance of P. micra was analyzed in fecal samples from 596 subjects (185 healthy controls, 158 CRC, 253 CRA) in four public 16S rRNA sequencing datasets. The qPCR results demonstrated that the CRA group had an abundance of P. micra (P=0.2) similar to that of the healthy control group, while the CRC group had a significantly increased abundance (P=8.2x10-11). The level of P. micra effectively discriminated patients with CRC from healthy controls, while it poorly discriminated patients with CRA from healthy controls; with an area under the receiver operating characteristic curve of 0.867 for patients with CRC and 0.554 for patients with CRA. The same pattern of the alteration of P. micra abundance, which was low in healthy controls and patients with CRA but elevated in patients with CRC, was found in all four public sequencing datasets. These results suggested that P. micra was closely associated with, and may serve as a diagnostic marker for, CRC but not CRA. Moreover, it was indicated that P. micra may be an opportunistic pathogen of CRC, which may promote CRC development but serve a limited role in tumorigenesis.

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“…Furthermore, the integrated analysis of 16s rRNA and metabolomics data showed that there were 19 functional relationship pairs, including eight altered microbiota (e.g., Ruminiclostridium and Prevotellaceae_UCG_001) and 16 disturbed metabolites (e.g., C10H11NO3 and C21H32O8) between the JK5G and model groups. Actually, Alloprevotella has been regarded as the cancer-related bacteria in colon cancer or visceral leishmaniasis (30,31). Moreover, a previous study showed that the abundance of the Ruminiclostridium genus was related to the enhancement of animal immune responses to spore adsorbent antigen and probiotics (32).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effect of a Microecological Preparation on Azoxymethane/Dextran Sodium Sulfate-Induced Inflammatory Colorectal Cancer in Mice

Zhang

Chen

et al. 2020

Front. Oncol.

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This study aims to investigate the antitumor effect and the possible mechanism of a microecological preparation (JK5G) in mice. The mice treated with AOM/DSS were then randomly divided into the two model groups and the JK5G group, and the blank control group was included. Fecal samples were used for liquid chromatographymass spectrometry and 16S rRNA gene sequencing analyses to reveal metabolic perturbations and gut flora disorders to demonstrate the effects of JK5G. Compared with the mice in the control group, the weight and food intake of mice after JK5G treatment were both upregulated. Moreover, JK5G could inhibit the growth of colon tumors and prolong the survival rate of mice, as well as inhibit the levels of cytokines in serum. The proportions of lymphocytes, T cells, CD3 + CD4 + T cells, and CD3 + CD8 + T cells in the spleen of the JK5G mice were all significantly increased compared to those in the control group (p < 0.05). Similarly, compared with the model group, the proportions of lymphocytes, B cells, T cells, natural killer T cells, CD3 + CD4 + T cells, and CD3 + CD8 + T cells in the intestinal tumors of the JK5G mice were significantly increased (p < 0.05). Furthermore, 16S rRNA high-throughput sequencing data revealed that Alloprevotella in the JK5G group was significantly upregulated, and Ruminiclostridium, Prevotellaceae_UCG_001, and Acetitomaculum were significantly downregulated. Fecal and serum metabolite analysis detected 939 metabolites, such as sildenafil and pyridoxamine, as well as 20 metabolites, including N-Palmitoyl tyrosine and dihydroergotamine, which were differentially expressed between the JK5G and model groups. Integrated analysis of 16s rRNA and metabolomics data showed that there were 19 functional relationship pairs, including 8 altered microbiota, such as Ruminiclostridium and Prevotellaceae_UCG_001, and 16 disturbed metabolites between the JK5G and model groups. This study revealed that JK5G treatment

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High‐risk Stage III colon cancer patients identified by a novel five‐gene mutational signature are characterized by upregulation of IL‐23A and gut bacterial translocation of the tumor microenvironment

Cited by 39 publications

References 41 publications

Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

Alteration of the abundance of <em>Parvimonas micra</em> in the gut along the adenoma‑carcinoma sequence

Inhibitory Effect of a Microecological Preparation on Azoxymethane/Dextran Sodium Sulfate-Induced Inflammatory Colorectal Cancer in Mice

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High‐risk Stage III colon cancer patients identified by a novel five‐gene mutational signature are characterized by upregulation of IL‐23A and gut bacterial translocation of the tumor microenvironment

Cited by 39 publications

References 41 publications

Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

Alteration of the abundance of <em>Parvimonas&nbsp;micra</em> in the gut along the adenoma‑carcinoma sequence

Inhibitory Effect of a Microecological Preparation on Azoxymethane/Dextran Sodium Sulfate-Induced Inflammatory Colorectal Cancer in Mice

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Alteration of the abundance of <em>Parvimonas micra</em> in the gut along the adenoma‑carcinoma sequence