Intratumoral microbiota: A new force in diagnosing and treating pancreatic cancer

Jiang, Zhengting; Zhang, Wenjie; Zhang, Zhilin; Sha, Gengyu; Wang, Daorong; Tang, Dong

doi:10.1016/j.canlet.2022.216031

Cited by 16 publications

(8 citation statements)

References 80 publications

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“…In fact, the high degree of hypoxia in the tumor, immunosuppressive microenvironment, and disturbed vascular system are favorable conditions for rapid bacterial colonization, growth, and replication within the tumor. [35] Furthermore, we observed a marked discrepancy between the microbial composition of fecal samples and tumor samples from the same cohort of glioma patients. This implies that the gut microbiota is not the only possible source of intratumoral bacteria in glioma.…”

Section: Discussionmentioning

confidence: 81%

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Multi-omics analysis reveals novel interplays between intratumoral bacteria and glioma

Li,

Zhao,

Peng

et al. 2023

Preprint

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Emerging evidence highlights the potential impact of intratumoral microbiota on cancer. However, the microbial composition and function in glioma remains elusive. Consequently, our study aimed to investigate the microbial community composition in glioma tissues and elucidate its role in glioma development. We parallelly performed microbial profiling, transcriptome sequencing and metabolomics detection on tumor and adjacent normal brain tissues obtained from 50 glioma patients. We employed immunohistochemistry, multicolor immunofluorescence and FISH staining to observe the presence and location of bacteria. Furthermore, an animal model was employed to validate the impact of key bacteria on glioma development. Six genera were found to be significantly enriched in glioma tissues compared to its adjacent normal brain tissues, includingFusobacterium,Longibaculum,Intestinimonas,Pasteurella,LimosilactobacillusandArthrobacter. Both bacterial RNA and LPS were observed in glioma tissues. Multicolor immunofluorescence analysis showed higher bacterial LPS levels in tumor cells than in macrophages and in glioma tissue than in adjacent normal brain tissue. Integrated microbiomics, transcriptomics, and metabolomics revealed that genes associated with intratumoral microbes were enriched in multiple synapse-associated pathways and that metabolites associated with intratumoral microbes were (R)-N-methylsalsolinol, N-acetylaspartylglutamic acid, and N-acetyl-L-aspartic acid. Further mediation analysis suggested that intratumoral microbiome may affect the expression of neuron-related genes through bacteria-associated metabolites. In addition, a glioma mouse model suggested thatFusobacterium nucleatumpromoted glioma growth by increasing the levels of N-acetylneuraminic acid and the expression levels of CCL2, CXCL1, and CXCL2. In conclusion, our findings shed light on the intricate interplays between intratumoral bacteria and glioma.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Multi-omics analysis reveals novel interplays between intratumoral bacteria and glioma

Li,

Zhao,

Peng

et al. 2023

Preprint

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“…In terms of mechanisms, different metabolic regulators, such as lactic acid, phosphoinositide 3-kinase (PI3K), mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), c-Myc , hypoxia-inducible factor-1α (HIF-1α), p53, and peroxisome proliferator activated-receptors (PPARs), can prevent pancreatic cancer or improve its survival by regulating the metabolism of immune cells and pancreatic cancer cells [ 88 ]. Recently, accumulating evidences have found that the microbiome and its products can regulate the pancreatic tumor microenvironment, the biological behavior of pancreatic cancer cells, and the function of the immune system [ 89 ]. In addition, type I interferon α (IFNα) suppressed the viability and migration of human pancreatic cancer cell lines while affecting the toll-like receptor (TLR) signaling pathways in human pancreatic cancer cells.…”

Section: The Role Of Senescence In Types Of Pancreatic Diseasesmentioning

confidence: 99%

Changes in Pancreatic Senescence Mediate Pancreatic Diseases

Bian

Xiao

et al. 2023

IJMS

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In recent years, there has been a significant increase in age-related diseases due to the improvement in life expectancy worldwide. The pancreas undergoes various morphological and pathological changes with aging, such as pancreatic atrophy, fatty degeneration, fibrosis, inflammatory cell infiltration, and exocrine pancreatic metaplasia. Meanwhile, these may predispose the individuals to aging-related diseases, such as diabetes, dyspepsia, pancreatic ductal adenocarcinoma, and pancreatitis, as the endocrine and exocrine functions of the pancreas are significantly affected by aging. Pancreatic senescence is associated with various underlying factors including genetic damage, DNA methylation, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and inflammation. This paper reviews the alternations of morphologies and functions in the aging pancreas, especially β-cells, closely related to insulin secretion. Finally, we summarize the mechanisms of pancreatic senescence to provide potential targets for treating pancreatic aging-related diseases.

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“…ITM has emerged as a novel hotspot in microbiology and tumor research 2 . The relationship between cancer and microorganisms has been extensively explored, establishing microorganisms as vital biomarkers and modulators of cancer development and treatment 5 . ITM stimulate tumor cells and the immune microenvironment to produce a cancer‐promoting effect, possibly through the following pathways: (1) involvement in tumor cell DNA damage, 6 (2) the activation of oncogenic pathways, 7 (3) involvement in the tumor inflammatory response, 8 and (4) by influencing the tumor immune microenvironment 7 …”

Section: Introductionmentioning

confidence: 99%

The value of intratumoral microbiota in the diagnosis and prognosis of tumors

Zhou,

Zhang,

Fan

et al. 2024

Cell Biochemistry & Function

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Intratumoral microbiota (ITM) are microorganisms present in tumor cells. ITM participate in tumor development by affecting tumor cells directly and the tumor microenvironment (TME), indirectly. Alterations in ITM instigate changes in tumor DNA, activate oncogenic pathways, induce tumor inflammatory responses, disrupt normal immune activity, and facilitate the secretion of effectors leading to tumor progression, metastasis, or diminished therapeutic effects. ITM varies significantly in different types of cancer cells and disease states. The presence of certain ITM serves as a predictor of various disease states. Thus, ITM predicts tumorigenesis, tumor grade, treatment efficacy, and prognosis, making it a potential tumor biomarker. The present study aimed to determine the mechanisms by which ITM affects tumor development, especially through the TME; highlight the significant potential of ITM in enhancing tumor diagnosis and prognosis; and outline future directions for ITM research, with a focus on the development of innovative tumor markers.

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Intratumoral microbiota: A new force in diagnosing and treating pancreatic cancer

Cited by 16 publications

References 80 publications

Multi-omics analysis reveals novel interplays between intratumoral bacteria and glioma

Multi-omics analysis reveals novel interplays between intratumoral bacteria and glioma

Changes in Pancreatic Senescence Mediate Pancreatic Diseases

The value of intratumoral microbiota in the diagnosis and prognosis of tumors

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