The landscape of bacterial presence in tumor and adjacent normal tissue across 9 major cancer types using TCGA exome sequencing

Rodriguez, Rebecca M.; Hernandez, Brenda Y.; Menor, Mark; Deng, Youping; Khadka, Vedbar S.

doi:10.1016/j.csbj.2020.03.003

Cited by 39 publications

(53 citation statements)

References 41 publications

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“…Periodontal pathogens including Fusobacterium nucleatum ( F. nucleatum ) are a risk factor for OSCC, independent from tobacco, alcohol, and HPV 11 , 13 , and their abundance in saliva samples increases with tumor progression 14 , 15 . Little is known about the association between intratumoral F. nucleatum and HNSCC tumor biology 16 , 17 . Moreover, F. nucleatum has been reported to modulate local immunity in other cancers (mainly, colorectal cancers), particularly macrophages and T regulatory cells (Tregs), via Toll like receptor (TLR) 2–4 signaling 18 – 20 .…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients

Neuzillet

Marchais

Vacher

et al. 2021

Sci Rep

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Changes in the oral microbiome, particularly Fusobacterium nucleatum, are associated with oral squamous cell carcinoma (OSCC). F. nucleatum has been reported to modulate local immunity in cancers. We aimed to assess the association between intratumoral F. nucleatum and clinico-pathological features, relapse, and overall survival (OS) in two independent cohorts of patients with OSCC, and to explore the interplay with immune-related genes. We retrospectively analyzed tissue samples from a first cohort of 122 patients with head and neck squamous cell carcinoma, including 61 OSCC (cohort #1), and a second cohort of 90 additional OSCC (cohort #2). We then performed a sensitivity analysis on the merged cohort of OSCC patients (N = 151). F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. The presence of gram-negative bacteria and macrophages was confirmed by LPS and CD163 immunostainings, respectively. F. nucleatum positivity was associated with older age, less alcohol and combined alcohol plus tobacco consumption, and less frequent lymph node invasion. There was a trend for a lower recurrence rate in F. nucleatum-positive cases, with less metastatic relapses compared to F. nucleatum-negative tumors, and significantly longer OS, relapse-free and metastasis-free survival. F. nucleatum status was independently associated with OS in multivariate analysis. Immune-related gene and immunohistochemistry analyses showed that gram-negative bacteria load inversely correlated with M2 macrophages. F. nucleatum-associated OSCC has a specific immune microenvironment, is more frequent in older, non-drinking patients, and associated with a favorable prognosis.

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Section: Introductionmentioning

confidence: 99%

Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients

Neuzillet

Marchais

Vacher

et al. 2021

Sci Rep

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“…Further, the output from these workflows combined with phylogenetic and protein-functional predictions from bioinformatics pipelines such as PICRUSt, Tax4Fun, and ShortBRED, among others, provide important clues in the understanding of microbial differences and commonalities and the potential impact on differential outcomes, therapeutic response, and population inter-variability. Recent works [ 84 – 86 ] demonstrate the utility of tissue-associated microbial detection derived from existing human sequencing data and the computational tools to characterize them. Differences may highlight effectors that impact the treatment decision making process and potential for targeted therapies.…”

Section: Resultsmentioning

confidence: 99%

Tissue-associated microbial detection in cancer using human sequencing data

et al. 2020

Self Cite

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Cancer is one of the leading causes of morbidity and mortality in the globe. Microbiological infections account for up to 20% of the total global cancer burden. The human microbiota within each organ system is distinct, and their compositional variation and interactions with the human host have been known to attribute detrimental and beneficial effects on tumor progression. With the advent of next generation sequencing (NGS) technologies, data generated from NGS is being used for pathogen detection in cancer. Numerous bioinformatics computational frameworks have been developed to study viral information from host-sequencing data and can be adapted to bacterial studies. This review highlights existing popular computational frameworks that utilize NGS data as input to decipher microbial composition, which output can predict functional compositional differences with clinically relevant applicability in the development of treatment and prevention strategies.

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“…Bacterial, archaea, and viral transcripts’ (BAVT) expression is found in RNA-seq experiments of samples from normal tissues and cancers [ 11 , 32 , 33 , 34 ]. Most of the metagenomic and metatranscriptomics studies are focused on cancers from the gastrointestinal tract [ 35 ], or skin [ 36 ], or head/neck regions [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Most of the metagenomic and metatranscriptomics studies are focused on cancers from the gastrointestinal tract [ 35 ], or skin [ 36 ], or head/neck regions [ 37 ]. However, the presence of microorganisms and BAVT in the female upper genital tract has recently been reported [ 11 , 12 , 34 ]. These studies not only have demonstrated the existence of microorganism in the female genital tract, but also have observed that components of this ecosystem gradually change from the vagina to the peritoneal fluid [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Bacterial, Archaea, and Viral Transcripts (BAVT) Expression in Gynecological Cancers and Correlation with Regulatory Regions of the Genome

Bosquet

Pedra-Nobre

Devor

et al. 2021

Cancers

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Bacteria, archaea, and viruses are associated with numerous human cancers. To date, microbiome variations in transcription have not been evaluated relative to upper female genital tract cancer risk. Our aim was to assess differences in bacterial, archaea, and viral transcript (BAVT) expression between different gynecological cancers and normal fallopian tubes. In this case-control study we performed RNA sequencing on 12 normal tubes, 112 serous ovarian cancers (HGSC) and 62 endometrioid endometrial cancers (EEC). We used the centrifuge algorithm to classify resultant transcripts into four indexes: bacterial, archaea, viral, and human genomes. We then compared BAVT expression from normal samples, HGSC and EEC. T-test was used for univariate comparisons (correcting for multiple comparison) and lasso for multivariate modelling. For validation we performed DNA sequencing of normal tubes in comparison to HGSC and EEC BAVTs in the TCGA database. Pathway analyses were carried out to evaluate the function of significant BAVTs. Our results show that BAVT expression levels vary between different gynecological cancers. Finally, we mapped some of these BAVTs to the human genome. Numerous map locations were close to regulatory genes and long non-coding RNAs based on the pathway enrichment analysis. BAVTs may affect gynecological cancer risk and may be part of potential targets for cancer therapy.

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The landscape of bacterial presence in tumor and adjacent normal tissue across 9 major cancer types using TCGA exome sequencing

Cited by 39 publications

References 41 publications

Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients

Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients

Tissue-associated microbial detection in cancer using human sequencing data

Bacterial, Archaea, and Viral Transcripts (BAVT) Expression in Gynecological Cancers and Correlation with Regulatory Regions of the Genome

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