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

ABSTRACT: 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.

SUBMITTER: Neuzillet C

PROVIDER: S-EPMC8041800 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOral squamous cell carcinoma (OSCC) is the most common type of oral cancer, which remains a major cause of morbidity and mortality in patients with head and neck cancers. However, the critical immune-related signatures and their prognostic values have rarely been investigated.Materials and methodsGene differential analysis was used to measure the differences of gene expression between the groups. Correlation analysis was used to assess the association between the gene expression levels and immune-related risk score/DNA methylation levels. The gene set enrichment analysis (GSEA) was used to identify the pathways or cell types enriched by those identified differentially expressed genes (DEGs).ResultsIn this study, we identified four immune-related gene signatures, including CTSG, TNFRSF4, LCORL, and PLAU, that were significantly associated with the overall survival in OSCC patients from the Cancer Genome Atlas (TCGA) OSCC cohort. Moreover, these four immune-related signatures were differentially expressed between the OSCC and nontumor tissues. The two groups (high and low risk) stratified by the immune-related risk scores had significantly different OS and mortality rates. The gene expression patterns and prognostic values of these immune-related signatures were also verified in two independent validation cohorts. Furthermore, the downregulated genes in the high-risk group (which were also upregulated in the low-risk group) were significantly enriched in the cell type-specific signatures of type 2 T helper cell (Th2), plasmacytoid dendritic cell (pDC), and memory B cell. In contrast, the upregulated genes in the high-score group were enriched in growth factor receptor-related signaling pathways, such as the VEGFA-VEGFR2 signaling pathway, PI3K-Akt signaling pathway, focal adhesion-PI3K-Akt-mTOR signaling pathway, and PDGF pathway, suggesting that those pathways were inversely correlated with immune cell infiltration.ConclusionIn summary, the immune-related signatures had the potential for predicting the risk of OSCC patients. Moreover, the present study also improved our understanding of the association between the growth factor receptor pathways and immune cell infiltration in OSCC.

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

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