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

• Published in: Scientific reports Vol. 11; no. 1; p. 7870
• Main Authors: Neuzillet, Cindy, Marchais, Manon, Vacher, Sophie, Hilmi, Marc, Schnitzler, Anne, Meseure, Didier, Leclere, Renaud, Lecerf, Charlotte, Dubot, Coraline, Jeannot, Emmanuelle, Klijanienko, Jerzy, Mariani, Odette, Calugaru, Valentin, Hoffmann, Caroline, Lesnik, Maria, Badois, Nathalie, Borcoman, Edith, Piaggio, Eliane, Kamal, Maud, Le Tourneau, Christophe, Bieche, Ivan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.04.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/1536; 631/67/1665; 631/67/1857; 631/67/327; 631/67/580; Bacteria; CD163 antigen; Drinking behavior; Fusobacterium nucleatum; Gene expression; Gram-negative bacteria; Head & neck cancer; Humanities and Social Sciences; Immunohistochemistry; Life Sciences; Lipopolysaccharides; Lymph nodes; Macrophages; Medical prognosis; Metastases; Microbiomes; Microenvironments; multidisciplinary; Multivariate analysis; Oral cancer; Oral squamous cell carcinoma; rRNA 16S; Science; Science (multidisciplinary); Sensitivity analysis; Squamous cell carcinoma; Tobacco; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-86816-9

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.