The oral cancer microbiome contains tumor space–specific and clinicopathology-specific bacteria

Abstract

The crosstalk between the oral microbiome and oral cancer has yet to be characterized. This study recruited 218 patients for clinicopathological data analysis. Multiple types of specimens were collected from 27 patients for 16S rRNA gene sequencing, including 26 saliva, 16 swabs from the surface of tumor tissues, 16 adjacent normal tissues, 22 tumor outer tissue, 22 tumor inner tissues, and 10 lymph nodes. Clinicopathological data showed that the pathogenic bacteria could be frequently detected in the oral cavity of oral cancer patients, which was positively related to diabetes, later T stage of the tumor, and the presence of cervical lymphatic metastasis. Sequencing data revealed that compared with adjacent normal tissues, the microbiome of outer tumor tissues had a greater alpha diversity, with a larger proportion of Fusobacterium, Prevotella, and Porphyromonas, while a smaller proportion of Streptococcus. The space-specific microbiome, comparing outer tumor tissues with inner tumor tissues, suggested minor differences in diversity. However, Fusobacterium, Neisseria, Porphyromonas, and Alloprevotella were more abundant in outer tumor tissues, while Prevotella, Selenomonas, and Parvimonas were enriched in inner tumor tissues. Clinicopathology-specific microbiome analysis found that the diversity was markedly different between negative and positive extranodal extensions, whereas the diversity between different T-stages and N-stages was slightly different. Gemella and Bacillales were enriched in T1/T2-stage patients and the non-lymphatic metastasis group, while Spirochaetae and Flavobacteriia were enriched in the extranodal extension negative group. Taken together, high-throughput DNA sequencing in combination with clinicopathological features facilitated us to characterize special patterns of oral tumor microbiome in different disease developmental stages.

Intratumor microbiome: selective colonization in the tumor microenvironment and a vital regulator of tumor biology

“…Conversely, alcohol ingestion resulted in increased levels of Neisseria 74 . And the fact that Neisseria is more abundant in outer tumor tissues 57 is also consistent with the role of Neisseria in promoting carcinogenesis. Moreover, pathogenic bacteria such as Bartonella henselae could transfer their conjugative DNA into nucleus of human cells by the VirB/VirD4 type IV secretion system, 75 which could be another source of genetic mutations.…”

“…When comparing different tissue parts of oral cancers, the microbiome of tumor tissues had a greater alpha diversity, while minor differences in diversity existed between outer tumor tissues and inner tumor tissues. Nevertheless, Fusobacterium , Neisseria , Porphyromonas , and Alloprevotella were more abundant in outer tumor tissues, while Prevotella , Selenomonas , and Parvimonas were enriched in inner tumor tissues 57 …”

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

“…These microorganisms play a role in tumor development and impact the prognosis of immunotherapy by influencing immunity, particularly T cells involved in immunotherapy responses. 38 In PDAC, F. nucleatum present in tumor cells promotes the proliferation and migration of PDAC cells by facilitating autocrine and paracrine cytokine secretion in cancer cells. 40 In contrast,…”

“…The abundance of Fusarium nucleatum is significantly higher in patients with esophageal squamous cell carcinoma (ESCC) than that in healthy individuals 37 . Similarly, this altered abundance of F. nucleatum distinguishes patients with colorectal from those with oral cancers 38,39 . In pancreatic ductal carcinoma (PDAC), F. nucleatum present in tumor cells promotes the proliferation and migration of PDAC cells by inducing the autocrine and paracrine secretion of cytokines from cancer cells 40 .…”

“…The enrichment of PDAC with microorganisms linked to the onset of oral or intestinal diseases, including Campylobacter spp., F. nucleatum , and Leptospira , is consistent with the findings of previous studies identifying microorganisms associated with pancreatic and gastrointestinal diseases. These microorganisms play a role in tumor development and impact the prognosis of immunotherapy by influencing immunity, particularly T cells involved in immunotherapy responses 38 . In PDAC, F. nucleatum present in tumor cells promotes the proliferation and migration of PDAC cells by facilitating autocrine and paracrine cytokine secretion in cancer cells 40 .…”