Multiomics sequencing of the cevical cancer

Cervical cancer in women has high rates of incidence and mortality. Growing evidence suggests the key roles of the intratumor microbiome in various solid tumours. However, the intratumoral microbiome in cervical cancer is largely unknown. In this study, 16S rRNA sequencing was performed on 76 tissues to characterize the features of the intratumoral microbiome, and the highly differentially abundant bacteria Lactobacillus iners/Prevotella bivia were selected for functional verification. Flow cytometry, apoptosis, transwell migration and invasion experiments were performed in vitro; subcutaneous tumour formation and lung metastasis experiments were performed in vivo. Additionally, macrophages were cocultured with the L. iners/P. bivia supernatant to evaluate how the intratumoural microbiome affects their polarization, and tumour cell and macrophage transcriptome sequencing were subsequently performed to explore the potential molecular mechanisms involved. Metabolomic analysis of tissues and bacterial supernatants was used to search for potential carcinogens and cancer suppressors. We determined that the abundance of microbes was greater in cervical cancer tissues than in normal cervical and paracancerous tissues. The relative abundance of Prevotella was correlated with deep stromal invasion, tumour size, clinical stage and poor survival prognosis in cervical cancer patients. L. iners inhibited the proliferation and promoted the apoptosis of tumour cells, whereas P. bivia significantly promoted cervical cancer cell migration and invasion. Mechanistically, modulation of phosphorylated PI3K/AKT/mTOR signalling may be involved in the observed effects. P. bivia promoted M2 macrophage polarization by activating phosphorylated STAT3 and NF-κB, but the role of L. iners is unknown. The amino acid metabolism, carbohydrate metabolism and lipid metabolism pathways were enriched in differentially abundant metabolites such as glycine, which may be a key molecule. This study provides evidence that the intratumoural microbiome, represented by L. iners/P. bivia, affects tumour biology and macrophage polarization in patients with cervical cancer.