Characterisation of the Intratumoral Microbiome in Gastric Adenocarcinoma: to a Personalised Medicine

Gastric Adenocarcinoma

Gastric cancer, intratumoral microbiota, circulating tumour cells, biomarkers

In this study, gastric tumours and adjacent healthy mucosa will be collected from gastric cancer patients operated on for curative purposes. From this material, presence and characterisation of intratumoral bacteria will be determined. Intratumoral microbiota composition will be compared with healthy adjacent tissue, and the intratumoral microbiota composition will also be compared between different tumor types. The different bacterial signatures that we will characterise may be used as biomarkers.

Gastric adenocarcinoma is mainly linked to Helicobacter pylori infection, and this bacterium is classified as a class 1 carcinogen by the WHO. However, infection with this bacterium alone is not sufficient for the development of gastric adenocarcinoma. It is now recognised that environmental factors such as the digestive microbiota influence carcinogenesis. Improved sequencing techniques have shown that some tumours contain intracellular bacteria and that these are specific to the origin of the tumour. A study describing the existence of intratumoral bacteria was carried out on 7 different tumour types excluding gastric cancer. Gastric adenocarcinoma is a cancer with a poor prognosis, treatment, based mainly on surgery combined with conventional chemotherapy, is not very effective with a 5-year survival rate of less than 20%. Except for Her2+ cases, there is no specific treatment. It is therefore now essential to develop targeted and effective treatments. The objective of this project is to define whether intratumoral bacteria exist in gastric cancer. To achieve this, tumours and adjacent healthy mucosa from patients with gastric cancer will be collected and analysed in INSERM U1312 laboratory. The biological material studying consists only of remnants of biopsies of gastric tumours and adjacent healthy tissues, which are not needed in the pathology laboratory, from patients who undergo gastrectomy as part of their cancer management Two blood tubes for the isolation of possible circulating tumour cells will also be collected. From these materials, the presence of intratumoral bacteria will be determined by immunohistochemistry targeting components of the bacterial wall, by RNAscope® targeting 16S ribosomal RNA (16S rRNA) and by real-time quantitative PCR targeting 16S rDNA. Characterisation of the intratumoral microbiota will be performed by sequencing 16S rDNA gene. The collected blood will be tested for the presence of CSCs and, if CSCs are detected, the microbiota will be tested and characterised using the same techniques described above. The primary endpoint will be the evidence of an intratumoral microbiota and its taxonomic description.

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