Analysis of microbiome in gastrointestinal stromal tumors: Looking for different players in tumorigenesis and novel therapeutic options

Abstract

Preclinical forms of gastrointestinal stromal tumor (GIST), small asymptomatic lesions, called microGIST, are detected in approximately 30% of the general population. Gastrointestinal stromal tumor driver mutation can be already detected in microGISTs, even if they do not progress into malignant cancer; these mutations are necessary, but insufficient events to foster tumor progression. Here we profiled the tissue microbiota of 60 gastrointestinal specimens in three different patient cohorts—micro, low‐risk, and high‐risk or metastatic GIST—exploring the compositional structure, predicted function, and microbial networks, with the aim of providing a complete overview of microbial ecology in GIST and its preclinical form. Comparing microGISTs and GISTs, both weighted and unweighted UniFrac and Bray–Curtis dissimilarities showed significant community‐level separation between them and a pronounced difference in Proteobacteria, Firmicutes, and Bacteroidota was observed. Through the LEfSe tool, potential microbial biomarkers associated with a specific type of lesion were identified. In particular, GIST samples were significantly enriched in the phylum Proteobacteria compared to microGISTs. Several pathways involved in sugar metabolism were also highlighted in GISTs; this was expected as cancer usually displays high aerobic glycolysis in place of oxidative phosphorylation and rise of glucose flux to promote anabolic request. Our results highlight that specific differences do exist in the tissue microbiome community between GIST and benign lesions and that microbiome restructuration can drive the carcinogenesis process.

Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours

“…It was also shown that sunitinib itself could induce a significant shift in the microbiome that could affect further treatment [ 107 ]. Recent data has also shown that tissue microbial composition of GIST and microGIST exhibit a difference in the abundance of various bacteria, such as the enrichment of Proteobacteria in GIST samples, hypothesising that the microbiome restructuration can drive the carcinogenesis process [ 108 ]. While microbiome studies are scarce in the GIST, the microbiome likely plays a significant role during the treatment with TKI or immunotherapy.…”

An Unusual Case of Suspected Metastatic Gastrointestinal Stromal Tumor Complicated by Streptococcus Intermedius Pyogenic Liver Disease

“…The postulated mechanisms by which GISTs cause bacterial infections include systemic invasion via mucosal breakdown by the tumor or concurrent travel of the bacteria through a vehicular-mediated mechanism involving tumor translocation [ 14 ]. Emerging studies have also noted a relationship between gut microbiota dysbiosis and the development of GIST, which we would recommend further exploration [ 19 ]. Nonetheless, if there is a concern for liver metastasis, it is recommended that patients undergo diagnostic workup for pyogenic liver abscesses as well, so they are promptly initiated on appropriate antibiotics [ 18 ].…”