A new proteomic approach to detect and characterise microorganisms in peritoneal mucinous carcinomatosis

Pseudomyxoma peritonei (PMP) is a rare malignancy and the paradigm of Peritoneal Mucinous Carcinomatosis, which causes the continuous accumulation of mucus-secreting cells and glycoprotein-rich mucus in the abdomen. The only available treatment involves complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. Despite this aggressive management, relapses are common in PMP, leading to debilitating symptoms and a fatal end. It's therefore important to look for ways to improve treatment and better understand the pathogenesis of the disease. In this context, microorganisms have previously been detected in PMP by genomic approaches and antibacterial treatment has been suggested, but data are limited. Our group aimed to develop the first method based on a "proteomic approach" to test and characterise the presence of microorganisms in mucinous tumour tissues.

Samples obtained from patients during CRS-HIPEC surgery were treated with our pioneering protein isolation protocol and then analysed by nanoHPLC-MS/MS. To identify and characterise the presence of microorganisms in the tumour tissue, a new human and microbial protein database was created.

Our results demonstrate for the first time the presence of fungal proteins in mucin samples from PMP tumours, both low and high grade (Figure 1), and was validated by histological staining of tumoral tissue at our pathology service. This work presents a novel proteomic and bioinformatic approach to identify the presence of microbiota. This is in line with the literature where different genera of bacteria and fungi have been identified by genomic approaches in different types of cancer. However, further research is needed to determine the role of this advance in the pathogenesis of mucinous tumours, to understand the mechanisms of oncogenesis and to develop better therapeutic strategies for these patients.

Funding sources: This work is supported by Instituto de Salud Carlos III (ISCIII), "PI22/01213"; co-funded by the European Union, and by Asociación Española contra el Cáncer, "PRYES223170ARJO".