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Immune profile dysregulation of high grade- compared to low grade-pseudomyxomas
Charlotte Bourgin1, Maxime Golias1, Emilie Ollivier2
1Nantes Université, CNRS, UMR 6286, US2B, Nantes, France; Institut de Cancérologie de l'Ouest, "Tumor Heterogeneity and Precision Medicine" Laboratory, Saint-Herblain, France.
Background:
Pseudomyxoma peritonei is a rare and poorly understood cancer. The histological characteristics that classify pseudomyxoma as either low-grade or high-grade are major prognostic factors. The present study aimed to identify differentially expressed genes in low-grade and high-grade pseudomyxomas using transcriptomic analysis, in order to improve our understanding of their pathophysiology.
Methods:
Two cohorts of pseudomyxoma peritonei FFPE samples composed by 13 low grade and 11 high grade tumours respectively were selected. The expression of several biomarkers (CK7, CK20, MUC2, MUC5AC, Ki67) were analysed by immunohistochemistry. Gene expression profiles were studied using Nanostring™ technology and included the tumour signalling 360™ panel (760 tumour signalling related genes and 20 internal reference controls) and the inflammation v2 panel (249 inflammation-related human genes and 6 internal reference controls).
Results:
The study revealed distinct transcriptomic profiles of the immune response in low grade and high grade, indicating dysregulation of immune cell migration and/or chemotaxis, as well as modulation of cellular metabolic activities and cell signalling. In addition, in high grade pseudomyxoma peritonei, there are genes and signalling pathways linked to the response to lipopolysaccharides and bacterial molecules were also downregulated. Our results strengthen both the role of immune response and the role of bacterial involvement in pseudomyxoma peritonei pathophysiology.
