Th140 - SH2D2A Is an Indicator of Favourable Prognosis in Bladder Cancer and Is Enriched in Activated Treg Cells

Johan Georg Visser – Postdoc, Departement of Molecular Medicine, University of Oslo; Alvaro Köhn-Luque – Senior Researcher, Departement of Biostatistics, University of Oslo; Andreas Lossius – Associate Professor, Departement of Molecular Medicine, University of Oslo; Anne Spurkland – Professor, Departement of Molecular Medicine, University of Oslo

Abstract Text: The significance of RNA sequencing (RNA-seq) in modern medical research and diagnostics cannot be understated, and its importance has brought about an expansion in the quality and accessibility of the method and its data output. The conventional approach that has defined much of science begins with measurable phenomena, natural or otherwise, and proceeds, by identification of the mutations or aberrations that produce it, to a gene’s function. While this approach has produced a great body of scientific progress, its Achille’s heel is its reliance on measurable phenomena. With the expanding availability of RNA-seq and other such high dimensional data it is now possible to consider a complementary approach working in the opposite direction i.e., from transcriptomics up towards protein function. This approach may prove fruitful in producing information on the function of cytosolic-bound proteins such as adapter proteins.
To test the validity of this method, we made use of several public datasets to interrogate the cancer-specific role of the adapter protein SH2D2A: a protein enriched in T and NK cells, and a known interactor of the kinase LCK, whose function remains uncertain. We found that SH2D2A is a favourable marker for prognosis in urothelial bladder cancer (BLCA). Digging further, we identified a population of SH2D2A+ FOXP3+ IL2RAhi activated Tregs as the main expressors of SH2D2A in BLCA. This suggests that the expression of SH2D2A in these Tregs contributes to a beneficial prognostic effect. Further comprehension of SH2D2A's function in these cells holds the potential for advancing treatment in BLCA.