SH2D2A is an indicator of favourable prognosis in bladder cancer and is enriched in activated Treg cells

Given 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 ⁺ IL2RA ^hi 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 and diversifying possible targets for immunotherapies.