The microenvironment plays a central role in cancer, and neoplastic cells actively shape it to their needs by complex arrays of extracellular matrix (ECM) proteins, enzymes, cytokines and growth factors collectively referred to as the matrisome. Studies on the cancer matrisome have been performed for single or few neoplasms, but a more systematic analysis is still missing. Here we present a Pan-Cancer study of matrisome gene expression in 10,487 patients across 32 tumor types, supplemented with transcription factors (TFs) and driver genes/pathways regulating each tumor's matrisome. We report on 919 TF-target pairs, either used specifically or shared across tumor types, and their prognostic significance, 40 master regulators, 31 overarching regulatory pathways and the potential for druggability with FDA-approved cancer drugs. These results provide a comprehensive transcriptional architecture of the cancer matrisome and suggest the need for development of specific matrisome-targeting approaches for future therapies.
Relapse of acute myeloid leukemia (AML) is still dramatically frequent, imposing the need for early markers to quantify such risk. Recent evidence point to a prominent role for extracellular matrix (ECM) in AML, but its prognostic value has not yet been investigated. Here we have investigated whether the expression of a 15-ECM gene signature could be applied to clinical AML research evaluating a retrospective cohort of 61 AML patients and 12 healthy donors. Results show that patients whose ECM signature expression is at least twice as that of healthy donors have considerably longer relapse-free survival, with further stage-specific therapy outcomes.
without urogenital symptoms are more frequent. We found no case of adenoviruria after stem cell transplantation, so we must conclude that this virus is not that important in the adult population like it is in paediatric stem cell transplantation.5 Interestingly, BK viruria was significantly associated with acute renal failure. Acute renal failure was described in retrospective analysis before, so we must conclude that BK virus can also lead to nephropathy in allogeneic stem cell transplantation like it is well known in kidney transplantation. 4 We found no association with polyomavirus BK and JC with GvHD contrary to what was described in other studies. 6 Regarding GvHD prophylaxis, our study was quite homogenous, since all patients received alemtuzumab.Other studies had more heterogenous populations or all participants received antithymogloboline for GvHD prophylaxis. 6 We conclude that urological complications, especially polyomavirus associated urogenital infections, are important and considerable during adult allogeneic stem cell transplantation.
ACKNOWLEDGMENTSThe authors would like to thank all participating patients and all nurses or study nurses of the University Medicine Greifswald Department of Hematology/Oncology who made this study a success. Thank you for your great help and advice! ORCID Laila Schneidewind
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