Pan-Cancer analysis of the expression and regulation of matrisome genes across 32 tumor types

Valerio Izzi; Juho Lakkala; Raman Devarajan; Anni Kääriäinen; Jarkko Koivunen; Ritva Heljasvaara; Taina Pihlajaniemi

doi:10.1016/j.mbplus.2019.04.001

Pan-Cancer analysis of the expression and regulation of matrisome genes across 32 tumor types

Matrix Biol Plus. 2019 Apr 6:1:100004. doi: 10.1016/j.mbplus.2019.04.001. eCollection 2019 Feb.

Authors

Valerio Izzi¹, Juho Lakkala¹, Raman Devarajan¹, Anni Kääriäinen¹, Jarkko Koivunen¹, Ritva Heljasvaara^{1

2}, Taina Pihlajaniemi¹

Affiliations

¹ Oulu Center for Cell-Matrix Research and Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland.
² Centre for Cancer Biomarkers (CCBIO), Department of Biomedicine, University of Bergen, N-5009 Bergen, Norway.

Abstract

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.

Keywords: Gene regulation; Matrisome; Pan-Cancer; Prognostic; Therapy; Tumor.