A TRPV2 interactome-based signature for prognosis in glioblastoma patients.

Pau Doñate-Macián,Alex Perálvarez-Marín,Antonio Gómez,Irene R Dégano

doi:10.18632/oncotarget.24843

Abstract

Proteomics aids to the discovery and expansion of protein-protein interaction networks, which are key to understand molecular mechanisms in physiology and physiopathology, but also to infer protein function in a guilt-by-association fashion. In this study we use a systematic protein-protein interaction membrane yeast two-hybrid method to expand the interactome of TRPV2, a cation channel related to nervous system development. After validation of the interactome in silico, we define a TRPV2-interactome signature combining proteomics with the available physio-pathological data in Disgenet to find interactome-disease associations, highlighting nervous system disorders and neoplasms. The TRPV2-interactome signature against available experimental data is capable of discriminating overall risk in glioblastoma multiforme prognosis, progression, recurrence, and chemotherapy resistance. Beyond the impact on glioblastoma physiopathology, this study shows that combining systematic proteomics with in silico methods and available experimental data is key to open new perspectives to define novel biomarkers for diagnosis, prognosis and therapeutics in disease.

Highlights

Among transient receptor potential (TRP) channels, the TRP vanilloid 2 (TRPV2) cation channel is a thermal, mechanical, and lipid sensor related to a wide span of physiological roles such as thermogenesis, cardiac structure, neuromuscular development and function, etc. [1,2,3,4]
We used a guilt-by-association discovery approach to unravel the role of TRPV2 and its protein-protein interactions (PPI) in central nervous system (CNS) pathophysiology
The putative TRPV2 interactome consists of TRPV2 + 22 proteins derived from canonical immunoprecipitation studies and a systematic PPI screening among which ABR, ARL15, NTM, Opalin, SACM1L and ST18, seem to have the strongest interaction with TRPV2

Summary

Introduction

Among transient receptor potential (TRP) channels, the TRP vanilloid 2 (TRPV2) cation channel is a thermal, mechanical, and lipid sensor related to a wide span of physiological roles such as thermogenesis, cardiac structure, neuromuscular development and function, etc. [1,2,3,4]. Among transient receptor potential (TRP) channels, the TRP vanilloid 2 (TRPV2) cation channel is a thermal, mechanical, and lipid sensor related to a wide span of physiological roles such as thermogenesis, cardiac structure, neuromuscular development and function, etc. To assess TRPV2 function, several attempts have focused on TRPV2 protein-protein interactions (PPI). PPI screenings rely in the understanding of a protein-of-interest physiological function using a guiltby-association approach [8]. These PPI have to be further validated in an appropriate physiological system, becoming the time-limiting step for the discovery of protein-function or protein-disease associations. In a guilt-by-association fashion the TRPV2-NGF-1 interaction would suggest www.oncotarget.com the role of TRPV2 in neural development, confirming previous results relating TRPV2 to central nervous system (CNS) physiology [7, 9]

Methods

Results

Conclusion