Discovery and validation of a glioblastoma co-expressed gene module

// Leland J. Dunwoodie 1 , William L. Poehlman 1 , Stephen P. Ficklin 2 and Frank Alexander Feltus 1 1 Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634, USA 2 Department of Horticulture, Washington State University, Pullman, WA 99164, USA Correspondence to: Frank Alexander Feltus, email: ffeltus@clemson.edu Keywords: glioblastoma; systems biology; gene co-expression networks; complement system; cancer Received: July 28, 2017      Accepted: January 09, 2018      Published: January 13, 2018 ABSTRACT Tumors exhibit complex patterns of aberrant gene expression. Using a knowledge-independent, noise-reducing gene co-expression network construction software called KINC, we created multiple RNAseq-based gene co-expression networks relevant to brain and glioblastoma biology. In this report, we describe the discovery and validation of a glioblastoma-specific gene module that contains 22 co-expressed genes. The genes are upregulated in glioblastoma relative to normal brain and lower grade glioma samples; they are also hypo-methylated in glioblastoma relative to lower grade glioma tumors. Among the proneural, neural, mesenchymal, and classical glioblastoma subtypes, these genes are most-highly expressed in the mesenchymal subtype. Furthermore, high expression of these genes is associated with decreased survival across each glioblastoma subtype. These genes are of interest to glioblastoma biology and our gene interaction discovery and validation workflow can be used to discover and validate co-expressed gene modules derived from any co-expression network.