Identification of Cancer Biomarkers for Multi-class Diagnostics through Network Analysis of RNAseq Data of Tumor-Educated Platelets

Tumor-educated platelets (TEPs) are circulating blood cells with a distinct tumor-driven phenotype and act as carriers and protectors of metastases. To date, some studies have shown that the TEPs transcriptome can be used for cancer diagnostics. The objective of this study is to propose a procedure based on differential gene expression and differential gene co-expression analyses to identify a set of key genes for multi-class cancer diagnostics. To reach this aim, we analyzed RNA-seq data (57736 genes) of 130 subjects, of whom 40 patients with glioblastoma multiforme (GBM), 35 patients with pancreatic adenocarcinoma (PAAD), and 55 healthy donors (HC). We focused our analysis on the subset of differentially expressed genes (DEGs), and we used these genes to build and analyze the differential co-expression networks, identifying the hub genes. With this procedure, we obtained a restricted set of DEGs that maximize the accuracy in classifying patients according to their conditions (GBM, PAAD, or HC). Indeed, we validated our results by comparing the achieved classification accuracy with that resulting from random selections of DEGs and we obtained that genes selected by differential co-expression (DCE) network analysis have greater predictive power than any other set of differentially expressed genes, including using all of them.