Weighted Gene Co-expression Network Analysis of CXCL13, CXCR5, and associated genes in multiple myeloma

Abstract

Abstract Multiple myeloma (MM) is characterized by the neoplastic proliferation of plasma cells. In 2018, there were approximately 30,770 new cases diagnosed and about 12,770 dead. Characterizing its molecular phenotypes is important for effective treatment of MM and predicting relapse. CXCL13-CXCR5 interactions are involved in malignancy cell homing, adhesion, signal transduction, and calcium flux, all of which promote MM progression. Here, we analyzed RNA-sequence data from matched normal, primary and relapsed MM cases. Patient control mRNA samples matched primary tumor and relapse samples were acquired from the database of Genotypes and Phenotypes to evaluate the mRNA expression patterns of CXCL13, CXCR5 and associated genes in MM. Bioinformatics tools were to integrate published genomic data from MM patients (n=480) and identify genes associated with CXCL13-CXCR5 signaling. DESeq analysis was used to determine differentially expressed genes between normal tissues, primary tumor, and relapse groups. Weighted gene co-expression network analysis identified clusters of genes significantly associated with the molecular phenotypes of MM. Notably, gene expression is driven by NFAT and JUN, known to be activated by the CXCL13-CXCR5 axis, and plasma cell signaling pathways significantly correlated with select MM molecular phenotypes and patient survival. Ingenuity pathway analysis was performed to analyze upstream regulators, gene interaction and canonical pathways. Taken together, our data show CXCR5-CXCL13 signaling networks are significantly expressed and associated with MM pathogenesis and plasma clonality. This study provides a better understanding of the heterogeneous nature of MM and the role of CXCL13-CXCR5 axis in MM.