Abstract LB-132: The role of CXCL13, its sole receptor CXCR5, and associated genes in multiple myeloma progression

Abstract

Abstract Multiple myeloma (MM) is characterized by the neoplastic proliferation of plasma cells producing monoclonal immunoglobulin in blood, bone marrow, and urine. In 2018, it was estimated that approximately 30,770 new cases would be diagnosed (16,400 in men and 14,370 in women) and about 12,770 deaths were expected to occur (6,830 in men and 5,940 in women). MM is a heterogenous disease; thus, characterizing their molecular phenotypes, plays a significant role in prognosis and effective treatment of MM and relapse cases. Certain chemokine and it sole receptor (CXCL13 and CXCR5) has been shown to contribute to the progression and metastasis of several types of cancers. CXCL13 and CXCR5 are expressed by cells in the microenvironment of bone marrow and function in malignancy cell homing, adhesion, signal transduction, and calcium flux, all of which promote MM progression. To identify the potential function of relevant somatic mutations and gene expression in MM causing clonal evolution and lethality, 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 dbGap (database of Genotypes and Phenotypes) to evaluate the mRNA expression of CXCL13-CXCR5 and associated genes in MM progression. A bioinformatics strategy was used to integrate published genomic data from these MM patients (n=240) and teased out genes associated with CXCL13-CXCR5 signaling. DESeq analysis was used to determine differentially expressed genes between normal tissues, primary tumor and relapse groups. Our preliminary analysis done with Weighted Gene Co-expression Network Analysis (WGCNA) identified clusters of genes; transcription factors (NF-κB and JUN) known to be induced by the CXCL13-CXCR5 axis, and plasma cell signaling pathways. Moreover, Ingenuity pathway analysis (IPA) was performed to analyze upstream regulators, gene interaction networks and canonical pathways, which identified biological processes associated with the differentially expressed genes. We suggested that, the doubling effect of the activation of transcription factors (NF-κB and JUN) by plasma cell signaling and CXCR5-CXCL13 signaling are most likely responsible for the pathogenesis and plasma clonality of MM. This study provided a better understanding of the heterogeneous nature of MM and the role of the CXCL13-CXCR5 axis plays in MM. Therefore, CXCL13-CXCR5 and associated genes serves as a potential clinical application and a new therapeutic target for MM. Note: This abstract was not presented at the meeting. Citation Format: Olayinka O. Adebayo, Tiara Griffin, Corey Young, Courtney D. Dill, Sha'Kayla Nunez, Kaylin Carey, James W. Lillard. The role of CXCL13, its sole receptor CXCR5, and associated genes in multiple myeloma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-132.