Evaluation of TMED9, DNAJC1, LMAN2, COPE and KDELR1 Biomarkers in Patients with Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Abstract

Plasma cell dyscrasias (PCD) are a heterogeneous group of hematological diseases. The TMED9, KDELR1, DNAJC1, COPE, and LMAN2 genes identified from our transcriptome data are highly importance and specific. We determined the protein-protein interac-tions of these genes in STRING v11.5 higher than expected (PPI enrichment p value 1.71e-06). We evaluated the prognostic bio-marker status of these genes in PCD by quantitative method (qRT-PCR) of 38 Multiple Myeloma (MM), 23 Monoclonal Gammopathy of Undetermined Significance (MGUS) and 16 control groups. We found significant gene expression levels increase among these three study groups of these genes (p< 0.001). As a single marker, DNAJC1 exhibited the best ability for discriminating MM from MGUS (AUC= 83%) and MM from control (AUC= 88.7%). In addition to this, the combination of five genes exhibited the highest efficacy of discriminating MM from the control (AUC= 90.90%). The combination of KDELR1, COPE, TMED9 and DNAJC1 exhibited the best ability to discriminate MM group from MGUS group (AUC= 86.80%). In conclusion, we showed that DNAJC1 alone, as well as the combination of other selected genes, can be valuable targets in the pathogenesis of myeloma. These new biomarkers have been evaluated for the first time in PCD and we think they will contribute to the discovery of potential anti-myeloma therapeutic targets in the future.