International Journal of Hematology and Oncology 2023, Vol 33, Num 2 Page(s): 092-102
Evaluation of TMED9, DNAJC1, LMAN2, COPE and KDELR1 Biomarkers in Patients with Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Melda SARIMAN1, Burcu SALMAN YAYLAZ1, Aysegul YABACI TAK2, Mesut AYER1, Sema SIRMA EKMEKCI3, Ilknur SUER4, Kivanc CEFLE4, Sukru PALANDUZ4, Sukru OZTURK4, Meliha NALCACI5, Neslihan ABACI1

1Istanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul, Turkey
2Bezmialem Vakif University, Faculty of Medicine, Department of Biostatistics and Medical Informatics, Istanbul, Turkey
3University of Health Sciences, Istanbul Haseki Training and Research Hospital, Clinical Hematology, Istanbul, Turkey
4Istanbul University, Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Medical Genetics, Istanbul, Turkey
5Istanbul University, Istanbul Faculty of Medicine, Department of Internal Medicine Division of Hematology, Istanbul, Turkey

Keywords: DNAJC1, Biomarker, Multiple myeloma, MGUS, Plasma cell dyscrasias
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 interactions of these genes in STRING v11.5 higher than expected (PPI enrichment p value 1.71e-06). We evaluated the prognostic biomarker
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.