Abstract
Multiple myeloma (MM) is a disease in which abnormal plasma cells proliferate and secrete monoclonal immunoglobulin in the bone marrow. The main characteristic of plasma cells is the expression of the cell surface antigen syndecan-1 (CD138). However, the expression of CD138 is limited to terminally differentiated plasma cells during B cell development. A small subpopulation (2~5%) of human MM cells that lack CD138 expression has been shown to possess enormous proliferation potential in vitro experiment and in animal models, and they also can differentiate into CD138+ plasma cells. Thus, this small subset of MM cells was regarded as myeloma cancer stem cell (MCSC). However, its characteristics associated with the pathogenesis of MM remain unclear. In this study, we analyzed the gene expression data of CD138 cell lines downloaded from Gene Expression Omnibus (GEO) database. Limma package in RStudio was used to identify differentially expressed genes (DEGs). Genes enrichment and protein-protein interaction (PPI) network analysis were performed on DAVID and STRING databases. Furthermore, overall survival (OS) analysis in MM patient was utilized to screen out the hub-genes closely associate with the MM pathogenesis process. Hub-genes expression validation and receiver operating characteristic curve (ROC) analysis was performed in different stages of plasma cell disorder diseases. Finally, we verified these findings in MM patient samples. Through integrated bioinformatics analysis of MM CD138- and CD138+ cell lines, we found that CDC7, CDK1, and CHK1 are highly expressed in CD138- MM cells. These genes are crucial in the G2/M phase of the cell cycle pathway, which is closely related to the malignant proliferation in various tumor cells. Of note, we found that patients with high expression of CDC7, CDK1, and CHK1 had shorter overall survival time. The expression of CHK1 was significantly increased in MM cells compared with normal plasma cell (NPC) and MGUS. More importantly, we further clarified that the expression of CHK1 in release/refraction MM (R/R MM) has obviously increased compared with new diagnosed MM (ND MM).
Highlights
Multiple myeloma (MM) is an incurable malignant plasma cell disease and is the second most common hematology malignant tumor [1]
In the present study, integrated bioinformatics analysis was performed on the GSE31305 dataset, which contains CD138- and CD138+ human MM cell lines
CD138 is expressed in the terminal differentiation stage of plasma cells, but lost in the early stages of B cell and highly clonal plasma cells [15, 16]
Summary
Multiple myeloma (MM) is an incurable malignant plasma cell disease and is the second most common hematology malignant tumor [1]. Numerous advances are available for the treatment of MM, such as immunomodulators drugs (IMiDs), proteasome inhibitors (PI), monoclonal antibodies, autologous stem-cell transplantation (ASCT), and chimeric antigen receptor T(CAR-T) cell therapy, [2,3,4]. The utilization of these therapies has dramatically improved the overall survival of MM patients. A small number of myeloma cells have the ability of pathogenicity and tumorigenic These cells are called multiple myeloma "stem cells" [7]. A better understanding of the distinction between CD138- and CD138+ MM plasma cellular characterization will help to develop new targets and strategies for the prognosis and treatment of MM
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