PSMB7 Is a Key Gene Involved in the Development of Multiple Myeloma and Resistance to Bortezomib

• Main Authors: Dong Wu, Jiyu Miao, Jinsong Hu, Fangmei Li, Dandan Gao, Hongli Chen, Yuandong Feng, Ying Shen, Aili He
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-07-01
• Series: Frontiers in Oncology
• Subjects: multiple myeloma; proteasome inhibitor; PSMB7; WGCNA; drug resistance
• Online Access: https://www.frontiersin.org/articles/10.3389/fonc.2021.684232/full

Multiple myeloma (MM), the second most commonly diagnosed hematologic neoplasm, is the most significant clinical manifestation in a series of plasma cell (PC) dyscrasia. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM), approximately 1% or 10% of which, respectively, can progress to MM per year, are the premalignant stages of MM. The overall survival (OS) of MM is significantly improved by the introduction of proteasome inhibitors (PIs), but almost all MM patients eventually relapse and resist anti-MM drugs. Therefore, it is crucial to explore the progression of MM and the mechanisms related to MM drug resistance. In this study, we used weighted gene co-expression network analysis (WGCNA) to analyze the gene expression of the dynamic process from normal plasma cells (NPC) to malignant profiling PC, and found that the abnormal gene expression was mainly concentrated in the proteasome. We also found that the expression of one of the proteasomal subunits PSMB7 was capable of distinguishing the different stages of PC dyscrasia and was the highest in ISS III. In the bortezomib (BTZ) treated NDMM patients, higher PSMB7 expression was associated with shorter survival time, and the expression of PSMB7 in the BTZ treatment group was significantly higher than in the thalidomide (Thai) treatment group. In summary, we found that PSMB7 is the key gene associated with MM disease progression and drug resistance.