Wu Dong, Miao Jiyu, Hu Jinsong, Li Fangmei, Gao Dandan, Chen Hongli, Feng Yuandong, Shen Ying, He Aili
Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Cell Biology and Genetics, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Front Oncol. 2021 Jul 23;11:684232. doi: 10.3389/fonc.2021.684232. eCollection 2021.
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.
多发性骨髓瘤(MM)是第二常见的血液系统肿瘤,是一系列浆细胞(PC)发育异常中最显著的临床表现。意义未明的单克隆丙种球蛋白病(MGUS)和冒烟型MM(SMM)分别约有1%或10%每年会进展为MM,它们是MM的癌前阶段。蛋白酶体抑制剂(PIs)的引入显著提高了MM的总生存期(OS),但几乎所有MM患者最终都会复发并对抗MM药物产生耐药性。因此,探索MM的进展以及与MM耐药相关的机制至关重要。在本研究中,我们使用加权基因共表达网络分析(WGCNA)来分析从正常浆细胞(NPC)到恶性特征性PC的动态过程中的基因表达,发现异常基因表达主要集中在蛋白酶体。我们还发现蛋白酶体亚基之一PSMB7的表达能够区分PC发育异常的不同阶段,且在国际分期系统(ISS)III期最高。在硼替佐米(BTZ)治疗的新诊断MM(NDMM)患者中,较高的PSMB7表达与较短的生存时间相关,且BTZ治疗组中PSMB7的表达显著高于沙利度胺(Thai)治疗组。总之,我们发现PSMB7是与MM疾病进展和耐药相关的关键基因。