Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Crit Rev Eukaryot Gene Expr. 2020;30(4):349-357. doi: 10.1615/CritRevEukaryotGeneExpr.2020027084.
Multiple myeloma (MM) is one of the most common malignancies, and the clinical outcome of patients with MM remains poor. Our objective is to screen biomarkers correlated with clinicopathological features and survival of patients with MM. A gene co-expression network was constructed to screen hub genes related to the three stages in the International Staging System (ISS) of MM. Functional analysis and protein-protein interaction analysis of the hub genes was performed. CHEK1, a gene most related to the ISS stages of MM, was selected for further clinical validation. A total of 780 hub genes correlated with ISS stages of MM were identified. Functional enrichment analysis of hub genes suggested that these genes were mostly enriched in several gene ontology (GO) terms and pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) that were involved in cell proliferation and immune response. Expression of the gene for the protein checkpoint kinase I (CHEK1) was increased in MM cells from newly diagnosed patients (P = 0.0304) and relapsed patients (P = 0.0002) as compared to normal plasma cells. Meanwhile, CHEK1 was increased more in MM patients with stage II disease (P = 0.0321) and stage III disease (P = 0.0076) than in those with stage I disease. Survival analysis indicated that MM patients in the group characterized by low CHEK1 expression were associated with better clinical outcomes in terms of time to progression, event-free survival, and overall survival. High expression of CHEK1 predicted poor clinical characteristics of MM patient, and our results indicate that it can be considered a biomarker for the diagnosis of MM.
多发性骨髓瘤(MM)是最常见的恶性肿瘤之一,MM 患者的临床预后仍然较差。我们的目的是筛选与 MM 患者临床病理特征和生存相关的生物标志物。构建基因共表达网络,筛选与 MM 国际分期系统(ISS)三个阶段相关的枢纽基因。对枢纽基因进行功能分析和蛋白质-蛋白质相互作用分析。选择与 MM ISS 阶段最相关的基因 CHEK1 进行进一步的临床验证。共筛选出 780 个与 MM ISS 阶段相关的枢纽基因。枢纽基因的功能富集分析表明,这些基因主要富集在几个京都基因与基因组百科全书(KEGG)中的基因本体论(GO)术语和途径中,这些术语和途径与细胞增殖和免疫反应有关。与正常浆细胞相比,来自新诊断患者(P = 0.0304)和复发患者(P = 0.0002)的 MM 细胞中蛋白检查点激酶 I(CHEK1)的基因表达增加。同时,CHEK1 在 II 期疾病(P = 0.0321)和 III 期疾病(P = 0.0076)患者中较 I 期疾病患者表达更高。生存分析表明,CHEK1 低表达组 MM 患者的无进展时间、无事件生存和总生存的临床结局更好。CHEK1 的高表达预示着 MM 患者的临床特征较差,我们的结果表明,它可以被认为是 MM 的诊断生物标志物。