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.

中文翻译：

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多发性骨髓瘤患者CHEK1表达与临床病理特征之间的强相关性。

多发性骨髓瘤（MM）是最常见的恶性肿瘤之一，MM患者的临床结局仍然很差。我们的目标是筛选与MM患者的临床病理特征和生存相关的生物标志物。构建了基因共表达网络，以筛选与MM的国际分期系统（ISS）的三个阶段相关的中心基因。进行了毂基因的功能分析和蛋白质-蛋白质相互作用分析。选择了CHEK1（与MM的ISS阶段最相关的基因）进行进一步的临床验证。总共确定了780个与MM的ISS阶段相关的中枢基因。对中枢基因的功能富集分析表明，这些基因大多富含《京都议定书》的基因和基因组百科全书（KEGG）中涉及细胞增殖和免疫应答的几种基因本体论（GO）术语和途径。新诊断患者的MM细胞中蛋白质检查点激酶I（CHEK1）的基因表达增加了（与正常浆细胞相比，P = 0.0304）和复发患者（P = 0.0002）。同时，CHEK1更加提高在MM患者与II期疾病（P = 0.0321）和III期疾病（P比在那些与I期疾病= 0.0076）。生存分析表明，以CHEK1低表达为特征的MM患者在进展时间，无事件生存和总体生存方面具有更好的临床结局。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诊断的生物标志物。