CXCR4在多发性骨髓瘤中对卡菲佐米疗效及预后的影响

Effect of CXCR4 on the Treatment Response and Prognosis of Carfilzomib in Multiple Myeloma

目的:探讨CXCR4对卡菲佐米(CFZ)治疗多发性骨髓瘤(MM)患者的效果及预后的影响。方法:下载在线数据库Gene Expression Omnibus(GEO)中含两种耐CFZ的MM细胞株(KMS11/CFZ及KMS34/CFZ)以及相对应的亲本株KMS11和KMS34基因表达谱数据的数据集GSE69078。分析差异表达基因(DEGs)并构建蛋白-蛋白互作(PPI)网络,获得CFZ耐药关键基因。最终,以MMRF-CoMMpass研究数据作为验证数据集探讨CFZ耐药关键基因的临床意义。结果:共鉴定出44个上调DEGs和46个下调DEGs,通过PPI网络分析筛选出前10位关键基因(CCND1、CXCR4、HGF、PECAM1、ID1、HEY1、TCF4、HIST1H4J、HIST1H2BD及HIST1H2BH)。MMRF-CoMMpass数据显示,C-X-C基序趋化因子受体4(CXCR4)高表达与较高的复发/进展率相关,且CXCR4高表达患者的总生存(OS)率显著降低(P=0.013)。结论:CXCR4高表达可能与MM患者CFZ获得性耐药相关,有助于在治疗前筛选潜在的CFZ敏感患者,并有望为CFZ耐药MM提供新的治疗靶点。

Objective: To explore the effect of CXCR4 on the treatment response and prognosis of Carfilzomib(CFZ) in multiple myeloma. Methods: Dataset GSE69078 based on microarray data from two CFZ-resistant MM cell lines and their corresponding parental cell lines(KMS11-KMS11/CFZ and KMS34-KMS34/CFZ) were downloaded from Gene Expression Omnibus(GEO). Differentially expressed genes(DEGs) were identified, and Protein-protein interaction(PPI) network was established to identify the key genes involved in CFZ resistance acquisition. Finally, the prognostic roles of the CFZ risistance key genes in MM using MMRF-CoMMpass data study was verified. Results: 44 up-regulated and 46 down-regulated DEGs were identified. Top 10 hub genes(CCND1, CXCR4, HGF, PECAM1, ID1, HEY1, TCF4, HIST1 H4 J, HIST1 H2 BD and HIST1 H2 BH) were identified via Protein-protein interaction(PPI) network analysis. The CoMMpass data showed that high CXCR4 expression showed correlation to relative higher relapse and progress rates and the overall survival was significant decreased in high CXCR4 patients(P=0.013). Conclusion: CXCR4 perhaps plays a crucial role in CFZ acquired resistance, which might help identifying potential CFZ-sensitive patients before treatment and providing a new therapeutic target in CFZ-resistant MM.