Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-059 Lublin, Poland.
Body Composition Research Laboratory, Department of Preclinical Sciences, Medical University of Lublin, 20-059 Lublin, Poland.
Cells. 2023 Mar 28;12(7):1029. doi: 10.3390/cells12071029.
The gene encodes an oncoprotein, CIP2A, which inhibits the phosphorylation of the Akt kinase B, stabilizes the c-Myc protein, and, through that, promotes cancerogenesis. An increase in CIP2A expression has been observed in numerous solid tumors and hematologic malignancies, including multiple myeloma (MM). The aim of our study was to evaluate the clinical impact of the functional single nucleotide polymorphisms (SNP) of the gene (rs2278911, 686C > T) in MM patients.
The study group consisted of 128 patients with de novo MM. EDTA venous blood samples were collected prior to the treatment. The SNPs were analyzed by Real-Time PCR with the use of specific Taqman probes.
Multivariable analysis revealed that variables independently associated with shorter progression-free survival (PFS) included thrombocytopenia, and translocation and the TT genotype of the gene (686C > T) (median PFS: 6 vs. 25 months; HR = 7.18). On the other hand, autologous haematopoietic stem cell transplantation (AHSCT) was related to a lower risk of early disease progression. Moreover, light chain disease, International Staging System (ISS) 3, poor performance status, hypoalbuminemia, translocation and the TT genotype of the gene (686C > T) were independent prognostic factors associated with shorter overall survival (OS) (median OS: 8 vs. 45 months; HR = 7.08).
The evaluation of the SNP 686C > T of the gene could be used as a diagnostic tool in MM patients at risk of early disease progression and death.
该基因编码一种癌蛋白 CIP2A，它可以抑制 Akt 激酶 B 的磷酸化，稳定 c-Myc 蛋白，并通过这种方式促进癌症的发生。在许多实体瘤和血液恶性肿瘤中，包括多发性骨髓瘤（MM），都观察到 CIP2A 表达增加。我们的研究目的是评估该基因（rs2278911，686C > T）功能单核苷酸多态性（SNP）在 MM 患者中的临床影响。
研究组包括 128 例初治 MM 患者。在治疗前采集 EDTA 静脉血样本。采用特定 Taqman 探针的实时 PCR 分析 SNP。
多变量分析显示，与较短无进展生存期（PFS）独立相关的变量包括血小板减少、和易位以及该基因（686C > T）的 TT 基因型（中位 PFS：6 与 25 个月；HR = 7.18）。另一方面，自体造血干细胞移植（AHSCT）与早期疾病进展的风险降低相关。此外，轻链疾病、国际分期系统（ISS）3、不良表现状态、低白蛋白血症、易位和该基因（686C > T）的 TT 基因型是与较短总生存期（OS）相关的独立预后因素（中位 OS：8 与 45 个月；HR = 7.08）。
评估该基因的 SNP 686C > T 可作为 MM 患者早期疾病进展和死亡风险的诊断工具。
