多发性骨髓瘤组织lncRNA CCAT2、OTUD1的表达及与其临床病理特征和预后的关系

Expression of lncRNA CCAT2 and OTUD1 in multiple myeloma tissue and their relationship with clinicopathological features and prognosis

目的研究多发性骨髓瘤(MM)组织中长链非编码RNA(lncRNA)结肠癌相关转录物2(CCAT2)、卵巢癌结构域蛋白酶1(OTUD1)的表达及其与MM临床病理特征及预后的关系。方法选取2018年4月至2020年4月于该院诊治的MM患者132例(MM组),以同期行骨髓穿刺且无骨髓功能异常的70例非血液病患者为对照组。采用实时荧光定量PCR检测骨髓组织中lncRNA CCAT2及OTUD1 mRNA表达水平。Pearson相关分析MM患者骨髓组织中lncRNA CCAT2与OTUD1 mRNA表达水平的相关性。比较不同临床病理特征MM患者lncRNA CCAT2及OTUD1 mRNA表达差异。Kaplan-Meier曲线分析不同lncRNA CCAT2及OTUD1 mRNA表达MM患者预后差异。Cox回归分析MM患者预后影响因素。结果MM组患者骨髓组织lncRNA CCAT2表达水平为2.31±0.67,高于对照组的0.85±0.24,而OTUD1 mRNA表达水平(1.22±0.37)低于对照组(2.54±0.75),差异均有统计学意义(t=17.624、16.760,均P<0.001)。MM组患者骨髓组织中lncRNA CCAT2表达水平与OTUD1 mRNA表达水平呈明显负相关(r=-0.731,P<0.001)。不同ISS分期、β2-微球蛋白水平的MM患者lncRNA CCAT2及OTUD1 mRNA表达水平比较差异有统计学意义(P<0.001)。lncRNA CCAT2高、低表达组3年总生存率分别为42.19%(27/64)、66.18%(45/68)。OTUD1 mRNA高、低表达组3年总生存率分别为72.31%(47/65)、37.31%(25/67)。lncRNA CCAT2低表达组MM患者3年累积生存率高于lncRNA CCAT2高表达组,差异有统计学意义(Log-Rankχ^(2)=7.151,P=0.007)。OTUD1 mRNA低表达组MM患者3年累积生存率低于OTUD1 mRNA高表达组,差异有统计学意义(Log-Rankχ^(2)=13.667,P<0.001)。ISS分期Ⅲ期、lncRNA CCAT2高表达是影响MM患者预后的危险因素(P<0.001),OTUD1 mRNA高表达是保护因素(P<0.001)。结论MM患者骨髓组织中lncRNA CCAT2表达水平升高,OTUD1表达水平降低,两者与MM不良临床病理特征有关,是影响MM患者预后的独立因素。

Objective To investigate the expression of long non-coding RNA(lncRNA)CCAT2 and ovarian cancer domain-containing protease 1(OTUD1)in multiple myeloma(MM)tissue and their correlation with clinicopathological characteristics and prognosis of MM.Methods A total of 132 patients with MM(MM group)diagnosed and treated in this hospital from April 2018 to April 2020 were selected.Seventy patients with non-hematological disease who underwent bone marrow puncture without abnormal bone marrow function during the same period served as the control group.The real-time fluorescence quantitative PCR was used to detect the expression levels of lncRNA CCAT2 and OTUD1 mRNA in bone marrow tissue.The Pearson correlation was performed to analyze the correlation between lncRNA CCAT2 and OTUD1 mRNA expression in bone marrow tissues.The expression differences of lncRNA CCAT2 and OTUD1 mRNA were compared among the MM patients with different clinical and pathological characteristics.The Kaplan-Meier curve was used to analyze the difference of prognosis among the MM patients with different lncRNA CCAT2 and OTUD1 mRNA expressions.The Cox regression was performed to analyze the factors affecting the prognosis in MM patients.Results The expression level of lncRNA CCAT2 in the bone marrow tissue of the MM group was significantly higher than that of the control group(2.31±0.67 vs.0.85±0.24),while the expression level of OTUD1 mRNA in the MM group was lower than that of the control group(1.22±0.37 vs.2.54±0.75),and the differences were statistically significant(t=17.624,16.760,all P<0.001).The lncRNA CCAT2 expression level in the bone marrow tissue of the MM group had significantly negative correlation with the OTUD1 mRNA expression level(r=-0.731,P<0.001).The lncRNA CCAT2 and OTUD1 mRNA expression levels had statistical differences among the MM patients with different ISS stages andβ2-microglobulin levels(P<0.001).The 3-year overall survival rates of the high and low expression groups of lncRNA CCAT2 were 42.19%(27/64)and 66.18%(45/68),respectively.The 3-year overall survival rates of the high and low expression groups of OTUD1 mRNA were 72.31%(47/65)and 37.31%(25/67)respectively.The 3-year cumulative survival rate of MM patients in the lncRNA CCAT2 low expression group was significantly higher than that in the lncRNA CCAT2 high expression group,and the difference was statistically significant(Log Rankχ^(2)=7.151,P=0.007).The 3-year cumulative survival rate of MM patients in the OTUD1 mRNA low expression group was significantly lower than that in the OTUD1 mRNAhigh expression group(Log Rankχ^(2)=13.667,P<0.001).The ISS stageⅢand lncRNA CCAT2 high expression were the risk factors affecting the prognosis of MM patients(P<0.01),while the OTUD1 mRNA high expression was the protective factor.Conclusion The lncRNA CCAT2 expression level in bone marrow tissue of the MM patients is increased and OTUD1 expression level is decreased,the both are associated with adverse clinical and pathological characteristics of MM and independent factors affecting the prognosis of MM patients.