β-catenin在多发性骨髓瘤中的表达及其临床意义

Expression and Clinical Significance of β-catenin in Multiple Myeloma

背景与目的:β-catenin是Wnt通路中的关键因子,在细胞粘附和信号转导中发挥着重要作用,目前已在多种人类肿瘤检测到β-catenin的高表达。本研究旨在探讨β-catenin在多发性骨髓瘤(multiplemyeloma,MM)中表达的临床意义。方法:选取26例MM患者(其中初治12例,复发/难治14例)和11例正常人骨髓标本,用逆转录-聚合酶链反应(RT-PCR)和蛋白印迹(Westernblot)法分别检测其β-cateninmRNA和蛋白质水平的表达,比较各组表达水平的差异,结合患者临床特征和疗效进行分析。结果:β-cateninmRNA在正常人、初治组MM患者和难治/复发组MM患者骨髓细胞中阳性率分别为27.3%(3/11)、75.0%(9/12)和100%(14/14),表达水平分别为0.35±0.17、0.72±0.11和0.85±0.16,初治和难治/复发MM患者β-cateninmRNA阳性率和表达水平均显著高于对照组(P<0.01),而难治/复发MM组β-cateninmRNA表达水平高于初治组(P=0.045)。所有的正常标本中均未检测到β-catenin蛋白,在初治MM和难治/复发MM中β-catenin蛋白阳性率分别为50.0%(6/12)和85.7%(12/14),蛋白表达水平分别为0.21±0.08和0.32±0.11,难治/复发MM组明显为高(P=0.039)。10例可评价疗效的初治病例中,无效组β-catenin蛋白阳性率(100%,3/3)明显高于有效组(14.3%,1/7)(P=0.033)。26例患者进行D/S分期,Ⅲ期患者β-catenin蛋白阳性率明显高于Ⅱ期患者,分别为87.5%(14/16)和40.0%(4/10)(P=0.026);进行ISS分期,Ⅲ期患者β-catenin蛋白阳性率(100%,11/11)明显高于Ⅰ期患者(45.5%,5/11)和Ⅱ期患者(33.3%,1/3)(P=0.006和0.032)。18例β-catenin蛋白表达阳性患者,其β-catenin蛋白表达水平与血清β2-微球蛋白水平及血清乳酸脱氢酶水平均呈中度正相关(r分别为0.688和0.502,P值分别为0.002和0.034)。结论:β-catenin蛋白表达与MM的疗效、Durin-Salmon分期和ISS分期有关,并与血清LDH、β2-MG水平呈正相关。

BACKGROUND ＆ OBJECTIVE： β-catenin is the pivotal regulator in Wnt pathway and in charge of cellular adhesion and signal conduction. Overexpression of β-catenin has been observed in various human tumors. This study was to investigate the expression and clinical significance of β-catenin in multiple myeloma （MM）. METHODS： Reverse transcription-polymerase chain reaction （RT-PCR） and Western blot were used to detect mRNA and protein expression of β-catenin in bone marrow samples from 12 newly diagnosed MM patients, 14 relapsed /refractory MM patients, and 11 healthy donors. The clinical data and treatment outcomes of the MM patient were also analyzed. RESULTS： The positive rate and the expression level of β-catenin mRNA were significantly lower in healthy donors than in newly diagnosed patients and relapsed /refractory patients （27.3% vs. 75.0% and 100%, P=5.01e-4; 0.35±0.17 vs. 0.72±0.11 and 0.85±0.16, P =5.88e -5） ; the mRNA level of β-catenin was significantly lower in newly diagnosed patients than in relapsed /refractory patients （P=0.045）. β-catenin protein was not detected in healthy donors; while the positive rate and the expression level of β-catenin protein were significantly lower in newly diagnosed patients than in relapsed /refractory patients （50.0% vs. 85.7%, 0.32±0.11 vs. 0.21±0.08, P=0.039）. In the 10 newly diagnosed MM patients with evaluable treatment outcomes, the positive rate of β-catenin protein was significant lower in the 7 patients without response than in the 3 patients showed response （ 14.3% vs . 100% , P = 0.033 ） . The positive rate of β-catenin protein was significant higher in the 16 Durie /Salmon stage Ⅲ patients than in the 10 stage Ⅱ patients （87.5% vs. 40.0%, P=0.026） , and significant higher in ISS stage Ⅲpatients than in stage Ⅰ and Ⅱ patients （ 100% vs. 45.5% and 33.3% , P=0.006, P=0.032） . The protein level of β-catenin was positively correlated to serum levels of β2-MG （r=0.688, P= 0.002） and lactate dehydrogenase （LDH） （r =0.502, P =0.034）. CONCLUSION： The expression of β-catenin is related with treatment outcome, Durin-Salmon stage and ISS stage of MM, and is positively correlated to serum levels of LDH and β2-MG.