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机构地区:[1]中国医学科学院血液学研究所血液病医院 实验血液学国家重点实验室,天津300020
出 处:《中华医学杂志》2015年第40期3285-3288,共4页National Medical Journal of China
基 金:国家自然科学基金(81370632、81470336);国际科技合作项目(2010DFB30270、81200395);国家“十二五”科技支撑项目(2014BAl09812)
摘 要:目的 探讨大肿瘤抑制因子(LATS)1、LATS2 mRNA在套细胞淋巴瘤(MCL)中的表达情况及其预后意义.方法 选取2008年1月至2011年4月在中国医学科学院血液学研究所血液病医院淋巴瘤诊疗中心就诊的小B细胞非霍奇金淋巴瘤(B-NHL)患者共36例,其中MCL 16例,慢性淋巴细胞白血病(CLL)11例,脾边缘区淋巴瘤(SMZL)9例;以8名健康供者作为健康对照.采用实时定量RT-PCR方法检测Hippo 途径的效应分子YAP及LATS1、LATS2 mRNA的表达水平.结果B-NHL患者中MCL、CLL、SMZL 的YAP mRNA 的表达水平均显著高于健康对照(对数值:1.97 ± 0.79、1.83 ±0.54、2.12 ±0.42比1.21 ±1.56,均P〈0.05).LATS1、LATS2在MCL患者中的表达与患者是否存在遗传学异常、无进展生存及总生存密切相关,P53缺失阳性组LATS1的表达水平低于P53缺失阴性组(对数值:0.75 ±0.27比1.10 ±0.19,P=0.035),死亡组LATS1的表达水平低于生存组(对数值:0.76 ±0.27比1.15 ±0.17,P=0.026),LATS1高表达水平者,其无进展生存和总生存时间均长于低表达患者[(70.4 ±32.7)比(5.6 ±2.2)个月,P=0.044;(123.8 ±22.0)比(7.7 ±2.2)个月,P=0.017].结论 YAP在B-NHL患者中的表达较健康人为高,表明B-NHL患者特别是MCL患者中,存在Hippo途径的表达异常.LATS1、LATS2 mRNA在MCL患者中的低表达与部分临床预后因素相关,可能是MCL患者预后较差的指标.Objective To investigate the expression level of large tumor suppressor (LATS) 1, LATS2 mRNA and its prognostic value in mantle cell lymphoma (MCL).Methods A total of 36 B-NHL cases (including MCL 16 cases,chronic lymphoblastic leukemia (CLL) 11 cases,splenic marginal zone cell lymphoma(SMZL) 9 cases)and 8 healthy donors were enrolled in this study from January 2008 to April 2011 in our Lymphoma Clinic Center.The mRNA level of Yap (effector of Hippo pathway) and LATS1,LATS2 mRNA were detected by using real-time quantitative PCR.Log expression values of real-time quantitative PCR data were used in this analysis.Results The YAP mRNA expression level in MCL , CLL and SMZL patient were significantly higher than that in health donor (lg:1.97 ±0.79,1.83 ±0.54, 2.12 ±0.42 vs 1.21 ±1.56, all P 〈0.05).The expression level of LATS1, LATS2 mRNA in MCL was significantly correlated with molecular cytogenetic aberrations , progression free survival(PFS)and overall survival (OS).The LATS1 expression level was statistically lower in the group of MCL with delection P 53 than the group of MCL without delection P53(lg:0.75 ±0.27 vs 1.10 ±0.19,P=0.035).And the LATS1 expression level was statistically lower in the death group than the survival group (lg:0.76 ±0.27 vs 1.15 ±0.17, P =0.026).The PFS and OS were significantly longer in the MCL patients with high level of LATS 1 than that of other MCL patients((70.4 ±32.7)vs(5.6 ±2.2)months,P =0.044;(123.8 ±22.0)vs(7.7 ±2.2) months,P =0.017).Conclusions Hippo pathway is dysfunctional in B-NHL, especially in MCL.The reduced expression of LATS 1,LATS2 in MCL patients is associated with progressive disease , and might be an important prognostic factor in MCL.
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