Molecular Alterations and Expression Dynamics of LATS1 and LATS2 Genes in Non-Small-Cell Lung Carcinoma
Molecular Alterations and Expression Dynamics of LATS1 and LATS2 Genes in Non-Small-Cell Lung Carcinoma
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DOI：
10.1007/s12253-017-0225-3
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发表时间：
2018-04-01
影响因子：
2.8
通讯作者：
Mudassar, Syed
中科院分区：
文献类型：
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作者：
Malik, Showkat A.;Khan, Mosin S.;Mudassar, Syed
大肿瘤抑制因子(LATS)是河马信号通路中的重要成员，可以调节器官大小和细胞增殖。然而，LATS在肺癌中的表达及其临床意义却知之甚少，尤其是在这一地区。我们用甲基化特异性聚合酶链式反应(甲基化特异性聚合酶链式反应)和实时荧光定量聚合酶链式反应(Real-time PCR)研究了69例非小细胞肺癌(NSCLC)患者及其相应的正常肺组织中LATS1和LATS2启动子高甲基化的频率和表达。NSCLC组织中LATS1和LATS1基因启动子甲基化频率分别为66.66%(46/69)和71%(49/69)。55%和66.66%的NSCLC患者LATS1和LATS2基因表达降低。LATS1mRNA在正常肺组织中的表达显著高于正常肺组织。此外，LATS1和LATS2高甲基化的NSCLC组织中的mRNA水平也显著降低。多变量分析证实，在调整了其他临床病理因素后，LATS1表达不足增加了死亡风险。重要的是，LATS1mRNA表达的缺失与总的短生存期有关。LATS1是一个独立的预后因子，可能在NSCLC的进展中发挥重要作用，并可能成为NSCLC的一个新的治疗靶点。
Large tumor suppressor (LATS) is an important member of the Hippo pathway which can regulate organ size and cell proliferation. However, very little is known about the expression and clinical significance of LATS in lung cancer especially from this part of the world. We elucidated the frequency of LATS1 &LATS2 promoter hypermethylation (by methylation-specific PCR) and expression (by real-time PCR) in sixty nine (n = 69) Non-Small Cell Lung Cancer (NSCLC) patients and their corresponding normal lung tissue samples. We found promoter hypermethylation frequencies of LATS1 & LATS1to be 66.66% (46/69) and 71% (49/69) in NSCLC tissues. Decreased LATS1 & LATS2 mRNA expression was found in 55% and 66.66% of NSCLC patients. The LATS1 mRNA expression was significantly higher in normal lung tissues. Also, the mRNA levels of LATS1 and LATS2 NSCLC tissues with hypermethylation were significantly lower. Multivariable analysis confirmed that LATS1 under expression increased the hazard of death after adjusting for other clinicopathological factors. Importantly, the loss of LATS1 mRNA expression was associated with overall short survival. LATS1 is an independent prognostic factor and may play an important role in NSCLC progression and may serve as a novel therapeutic target of NSCLC.