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磷酸化Akt过表达与非小细胞肺癌患者发生脑转移的较高风险相关。

Phosphorylated-Akt overexpression is associated with a higher risk of brain metastasis in patients with non-small cell lung cancer.

作者信息

Jin Yu, Yuan Ye, Yi Minxiao, Han Hu, Liu Bo, Li Qianxia

机构信息

Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Department of Clinical Medicine, School of Medicine, Shihezi University, Shihezi, Xinjiang, China.

出版信息

Biochem Biophys Rep. 2019 Mar 25;18:100625. doi: 10.1016/j.bbrep.2019.100625. eCollection 2019 Jul.

Abstract

Brain metastasis (BM) of non-small cell lung cancer (NSCLC) is relatively common and has a poor prognosis. Moreover, identifying which patients are more likely to develop BM is challenging. Akt, a serine/threonine-specific protein kinase, can be activated in various tumors, including lung cancer, and may be associated with poor prognosis. Here, we used immunohistochemistry to evaluate phosphorylated-Akt (p-Akt) expression in tumor tissues of 99 NSCLC patients. We also analyzed the genotype of the patients for two single nucleotide polymorphisms (SNPs) of the gene, rs2498804 and rs2494732. We found that p-Akt expression differs between NSCLC patients and correlates with the risk of BM. Indeed, patients exhibiting medium to high p-Akt expression had a higher incidence of BM than those exhibiting low to no p-Akt expression (39% vs 16%). Our data also show that patients with the rs2498804 GT/GG and rs2494732 CT/TT variant genotypes were more likely to exhibit higher levels of p-Akt expression than those with the rs2498804 TT and rs2494732 CC variant genotypes (35% vs. 24% and 37% vs. 25%, respectively). Our results suggest that the level of expression of p-Akt, which may be affected by the genotype, is correlated with the risk of BM. However, further studies are needed to establish p-Akt as a predictive marker for BM in NSCLC patients.

摘要

非小细胞肺癌(NSCLC)的脑转移(BM)相对常见且预后较差。此外,确定哪些患者更易发生脑转移具有挑战性。Akt是一种丝氨酸/苏氨酸特异性蛋白激酶,可在包括肺癌在内的多种肿瘤中被激活,且可能与预后不良相关。在此,我们采用免疫组化法评估了99例NSCLC患者肿瘤组织中磷酸化Akt(p-Akt)的表达情况。我们还分析了患者该基因两个单核苷酸多态性(SNP),即rs2498804和rs2494732的基因型。我们发现,NSCLC患者中p-Akt表达存在差异,且与脑转移风险相关。实际上,p-Akt表达为中到高水平的患者发生脑转移的发生率高于p-Akt表达为低到无水平的患者(39%对16%)。我们的数据还显示,rs2498804为GT/GG以及rs2494732为CT/TT变异基因型的患者比rs2498804为TT以及rs2494732为CC变异基因型的患者更易表现出较高水平的p-Akt表达(分别为35%对24%以及37%对25%)。我们的结果表明,可能受该基因型影响的p-Akt表达水平与脑转移风险相关。然而,还需要进一步研究以确立p-Akt作为NSCLC患者脑转移的预测标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e442/6444023/9cf47d66bbe6/gr1.jpg

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