Elevated expression of G3BP1 associates with YB1 and p-AKT and predicts poor prognosis in nonsmall cell lung cancer patients after surgical resection
Elevated expression of G3BP1 associates with YB1 and p-AKT and predicts poor prognosis in nonsmall cell lung cancer patients after surgical resection
复制标题
G3BP1 表达升高与 YB1 和 p-AKT 相关，可预测非小细胞肺癌患者手术切除后的不良预后
DOI：
10.1002/cam4.2579
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发表时间：
2019-09-27
期刊：
影响因子：
4
通讯作者：
Fan, Songqing
中科院分区：
文献类型：
--
作者：
Zheng, Hongmei;Zhan, Yuting;Fan, Songqing
G3BP1是一种rna结合蛋白，在信号通路中起调节作用。YB-1是由YBX1基因编码的DNA/RNA结合蛋白。磷酸化AKT （p-AKT）在PI3K/AKT通路中起关键作用。在不同条件下，YB-1通过激活G3BP1的翻译来驱动应力颗粒（SGs）的形成。SGs参与许多不同的代谢和信号通路，其中可能包括PI3K/AKT/mTOR。在非小细胞肺癌（NSCLC）手术切除患者中，G3BP1、p-AKT和YB1的表达与临床病理特征/预后的关系尚未见报道。方法通过下载TCGA （Cancer Genome Atlas）数据，研究非小细胞肺癌中G3BP1和YB1 (YBX1) mRNA的表达及其相关性。此外，利用免疫组化技术研究了G3BP1、YB1和p-AKT蛋白在非小细胞肺癌组织微阵列和非癌肺组织中的表达。结果我们发现G3BP1和YB1 mRNA在NSCLC组织中表达较高(P。G3BP1与YB1 mRNA水平呈正相关（r = .399, P < .001）。G3BP1、YB1和P - akt蛋白在NSCLC组织中的表达也较高（均P < 0.05）。临床II期、III期患者G3BP1、YB1蛋白表达高于I期患者（P均< 0.05）。G3BP1蛋白表达与YB1、P - akt呈正相关（P < 0.05）。此外，G3BP1、YB1和P - akt蛋白过表达的患者总生存期较短（均P < 0.05）。多因素分析证实，G3BP1蛋白过表达是NSCLC患者预后较差的独立因素（P = 0.039）。结论G3BP1可能在激活PI3K/AKT/mTOR通路中发挥重要作用。G3BP1可能作为手术切除的非小细胞肺癌患者的一种新的预后生物标志物，为非小细胞肺癌的机制和治疗研究提供新的见解。
Purpose G3BP1 is an RNA-binding protein and plays roles in regulating signaling pathway. YB-1 is a DNA/RNA binding protein encoded by YBX1 gene. Phosphorylated AKT (p-AKT) acts as a pivotal molecule in PI3K/AKT pathway. YB-1 drives stress granules (SGs) formation by activating G3BP1 translation under diverse conditions. SGs are involved in many different metabolic and signaling pathways which may include PI3K/AKT/mTOR. So far, there has been no report on the relationship between expression of G3BP1, p-AKT, and YB1 and clinicopathological features/prognosis in surgically resected nonsmall cell lung cancer (NSCLC) patients. Methods In this study, data from TCGA (The Cancer Genome Atlas) were downloaded to investigate the mRNA expression of G3BP1 and YB1 (YBX1) and their correlation in NSCLC. Also, expression of G3BP1, YB1, and p-AKT proteins was studied using immunohistochemistry in tissue microarrays of NSCLC and in noncancerous lung tissues. Results We found that the mRNA expression of G3BP1 and YB1 was higher in NSCLC tissues (both P .05), and G3BP1 was positively correlated with YB1 in mRNA level (r = .399, P < .001). Also, expression of G3BP1, YB1, and p-AKT proteins was higher in NSCLC tissues (all P < .05). And higher expression of G3BP1 and YB1 proteins was seen in patients with clinical stage II and III compared with stage I (both P < .05). Besides, expression of G3BP1 protein had a positive correlation with YB1 and p-AKT (both P < .05). Moreover, overall survival was shorter in patients with overexpression of G3BP1, YB1, and p-AKT proteins (all P < .05). Multivariate analysis confirmed that overexpression of G3BP1 protein was an independent poorer prognostic factor for NSCLC patients (P = .039). Conclusion G3BP1 may play a crucial role in activating PI3K/AKT/mTOR pathway. G3BP1 might be served as a novel prognostic biomarker for surgically resected NSCLC patients, which afforded new insights into the study on the mechanism and therapy of NSCLC.