Association of MTOR and AKT Gene Polymorphisms with Susceptibility and Survival of Gastric Cancer.
Association of MTOR and AKT Gene Polymorphisms with Susceptibility and Survival of Gastric Cancer.
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MTOR和AKT基因多态性与胃癌的敏感性和存活的关联。
DOI：
10.1371/journal.pone.0136447
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yuan Y
中科院分区：
文献类型：
--
作者：
Piao Y;Li Y;Xu Q;Liu JW;Xing CZ;Xie XD;Yuan Y
磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(PKB，AKT)/哺乳动物靶标雷帕霉素(MTOR)信号通路在血管生成和细胞生长、增殖、代谢、迁移、分化和凋亡中起关键作用。该途径关键因子的遗传多样性可能影响蛋白质功能和信号转导，促进疾病的发生和发展。研究表明MTOR rs1064261和AKT rs1130233基因多态性与多种癌症类型的风险和/或预后相关。然而，这种与胃癌(GC)的关系仍不清楚。本研究的目的是探讨MTOR和AKT基因多态性在胃癌风险和预后中的作用。用Sequenom Massarray软件对1842例个体进行MTORrs1064261 T→C和AKTrs1130233 G→A基因分型。采用酶联免疫吸附试验检测血清幽门螺杆菌抗体。免疫组织化学方法检测总的和磷酸化的MTOR和AKT蛋白。MTORrs1064261(TC+CC)和AKTrs1130233(GA+AA)基因与男性胃癌风险增加相关(P=0.049，P=0.030)。在Hp阴性个体中，AKT rs1130233 GA和(GA+AA)基因与萎缩性胃炎的风险增加相关(AG；P=0.012，P=0.024)。值得注意的是，AKT rs1130233(GA+AA)基因在从健康对照组(CON)到AG(P=0.013)和从AG到GC(P=0.049)的疾病进展过程中与H.Pylori存在显著的交互作用。此外，在携带AKT rs1130233变异的个体中，Hp阳性组的AKT(p-AKT)表达水平较高。AKT基因rs1130233与淋巴结转移、饮酒等临床病理参数相关(P<；0.05)。MTOR rs1064261和AKT rs1130233基因多态与男性GC风险增加和H.Pylori阴性个体AG风险增加相关。AKT rs1130233基因与幽门螺杆菌感染之间存在显著的交互作用，在Con→AG→GC疾病进展中。AKT rs1130233基因型影响幽门螺杆菌感染者p-AKT蛋白的表达。
The phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a critical role in angiogenesis and cell growth, proliferation, metabolism, migration, differentiation, and apoptosis. Genetic diversity in key factors of this pathway may influence protein function and signal transduction, contributing to disease initiation and progression. Studies suggest that MTOR rs1064261 and AKT rs1130233 polymorphisms are associated with risk and/or prognosis of multiple cancer types. However, this relationship with gastric cancer (GC) remains unclear. The aim of this study was to investigate the role of MTOR and AKT polymorphisms in the risk and prognosis of GC. The Sequenom MassARRAY platform was used to genotype 1842 individuals for MTOR rs1064261 T→C and AKT rs1130233 G→A polymorphisms. ELISA was used to detect Helicobacter pylori antibodies in serum. Immunohistochemical analysis was used to detect total and phosphorylated MTOR and AKT proteins. The MTOR rs1064261 (TC+CC) genotype and the AKT rs1130233 (GA+AA) genotype were associated with increased risk of GC in men (P = 0.049, P = 0.030). In H. pylori-negative individuals, the AKT rs1130233 GA and (GA+AA) genotypes were related to increased risk of atrophic gastritis (AG; P = 0.012, P = 0.024). Notably, the AKT rs1130233 (GA+AA) genotype demonstrated significant interactions with H. pylori in disease progression from healthy controls (CON) to AG (P = 0.013) and from AG to GC (P = 0.049). Additionally, for individuals with the AKT rs1130233 variant, those in the H. pylori-positive group had higher levels of phosphorylated AKT (p-AKT) expression. The AKT rs1130233 genotype was found to be associated with clinicopathological parameters including lymph node metastasis and alcohol drinking (P<0.05). MTOR rs1064261and AKT rs1130233 polymorphisms were associated with increased GC risk in males and increased AG risk in H. pylori-negative individuals. A significant interaction existed between the AKT rs1130233 genotype and H. pylori infection in CON→AG→GC disease progression. The AKT rs1130233 genotype influenced p-AKT protein expression in H. pylori-infected individuals.