Wang Xiaoting, Lin Youdong, Lan Fenghua, Yu Yinghao, Ouyang Xuenong, Wang Xuzhou, Huang Qiaojia, Wang Lie, Tan Jianming, Zheng Feng
Department of Experimental Medicine, Fuzhou General Hospital (Dongfang Hospital), Clinical College of Fujian Medical University, 156 North Xi-er Huan Road, Fuzhou, 350025, Fujian, China.
J Cancer Res Clin Oncol. 2014 Aug;140(8):1399-411. doi: 10.1007/s00432-014-1663-x. Epub 2014 Apr 16.
v-akt Murine thymoma viral oncogene homolog (AKT) pathway is critically involved in cancer cell growth, invasion, and survival. We examined the correlation between the genetic variations in molecules of AKT pathway and clinical outcomes of gastric cancer.
Six single nucleotide polymorphisms (SNPs) located in the four core genes of AKT pathway, namely the PIK3CA, PTEN, AKT1, and mTOR, were determined in 221 patients with stage T2 and T3 gastric cancer. Additionally, the activation of AKT1 in gastric cancer tissues was examined by immunostaining. The correlation between SNPs, AKT activation, and the progress of gastric cancer was analyzed after an average of 51-month follow-up.
The overall recurrence and survival rate in this study group were 54.8 and 46.6 %, respectively. The recurrence rate was reduced 30.4 %, and the survival rate was increased 33.7 % in patients with GG allele of a 3'-side AKT1 SNP (rs2498804). Significantly, GG allele was associated with lower AKT1 activation in gastric cancer tissues. On the contrary, CC allele of PTEN (rs701848) was associated with the increased risk of recurrence (hazard ratio [HR] 2.06, 95 % CI 1.19-3.58) and patient death (HR 2.01, 95 % CI 1.15-3.53).
The genetic variants in the PI3K/PTEN/AKT especially the GG allele in 3' side of AKT1 are closely related to clinical outcomes of gastric cancer.
v-akt小鼠胸腺瘤病毒癌基因同源物（AKT）通路在癌细胞的生长、侵袭和存活中起关键作用。我们研究了AKT通路分子的基因变异与胃癌临床结局之间的相关性。
在221例T2和T3期胃癌患者中，检测了位于AKT通路四个核心基因（即PIK3CA、PTEN、AKT1和mTOR）中的六个单核苷酸多态性（SNP）。此外，通过免疫染色检测胃癌组织中AKT1的激活情况。在平均随访51个月后，分析SNP、AKT激活与胃癌进展之间的相关性。
该研究组的总复发率和生存率分别为54.8%和46.6%。AKT1 SNP（rs2498804）3'端GG等位基因的患者复发率降低30.4%，生存率提高33.7%。值得注意的是，GG等位基因与胃癌组织中较低的AKT1激活相关。相反，PTEN（rs701848）的CC等位基因与复发风险增加（风险比[HR]2.06，95%可信区间1.19 - 3.58）和患者死亡（HR 2.01，95%可信区间1.15 - 3.53）相关。
PI3K/PTEN/AKT的基因变异，尤其是AKT1 3'端的GG等位基因，与胃癌的临床结局密切相关。
