Zheng Zhendong, Zheng Yingjuan, Zhang Meiyan, Wang Jiejun, Yu Guanzhen, Fang Wenzheng
Department of Oncology, Changzheng Hospital, Shanghai, 200070, China.
Department of Oncology, General Hospital of Shenyang Military Region, Shenyang, 110016, Jilin Province, China.
Tumour Biol. 2016 Apr;37(4):4803-11. doi: 10.1007/s13277-015-4193-5. Epub 2015 Oct 31.
Activation of AMP-activated protein kinase (AMPK) suppressed mammalian target of rapamycin (mTOR) pathway, resulting in impaired cancer cell proliferation. Two cohorts (50 and 1072 cases) of patients with resected gastric adenocarcinoma were enrolled in the study. Immunohistochemical staining for p-AMPKa, p-ACC, p-mTOR, p-S6, and p-4EBP1 was performed on the 50-patient cohort. Tissue microarray blocks containing samples from 1072 patients of Chinese ethnicity were used for the immunohistochemical detection of p-AMPKa and p-S6 levels. p-AMPK and p-ACC were frequently inactivated in both cohorts of gastric cancer samples, while p-mTOR, p-S6, and p-4EBP1 were frequently activated in the small cohort of gastric cancer. However, only levels of p-AMPKa and p-S6 were associated with the overall survival of gastric cancer patients. In the larger 1072-patient cohort, downregulation of p-AMPKa and upregulation of p-S6 were associated with tumor progression and were independent predictors of survival after resection of primary gastric cancer. Therefore, reciprocal expression of p-AMPKa and p-S6 may be promising prognostic biomarkers in patients with gastric cancer.
AMP 活化蛋白激酶（AMPK）的激活抑制了雷帕霉素哺乳动物靶点（mTOR）通路，导致癌细胞增殖受损。本研究纳入了两组（分别为50例和1072例）接受胃腺癌切除术的患者。对50例患者的队列进行了p-AMPKa、p-ACC、p-mTOR、p-S6和p-4EBP1的免疫组织化学染色。使用包含1072名中国汉族患者样本的组织微阵列块进行p-AMPKa和p-S6水平的免疫组织化学检测。在两组胃癌样本中，p-AMPK和p-ACC经常失活，而在小部分胃癌队列中，p-mTOR、p-S6和p-4EBP1经常被激活。然而，只有p-AMPKa和p-S6的水平与胃癌患者的总生存期相关。在更大的1072例患者队列中，p-AMPKa的下调和p-S6的上调与肿瘤进展相关，并且是原发性胃癌切除术后生存的独立预测因素。因此，p-AMPKa和p-S6的相互表达可能是胃癌患者有前景的预后生物标志物。
