Department of Hematology/Oncology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 807 Hogukno, Buk-gu, Daegu, South Korea.
Cancer Chemother Pharmacol. 2012 Nov;70(5):735-41. doi: 10.1007/s00280-012-1964-1. Epub 2012 Sep 7.
The present study analyzed the expression of phosphorylated AMP-activated protein kinase (pAMPK), Fyn kinase, and pyruvate dehydrogenase kinase-1 (PDK-1) and their impact on the survival of patients with resected gastric cancer who received cisplatin-based adjuvant chemotherapy.
Korean patients with stage II-IV (M0) gastric adenocarcinoma who underwent a gastrectomy with D2 lymph node resection and received a combination regimen of cisplatin and S-1 were enrolled. Immunohistochemistry was carried out to determine the expression of pAMPK, Fyn kinase, and PDK-1 in operative specimens of gastric cancer. The expression was divided into two groups according to the intensity score (negative: 0 or 1+ and positive: 2+ or 3+).
From January 2006 to July 2010, 73 tumor samples obtained from 74 patients were analyzed. Forty patients were included in the pAMPK-positive group, while 33 patients were included in the pAMPK-negative group. Meanwhile, positive Fyn kinase expression was observed in only 10 patients (13.7 %), and there was no or very weak PDK-1 staining. The clinicopathologic characteristics were similar between the two groups according to the expression of pAMPK. With a median follow-up duration of 26.5 months (2.6-73.2), the estimated 3-year relapse-free survival (RFS) and overall survival rates were 55.0 and 78.4 %, respectively. In a multivariate analysis adjusted for age, sex, Lauren classification, and stage, the pAMPK-negative group was significantly associated with improved RFS (Hazard ratio = 0.459, 95 % CI 0.109-0.711, P = 0.043).
A low expression of pAMPK was found to be correlated with better RFS in patients with resected gastric cancer treated with adjuvant cisplatin-based chemotherapy.
本研究分析了磷酸化 AMP 激活蛋白激酶（pAMPK）、Fyn 激酶和丙酮酸脱氢酶激酶-1（PDK-1）的表达及其对接受顺铂为基础的辅助化疗的胃切除术后患者生存的影响。
纳入韩国接受胃切除术加 D2 淋巴结清扫术且接受顺铂联合 S-1 方案治疗的 II-IV 期（M0）胃腺癌患者。对胃癌手术标本进行免疫组织化学检测以确定 pAMPK、Fyn 激酶和 PDK-1 的表达。根据强度评分（阴性：0 或 1+和阳性：2+或 3+）将表达分为两组。
2006 年 1 月至 2010 年 7 月，分析了 74 例患者的 73 个肿瘤样本。40 例患者被纳入 pAMPK 阳性组，33 例患者被纳入 pAMPK 阴性组。同时，仅 10 例（13.7%）患者的 Fyn 激酶表达为阳性，且 PDK-1 染色为阴性或极弱。根据 pAMPK 的表达，两组的临床病理特征相似。中位随访时间为 26.5 个月（2.6-73.2），估计 3 年无复发生存率（RFS）和总生存率分别为 55.0%和 78.4%。在调整年龄、性别、Lauren 分类和分期的多变量分析中，pAMPK 阴性组的 RFS 显著改善（风险比=0.459，95%CI 0.109-0.711，P=0.043）。
在接受顺铂为基础的辅助化疗的胃切除术后患者中，pAMPK 低表达与更好的 RFS 相关。
