Zulato E, Bergamo F, De Paoli A, Griguolo G, Esposito G, De Salvo G L, Mescoli C, Rugge M, Nardin M, Di Grazia L, Lonardi S, Indraccolo S, Zagonel V
Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto-IRCCS, Via Gattamelata 64, 35138 Padova, Italy.
Medical Oncology 1 Unit, Istituto Oncologico Veneto-IRCCS, Via Gattamelata 64, 35138 Padova, Italy.
Br J Cancer. 2014 Jul 8;111(1):25-32. doi: 10.1038/bjc.2014.274. Epub 2014 Jun 3.
AMP-activated protein kinase (AMPK) has a central role in cellular energy sensing and is activated in preclinical tumour models following anti-vascular endothelial growth factor (VEGF) therapy. The possible predictive or prognostic role of AMPK status in cancer patients treated with anti-VEGF drugs has not been investigated so far.
Expression of components of the AMPK pathway including phosphorylated AMPK (pAMPK), phosphorylated acetyl-Coa carboxylase (pACC) and liver kinase B1 (LKB1) was investigated by immunohistochemistry in 48 colorectal cancers treated with FOLFIRI plus bevacizumab. Correlation between pAMPK and pACC and associations between the AMPK pathway scores and clinico-pathological characteristics were assessed. Overall survival (OS) was estimated through Kaplan-Meier method, whereas hazard ratios were computed to identify prognostic factors.
Fourteen patients (29.2%) were included in the pAMPK-negative group (score ≤5), whereas 34 patients (70.8%) were included in the pAMPK-positive group (score >5). The Spearman's coefficient for the correlation between pAMPK and pACC scores in primary tumour samples was 0.514 (P=0.0002). Low pAMPK levels were associated with worse OS (P-value 0.0002) but not with PFS, whereas low pACC levels were associated both with worse OS and PFS (P-value 0.0007 and 0.01, respectively).
Our findings suggest that high tissue AMPK activation is a prognostic biomarker in this cohort of metastatic colorectal cancer patients.
AMP 活化蛋白激酶（AMPK）在细胞能量感知中起核心作用，在临床前肿瘤模型中，抗血管内皮生长因子（VEGF）治疗后会被激活。迄今为止，尚未研究 AMPK 状态在接受抗 VEGF 药物治疗的癌症患者中可能的预测或预后作用。
通过免疫组织化学研究了 48 例接受 FOLFIRI 加贝伐单抗治疗的结直肠癌中 AMPK 途径成分的表达，包括磷酸化 AMPK（pAMPK）、磷酸化乙酰辅酶 A 羧化酶（pACC）和肝激酶 B1（LKB1）。评估了 pAMPK 与 pACC 之间的相关性以及 AMPK 途径评分与临床病理特征之间的关联。通过 Kaplan-Meier 方法估计总生存期（OS），同时计算风险比以确定预后因素。
14 例患者（29.2%）被纳入 pAMPK 阴性组（评分≤5），而 34 例患者（70.8%）被纳入 pAMPK 阳性组（评分>5）。原发性肿瘤样本中 pAMPK 与 pACC 评分之间的 Spearman 系数为 0.514（P = 0.0002）。低 pAMPK 水平与较差的 OS 相关（P 值 0.0～02），但与无进展生存期（PFS）无关，而低 pACC 水平与较差的 OS 和 PFS 均相关（P 值分别为 0.0007 和 0.01）。
我们的研究结果表明，高组织 AMPK 活化是这组转移性结直肠癌患者的预后生物标志物。
