Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Room JF-215C, Boston, MA 02115, USA.
Br J Cancer. 2010 Sep 28;103(7):1025-33. doi: 10.1038/sj.bjc.6605846. Epub 2010 Aug 31.
AMP-activated protein kinase (AMPK, PRKA) has central roles in cellular metabolic sensing and energy balance homeostasis, and interacts with various pathways (e.g., TP53 (p53), FASN, MTOR and MAPK3/1 (ERK)). AMP-activated protein kinase activation is cytotoxic to cancer cells, supporting AMPK as a tumour suppressor and a potential therapeutic target. However, no study has examined its prognostic role in colorectal cancers.
Among 718 colon and rectal cancers, phosphorylated AMPK (p-AMPK) and p-MAPK3/1 expression was detected in 409 and 202 tumours, respectively, by immunohistochemistry. Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for clinical and tumoral features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF and PIK3CA mutations.
Phosphorylated AMPK expression was not associated with survival among all patients. Notably, prognostic effect of p-AMPK significantly differed by p-MAPK3/1 status (P(interaction)=0.0017). Phosphorylated AMPK expression was associated with superior colorectal cancer-specific survival (adjusted HR 0.42; 95% confidence interval (CI), 0.24-0.74) among p-MAPK3/1-positive cases, but not among p-MAPK3/1-negative cases (adjusted HR 1.22; 95% CI: 0.85-1.75).
Phosphorylated AMPK expression in colorectal cancer is associated with superior prognosis among p-MAPK3/1-positive cases, but not among p-MAPK3/1-negative cases, suggesting a possible interaction between the AMPK and MAPK pathways influencing tumour behaviour.
AMP 激活的蛋白激酶（AMPK，PRKA）在细胞代谢感应和能量平衡稳态中具有核心作用，并与各种途径相互作用（例如，TP53（p53）、FASN、MTOR 和 MAPK3/1（ERK））。AMP 激活的蛋白激酶的激活对癌细胞具有细胞毒性，支持 AMPK 作为肿瘤抑制因子和潜在的治疗靶点。然而，尚无研究检查其在结直肠癌中的预后作用。
在 718 例结肠和直肠肿瘤中，通过免疫组织化学检测了 409 例肿瘤中磷酸化 AMPK（p-AMPK）和 202 例肿瘤中磷酸化 MAPK3/1 的表达。使用 Cox 比例风险模型计算死亡率风险比（HR），调整了临床和肿瘤特征，包括微卫星不稳定性、CpG 岛甲基化表型、LINE-1 甲基化以及 KRAS、BRAF 和 PIK3CA 突变。
磷酸化 AMPK 的表达与所有患者的生存无关。值得注意的是，p-AMPK 的预后作用与 p-MAPK3/1 状态显著不同（P（交互）=0.0017）。在 p-MAPK3/1 阳性病例中，磷酸化 AMPK 的表达与结直肠癌特异性生存的改善相关（调整 HR 0.42；95%置信区间（CI），0.24-0.74），但在 p-MAPK3/1 阴性病例中则没有（调整 HR 1.22；95% CI：0.85-1.75）。
结直肠癌中磷酸化 AMPK 的表达与 p-MAPK3/1 阳性病例的预后改善相关，但与 p-MAPK3/1 阴性病例无关，这表明 AMPK 和 MAPK 途径之间的可能相互作用影响肿瘤行为。
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