Prognostic significance of AMP-activated protein kinase expression and modifying effect of MAPK3/1 in colorectal cancer.
Prognostic significance of AMP-activated protein kinase expression and modifying effect of MAPK3/1 in colorectal cancer.
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DOI：
10.1038/sj.bjc.6605846
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发表时间：
2010-09-28
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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AMP活化蛋白激酶（AMPK，PRKA）在细胞代谢传感和能量平衡稳态中具有中心作用，并且与各种途径（例如，TP 53（p53）、FASN、MTOR和MAPK 3/1（ERK））。AMP激活的蛋白激酶激活对癌细胞具有细胞毒性，支持AMPK作为肿瘤抑制剂和潜在的治疗靶点。然而，还没有研究探讨其在结直肠癌中的预后作用。在718例结肠癌和直肠癌中，通过免疫组织化学分别在409例和202例肿瘤中检测到磷酸化AMPK（p-AMPK）和p-MAPK 3/1表达。使用考克斯比例风险模型计算死亡风险比（HR），调整临床和肿瘤特征，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PIK 3CA突变。磷酸化AMPK表达与所有患者的生存率无关。值得注意的是，p-AMPK的预后作用与p-MAPK 3/1状态显著不同（P相互作用=0.0017）。在p-MAPK 3/1阳性病例中，磷酸化AMPK表达与上级结直肠癌特异性生存率相关（校正HR 0.42; 95%置信区间（CI）：0.24-0.74），但在p-MAPK 3/1阴性病例中无关（校正HR 1.22; 95% CI：0.85-1.75）。磷酸化AMPK在结直肠癌中的表达与p-MAPK 3/1阳性病例的上级预后相关，但与p-MAPK 3/1阴性病例无关，这表明AMPK和MAPK通路之间可能存在相互作用，影响肿瘤行为。
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 (Pinteraction=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.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
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影响因子：
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影响因子：
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作者：
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