Prognostic value of RKIP and p-ERK in gastric cancer.
Prognostic value of RKIP and p-ERK in gastric cancer.
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DOI：
10.1186/1756-9966-31-30
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发表时间：
2012-03-31
期刊：
影响因子：
--
通讯作者：
Sugihara K
中科院分区：
文献类型：
--
作者：
Fujimori Y;Inokuchi M;Takagi Y;Kato K;Kojima K;Sugihara K
丝裂原活化蛋白激酶（MAPK）信号通路参与肿瘤发展的几个步骤，并且被认为是设计化疗剂的突出治疗靶点。我们评估了细胞外信号调节激酶（ERK），丝裂原活化蛋白激酶（MEK），ERK的上游调节因子，Raf激酶抑制蛋白（RKIP）的表达，并研究了这些表达与胃癌临床病理特征和预后的相关性。肿瘤样本来自105例接受根治性胃切除术的胃腺癌患者。采用免疫组化方法检测磷酸化ERK（p-ERK）、磷酸化MEK（p-MEK）和RKIP的表达。RKIP、p-MEK和p-ERK的表达分别见于69例（66%）、54例（51%）和64例（61%）肿瘤。RKIP表达与浸润深度（p < 0.001）、淋巴结受累（p = 0.028）和国际癌症控制联盟（UICC）分期（p = 0.007）呈负相关。RKIP表达与显著更长的无复发生存期（RFS）相关（p = 0.0033），而p-MEK则与此无关（p = 0.79）。p-ERK表达患者的RFS略短，但无显著性差异（p = 0.054）。p-ERK阳性和RKIP阴性表达的患者的RFS显著短于其他患者（p < 0.001）。RKIP和p-ERK表达的组合是独立的预后因素（风险比，2.4; 95%置信区间，1.3 - 4.6; p = 0.008）。我们的研究结果表明，RKIP的丢失与肿瘤进展和生存率低有关。RKIP阴性表达联合p-ERK阳性表达是胃癌患者预后不良的独立预测因子。
The mitogen-activated protein kinase (MAPK) signaling pathway participates in several steps of tumour development and is considered a prominent therapeutic target for the design of chemotherapeutic agents. We evaluated the expressions of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MEK), an upstream regulator of ERK, and Raf kinase inhibitor protein (RKIP), and investigated correlations of these expressions with clinicopathological features and outcomes in gastric cancer. Tumour samples were obtained from 105 patients with gastric adenocarcinomas who underwent radical gastrectomy. The expressions of phosphorylated ERK (p-ERK), phosphorylated MEK (p-MEK), and RKIP were analysed by immunohistochemical staining. Expression of RKIP, p-MEK, and p-ERK was found in 69 (66%), 54 (51%), and 64 (61%) of all tumours, respectively. RKIP expression negatively correlated with the depth of invasion (p < 0.001), lymph node involvement (p = 0.028), and Union for International Cancer Control (UICC) stage (p = 0.007). RKIP expression was associated with significantly longer relapse-free survival (RFS) (p = 0.0033), whereas p-MEK was not (p = 0.79). Patients with p-ERK expression had slightly, but not significantly shorter RFS than those without such expression (p = 0.054). Patients with positive p-ERK and negative RKIP expression had significantly shorter RFS than the other patients (p < 0.001). The combination of RKIP and p-ERK expression was an independent prognostic factor (hazard ratio, 2.4; 95% confidence interval, 1.3 - 4.6; p = 0.008). Our results demonstrated that loss of RKIP was associated with tumour progression and poor survival. Negative RKIP expression combined with positive p-ERK expression was an independent predictor of poor outcomes in patients with gastric cancer.
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