Inverse association between Raf Kinase Inhibitory Protein and signal transducers and activators of transcription 3 expression in gastric adenocarcinoma patients: Implications for clinical outcome
Inverse association between Raf Kinase Inhibitory Protein and signal transducers and activators of transcription 3 expression in gastric adenocarcinoma patients: Implications for clinical outcome
复制标题
DOI：
10.1158/1078-0432.ccr-07-4496
复制
发表时间：
2008-05-15
影响因子：
11.5
通讯作者：
Resnick, Murray B.
中科院分区：
文献类型：
--
作者：
Chatterjee, Devasis;Sabo, Edmond;Resnick, Murray B.
目的：Raf激酶抑制蛋白（RKIP）是一种转移抑制蛋白，通过调节化疗药物或免疫刺激诱导的细胞凋亡在肿瘤中起关键作用。转录3信号换能器和激活因子（STAT3）是一种在胃腺癌中经常被激活，从而促进肿瘤生长的转录因子。我们检测了RKIP和STAT3在人类胃癌中的表达模式，预测RKIP状态升高可能有利于临床结果。实验设计：从143例胃腺癌患者的样本中创建组织微阵列。对微阵列进行RKIP和STAT3的免疫组织化学染色，并对染色的强度和程度进行半定量评分。结果：在肠型胃腺癌中，RKIP与STAT3的表达呈负相关。胞质RKIP表达与患者生存直接相关。细胞核STAT3表达与存活呈负相关。在弥漫性肿瘤类型中，RKIP与患者预后无显著相关性。在肠型胃腺癌中，调整治疗类型的多变量分析显示，RKIP和肿瘤分期是生存的重要独立预测因子。在弥漫性肿瘤类型中，分期是唯一有意义的生存预测因子。结论：细胞质RKIP表达在肠亚型胃腺癌中具有预测和保护作用。相反，在肠亚型中，核STAT3表达与患者预后不良相关。值得注意的是，我们发现RKIP与STAT3呈负相关，而RKIP与患者生存呈正相关。
Purpose: Raf Kinase Inhibitory Protein (RKIP) plays a pivotal role in cancer by regulating apoptosis induced by chemotherapeutic agents, or immune-mediated stimuli and is a metastasis suppressor protein. The signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is frequently activated in gastric adenocarcinomas, thereby promoting tumor growth. We examined the expression patterns of RKIP and STAT3 with regard to human gastric cancer, predicting that elevated RKIP status may favor clinical outcome.Experimental Design: Tissue microarrays were created from samples from 143 patients with gastric adenocarcinomas. The microarrays were immunohistochemically stained for RKIP and STAT3, and the intensity and extent of the staining was semiquantitatively scored.Results: In intestinal-type gastric adenocarcinomas, RKIP and STAT3, expression were inversely associated. Cytoplasmic RKIP expression directly correlated with patient survival. Nuclear STAT3 expression inversely correlated with survival. In the diffuse tumor type, no significant correlation was found between RKIP and patient outcome. In the intestinal-type gastric adenocarcinoma, multivariate analysis adjusted for treatment types revealed RKIP and tumor stage to be significant independent predictors of survival. In the diffuse tumor type, stage was the only significant predictor of survival.Conclusion: These results indicate the predictive and protective role of cytoplasmic RKIP expression in gastric adenocarcinoma of the intestinal subtype. In contrast, nuclear STAT3 expression is associated with poor patient prognosis in the intestinal subtype. Significantly, we show an inverse association between RKIP and STAT3 and a positive correlation between RKIP and patient survival.