Pfetin as a prognostic biomarker of gastrointestinal stromal tumors revealed by proteomics
Pfetin as a prognostic biomarker of gastrointestinal stromal tumors revealed by proteomics
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DOI：
10.1158/1078-0432.ccr-07-1478
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发表时间：
2008-03-15
影响因子：
11.5
通讯作者：
Hirohashi, Setsuo
中科院分区：
文献类型：
--
作者：
Suehara, Yoshiyuki;Kondo, Tadashi;Hirohashi, Setsuo
目的：我们旨在使用蛋白质组学方法开发胃肠道间质瘤 (GIST) 的预后生物标志物。实验设计：我们使用二维差异凝胶电泳检查了 GISTS 的蛋白质组谱。使用大规模样本集和特异性抗体检查了候选生物标志物的预后性能。结果：我们鉴定了 43 个蛋白点，其强度在预后良好和不良的 GISTS 之间存在统计学差异。质谱蛋白质鉴定表明，43 个点对应于 25 个不同的基因产物。 43 个点中的 8 个来自 pfetin（一种钾通道蛋白），并且 8 个 pfetin 点中的 4 个在两组之间具有较高的区分能力。 Western blotting和实时PCR显示pfetin表达与肿瘤转移呈负相关。还通过免疫组织化学对 210 例 GIST 病例检查了 pfetin 的预后表现。 pfetin阳性和pfetin阴性肿瘤患者的5年无转移生存率分别为93.9%和36.2%（P < 0.0001）。单变量和多变量分析显示，pfetin 表达是所检查的临床病理变量中的一个强大的预后因素，包括风险分类和 c-kit 或血小板衍生生长因子受体 A 突变状态。结论：这些结果表明 pfetin 是 GISTS 的强大预后标志物，并可能为预防 GIST 转移提供新的治疗策略。
Purpose: We aimed to develop prognostic biomarkers for gastrointestinal stromal tumors (GIST) using a proteomic approach.Experimental Design: We examined the proteomic profile of GISTS using two-dimensional difference gel electrophoresis. The prognostic performance of biomarker candidates was examined Using a large-scale sample set and specific antibodies.Results: We identified 43 protein spots whose intensity was statistically different between GISTS with good and poor prognosis. Mass spectrometric protein identification showed that the 43 spots corresponded to 25 distinct gene products. Eight of the 43 spots derived from pfetin, a potassium channel protein, and four of the eight pfetin spots had a high discriminative power between the two groups. Western blotting and real-time PCR showed that pfetin expression and tumor metastasis were inversely related. The prognostic performance of pfetin was also examined by immunohistochemistry on 210 GIST cases. The 5-year metastasis-free survival rate was 93.9% and 36.2% for patients with pfetin-positive and pfetin-negative tumors, respectively (P < 0.0001). Univariate and multivariate analyses revealed that pfetin expression was a powerful prognostic factor among the clinicopathologic variables examined, including risk classification and c-kit - or platelet-derived growth factor receptor A mutation status.Conclusions: These results establish pfetin as a powerful prognostic marker for GISTS and may provide novel therapeutic strategies to prevent metastasis of GIST.