信号衔接蛋白的表达预示胰腺导管腺癌预后不良。
Expression of signaling adaptor proteins predicts poor prognosis in pancreatic ductal adenocarcinoma.
作者信息
Wang Lili, Lu Junliang, Wu Huanwen, Wang Li, Liang Xiaolong, Liang Zhiyong, Liu Tonghua
机构信息
Molecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
出版信息
Diagn Pathol. 2017 May 30;12(1):42. doi: 10.1186/s13000-017-0633-4.
BACKGROUND
Adaptor proteins bridge the gap between cell surface receptors and their downstream signaling elements. The clinicopathological and prognostic values of adaptor proteins remain poorly understood. The purpose of the present study was to explore the expression and prognostic value of three adaptor proteins: GRB2-associated binding protein 2 (GAB2), CRK-like protein (CRKL) and fibroblast growth factor receptor substrate 2 (FRS2) in pancreatic ductal adenocarcinoma (PDAC).
METHODS
The expression of GAB2, CRKL, and FRS2 in 77 formalin fixed paraffin embedded (FFPE) samples from 77 PDAC patients, along with three paired fresh PDAC and matched normal tissues from 3 PDAC patients was analyzed by immunohistochemistry and western blot, respectively. The association between the expression of the three proteins and the clinicopathological factors of PDAC was assessed by χ test. The correlation between the expression levels of the three proteins was analyzed by Spearman rank correlation analyses; Kaplan-Meier survival analyses were also performed.
RESULTS
IHC was successful in 75, 76, and 77 cases for GAB2, CRKL, and FRS2, respectively. Of which, the positive rate of GAB2, CRKL, and FRS2 protein expression was 40.00% (30/75), 53.95% (41/76) and 35.06% (27/77), respectively. The positive rate of GAB2, CRKL and FRS2 co-expression was 16.88% (13/77). Though there was no association between GAB2 expression, CRKL expression, FRS2 expression, GAB2/CRKL/FRS2 co-expression and the clinicopathological parameters of PDAC, positive correlations were observed between the expressions of the three proteins. Further, univariate survival analysis showed that positive expression of GAB2, CRKL and FRS2 and co-expression of GAB2/CRKL/FRS2 of PDAC predicted poor clinical outcomes, and multivariate survival analysis suggested that positive expression of GAB2 and positive co-expression of GAB2/CRKL/FRS2 were independent prognostic factors for disease-free survival (DFS) and overall survival (OS), respectively.
CONCLUSION
In conclusion, GAB2, CRKL, and FRS2 may be potential prognosticators and therapeutic targets for PDAC patients.
背景
衔接蛋白在细胞表面受体与其下游信号元件之间架起桥梁。衔接蛋白的临床病理及预后价值仍知之甚少。本研究旨在探讨三种衔接蛋白，即GRB2相关结合蛋白2（GAB2）、CRK样蛋白（CRKL）和成纤维细胞生长因子受体底物2（FRS2）在胰腺导管腺癌（PDAC）中的表达及预后价值。
方法
分别采用免疫组织化学和蛋白质印迹法分析77例PDAC患者福尔马林固定石蜡包埋（FFPE）样本中GAB2、CRKL和FRS2的表达，以及3例PDAC患者的三对新鲜PDAC组织和匹配的正常组织中上述蛋白的表达。采用χ检验评估这三种蛋白的表达与PDAC临床病理因素之间的相关性。采用Spearman等级相关分析这三种蛋白表达水平之间的相关性；同时进行Kaplan-Meier生存分析。
结果
免疫组织化学检测GAB2、CRKL和FRS2分别成功检测75例、76例和77例。其中，GAB2、CRKL和FRS2蛋白表达阳性率分别为40.00%（30/75）、53.95%（41/76）和35.06%（27/77）。GAB2、CRKL和FRS2共表达阳性率为16.88%（13/77）。尽管GAB2表达、CRKL表达、FRS2表达、GAB2/CRKL/FRS2共表达与PDAC临床病理参数之间无相关性，但这三种蛋白的表达之间存在正相关。此外，单因素生存分析显示，PDAC中GAB2、CRKL和FRS2的阳性表达以及GAB2/CRKL/FRS2的共表达预示着临床预后不良，多因素生存分析表明，GAB2的阳性表达和GAB2/CRKL/FRS2的阳性共表达分别是无病生存期（DFS）和总生存期（OS）的独立预后因素。
结论
总之，GAB2、CRKL和FRS2可能是PDAC患者潜在的预后指标和治疗靶点。
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