Fibrinogen γ overexpression in pancreatic cancer identified by large-scale proteomic analysis of serum samples
Fibrinogen γ overexpression in pancreatic cancer identified by large-scale proteomic analysis of serum samples
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DOI：
10.1158/0008-5472.can-05-3659
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发表时间：
2006-03-01
期刊：
影响因子：
11.2
通讯作者：
Yeatman, TJ
中科院分区：
文献类型：
--
作者：
Bloomston, M;Zhou, JX;Yeatman, TJ
胰腺癌的血清标志物的检测一直是难以捉摸的。虽然CA 19-9是最常用的，但其敏感性和特异性是适度的。我们使用大规模蛋白质组学来鉴定胰腺癌的潜在血清标志物。使用高分辨率二维凝胶电泳分析样品，以确定差异表达的蛋白质在32例正常和30例胰腺癌患者。每份血清样品最多可分辨1，744个蛋白质斑点。使用质谱法鉴定候选蛋白质。ANOVA用于鉴定可以区分癌症与正常血清的蛋白质。血清纤维蛋白原水平也采用酶法测定。采用免疫组化法检测胰腺癌组织中纤维蛋白原的表达。154种蛋白质在所有胰腺癌中普遍过表达。九个蛋白质点（四个通过质谱鉴定）可以使用交叉验证有效地将癌症与正常对照分开。这些蛋白质成功区分了所有胰腺癌样本（30/30）和94%的正常样本（30/32）。在这些候选者中突出的是纤维蛋白原γ，随后通过酶分析证实其在胰腺癌血清中过表达（54.1 +/- 64.1对0.0 +/- 0.0 mg/dL，P < 0.05），并且通过免疫组织化学证实其在组织中相对于正常胰腺过表达（67%对29%，P < 0.05）。结合双向凝胶电泳和质谱的蛋白质组学分析成功地鉴定了154种胰腺癌的潜在血清标志物。其中，纤维蛋白原γ，一种与胰腺癌高凝状态相关的蛋白质，将癌症与正常血清区分开来。纤维蛋白原是胰腺癌潜在的肿瘤标志物。
Detection of serum markers for pancreatic cancer has been elusive. Although CA 19-9 is most commonly used, its sensitivity and specificity are modest. We used large-scale proteomics to identify potential serum markers for pancreatic cancer. Samples were analyzed using high-resolution two-dimensional gel electrophoresis to identify differentially expressed proteins in 32 normal and 30 pancreatic cancer patients. Up to 1,744 protein spots were resolved for each serum sample. Candidate proteins were identified using mass spectrometry. ANOVA was used to identify proteins that could discriminate cancer from normal sera. Serum fibrinogen level was also measured using enzymatic assay. Immunohistochemistry was used to detect fibrinogen in resected pancreatic cancers. One hundred fifty-four proteins were commonly overexpressed in all pancreatic cancers. Nine protein spots (four with identifications by mass spectrometry) could effectively separate cancer from normal controls using cross-validation. These proteins successfully discriminated all pancreatic cancer samples (30 of 30) and 94% of normal (30 of 32) samples. Prominent among these candidates was fibrinogen gamma, which was subsequently confirmed to be overexpressed in pancreatic cancer sera by enzymatic analysis (54.1 +/- 64.1 versus 0.0 +/- 0.0 mg/dL, P < 0.05) and tissue by immunohistochemistry (67% versus 29%, P < 0.05) relative to normal pancreas. Proteomic analysis combining two-dimensional gel electrophoresis and mass spectrometry successfully identified 154 potential serum markers for pancreatic cancer. Of these, fibrinogen gamma, a protein associated with the hypercoagulable state of pancreatic cancer, discriminated cancer from normal sera. Fibrinogen is a potential tumor marker in pancreatic cancer.