Department of Gastroenterological Surgery, Surgical Oncology Laboratory, Peking University People's Hospital, Beijing 100044, PR China.
Int J Oncol. 2011 Feb;38(2):375-83. doi: 10.3892/ijo.2010.873. Epub 2010 Dec 15.
Gastric cancer (GC) is the one of the most common types of cancer in Asia. To better understand the molecular mechanisms underlying GC, and to seek new markers of tumor progression, we used a proteomics strategy to analyze the protein expression patterns in matched pairs of GC tissue and normal gastric mucosa of 8 GC patients. Comparative proteomic analysis, using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), revealed that 32 protein spots showed a >2-fold difference in intensity between tumor and normal tissues. Twenty-six proteins were up-regulated and 6 proteins were down-regulated in tumor tissue compared to control. Western blot analysis confirmed differential expression for 9 proteins, including AGR2, ENO1, GDI2, GRP78, GRP94, PPIA, PRDX1, PTEN and VDAC1. Immunohistochemical staining of a tissue microarray, derived from 145 GC patients, with antibodies for each of the 9 proteins demonstrated a significant association between the level of protein immunostaining and the clinical features of the disease in the donor. The identified proteins were functionally classified using bioinformatics methods, showing that the 9 proteins identified were related to BCL2, BAX, ERBB2 and CASP3 proteins and involved in the process of apoptosis. These proteomic data provide potentially valuable insights into both the biology of GC and the identity of biomarkers for tumor progression. We propose ENO1, GRP78, GRP94, PPIA, PRDX1 and PTEN as potential GC biomarkers.
胃癌（GC）是亚洲最常见的癌症类型之一。为了更好地了解 GC 的分子机制，并寻找肿瘤进展的新标志物，我们使用蛋白质组学策略分析了 8 名 GC 患者配对的肿瘤组织和正常胃黏膜中的蛋白质表达模式。使用二维凝胶电泳（2-DE）和基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）进行比较蛋白质组学分析，显示 32 个蛋白质斑点在肿瘤和正常组织之间的强度差异超过 2 倍。与对照相比，肿瘤组织中有 26 个蛋白上调，6 个蛋白下调。Western blot 分析证实了 9 种蛋白质的差异表达，包括 AGR2、ENO1、GDI2、GRP78、GRP94、PPIA、PRDX1、PTEN 和 VDAC1。用针对这 9 种蛋白质的抗体对来自 145 名 GC 患者的组织微阵列进行免疫组织化学染色，Western blot 分析证实了 9 种蛋白质的差异表达，包括 AGR2、ENO1、GDI2、GRP78、GRP94、PPIA、PRDX1、PTEN 和 VDAC1。用针对这 9 种蛋白质的抗体对来自 145 名 GC 患者的组织微阵列进行免疫组织化学染色，结果表明，在供体中，蛋白质免疫染色水平与疾病的临床特征之间存在显著关联。使用生物信息学方法对鉴定的蛋白质进行功能分类，结果表明，鉴定的 9 种蛋白质与 BCL2、BAX、ERBB2 和 CASP3 蛋白有关，参与细胞凋亡过程。这些蛋白质组学数据为 GC 的生物学和肿瘤进展的生物标志物的鉴定提供了有价值的见解。我们提出 ENO1、GRP78、GRP94、PPIA、PRDX1 和 PTEN 作为潜在的 GC 标志物。
