Proteome analysis for early diagnosis and treatment of human solid tumors using various proteomic approaches

十年来，癌症一直是死亡率最高的疾病。这部分是由于缺乏早期诊断的理想肿瘤标志物。因此，开发具有更高敏感性和特异性的肿瘤标志物有待探索。蛋白质组学技术的最新进展使鉴定各种癌症的新肿瘤标志物成为可能。有两种主要的蛋白质组学方法，基于2D凝胶（2DE）和基于MS/MS的方法。在这项研究中，我们鉴定了36个在原发性结直肠癌中表达被2-DE改变的蛋白。Western blotting证实了肿瘤中几种蛋白的过表达。其中，真核翻译起始因子41-1 （eIF-4H）异构体1在大多数肿瘤组织中的表达均显著升高。此外，还鉴定了脯氨酸-4-羟化酶β亚基（P4HB）、膜联蛋白A2和三磷酸异构酶1 （TPI1）的翻译后修饰。我们还利用荧光2D差异凝胶电泳（2D- dige）鉴定了33个蛋白在原发性食管癌的癌组织和邻近非癌组织中表达改变。一个195kDa的蛋白质。免疫印迹证实，Periplakin在食管癌中表达显著下调。免疫组化显示，在正常上皮和发育不良病变中，periplakin主要定位于细胞边界，而在早期癌症中，periplakin从细胞边界消失，转移到细胞质中，在晚期癌症中几乎不表达。提示periplakin可作为早期食管癌检测和肿瘤进展评估的有效标志物。另一方面，表面增强激光解吸电离飞行时间质谱（SELDI-TOF MS）被用于寻找新的胰腺癌血清生物标志物。蛋白谱分析鉴定出85个峰簇，它们在胰腺癌患者术前和术后血清中差异表达。其中，20例患者术前血清中6630、6420 Da的峰值强度水平显著高于术后血清（P<0.002）。序列氨基酸分析鉴定这些蛋白为载脂蛋白C-1 （ApoC-1）及其截短形式。术前血清中ApoC-1水平高与预后不良有显著相关性。这些数据强烈提示血清ApoC-1水平是胰腺癌患者的一个有用的预后指标。少

Cancer has been the disease with the highest cause of death for a decade. This is partly due to the lack of ideal tumor markers for early diagnosis. Therefore, development of tumor markers with higher sensitivity and specificity is waiting to emerge. Recent advances in proteomic technology made it possible to identify novel tumor markers for various cancers. There are two prominent types of proteomic approaches, 2D gel-based (2DE) and MS/MS based approach.In this study, we identified 36 proteins whose expression is altered in primary colorectal cancer by 2-DE. The overexpression of several proteins in tumors was confirmed by Western blotting. Among them, the expression of eukaryotic translation initiation factor 41-1 (eIF-4H) isoform 1 greatly increased in most of the tumor tissues. Moreover, post-translational modifications of the prolyl-4-hydroxylase β subunit (P4HB), annexin A2, and triosephosphate isomerase 1 (TPI1) were also identified. We also identified 33 proteins with altered … More expression between cancer and adjacent non-cancer tissues in primary esophageal cancer using fluorescent 2D differential gel electrophoresis (2D-DIGE). A 195kDa protein. periplakin, was significantly downregulated in esophageal cancer, which was confirmed by immunoblotting. Immunohistochemistry showed that periplakin was mainly localized at cell-cell boundaries in normal epithelium and dysplastic lesions, while it disappeared from cell boundaries, shifted to cytoplasm, in early cancers and scarcely expressed in advanced cancers. These results suggest that periplakin could be a useful marker for detection of early esophageal cancer and evaluation of tumor progression.On the other hand, surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS) was used to find novel serum biomarkers for pancreatic cancer. Protein profiling analysis identified clusters of 85 peaks, which were differentially expressed in the pre- and postoperative sera of pancreatic cancer patients. Among these peaks, the peak intensity levels of 6630 and 6420 Da were significantly higher in the preoperative serum than in the postoperative serum of 20 patients (P<0.002). Sequential amino acid analysis identified these proteins to be apolipoprotein C-1 (ApoC-1) and its truncated form. The high level of ApoC-1 in preoperative serum was significantly correlated with a poor prognosis. These data strongly suggest that the serum ApoC-1 level is a useful prognostic marker in pancreatic cancer patients. Less