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

使用各种蛋白质组学方法进行蛋白质组分析，用于人类实体瘤的早期诊断和治疗

基本信息

批准号：
16390353
负责人：
TOMONAGA Takeshi
金额：
$ 9.22万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

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

十年来，癌症一直是死亡原因最多的疾病。这部分是由于缺乏理想的肿瘤标记物进行早期诊断。因此，开发具有更高灵敏度和特异性的肿瘤标志物是当务之急。蛋白质组学技术的最新进展使得识别各种癌症的新肿瘤标志物成为可能。蛋白质组学方法主要有两种，二维凝胶电泳（2D gel based，2DE）和质谱/质谱（MS/MS based，MS/MS）。通过Western印迹证实了肿瘤中几种蛋白质的过表达。其中，真核翻译起始因子41-1（eIF-4 H）亚型1在大多数肿瘤组织中表达显著增加。此外，还鉴定了脯氨酰-4-羟化酶β亚基（P4 HB）、膜联蛋白A2和磷酸丙糖异构酶1（TPI 1）的翻译后修饰。我们还鉴定了33种蛋白质， ...更多信息采用荧光二维差异凝胶电泳（2D-DIGE）检测原发性食管癌癌组织与癌旁非癌组织之间的表达。一种195 kDa蛋白。periplakin在食管癌中显著下调，这通过免疫印迹证实。免疫组化结果显示，periplakin在正常上皮和不典型增生病变中主要定位于细胞-细胞边界，而在早期癌中periplakin从细胞边界消失，转移到胞浆，在晚期癌中几乎不表达。这些结果表明，periplakin可能是一个有用的标志物，早期食管癌的检测和评估肿瘤的进展。另一方面，表面增强激光解吸电离飞行时间质谱（SELDI-TOF MS）被用来寻找新的血清标志物胰腺癌。蛋白质谱分析确定了85个峰的簇，这些峰在胰腺癌患者的术前和术后血清中差异表达。其中6630和6420 Da峰强度在20例患者术前血清中显著高于术后血清（P<0.002）。序列氨基酸分析鉴定这些蛋白质是载脂蛋白C-1（ApoC-1）及其截短形式。术前血清ApoC-1水平升高与预后不良显著相关。这些数据有力地表明，血清ApoC-1水平是胰腺癌患者有用的预后标志物。少