Comprehensive proteome analyses toward biomaker discovery for gastrointestinal and hepatobiliary cancers

为了寻找胃肠道癌症的新生物标志物，研究人员结合ProteinChip系统（SELDI-TOF MS）和荧光2d差异凝胶电泳（2D-DIGE）进行了全面的蛋白质组分析。用琼脂糖2D-DIGE分析原发性食管癌和邻近非癌组织中表达改变的蛋白，并用质谱法鉴定。其中，一种195 kda蛋白periplakin在食管癌中显著下调，免疫印迹证实了这一点。免疫组织化学表明，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。胰腺癌仍然是预后极差的癌症之一。为了寻找一种新的血清生物标志物，我们利用了ProteinChip系统（SELDI-TOF MS）。我们比较了行根治性胰腺切除术的浸润性胰导管癌患者的术前和术后血清资料。我们发现6630Da蛋白在术前血清中比在术后血清中表达更丰富。发现术前血清中该蛋白的高水平提示预后较差。免疫染色显示，6630Da蛋白在胰腺癌细胞中大量表达，而在正常胰腺导管细胞中不表达。习惯性饮酒是多种癌症的一个危险因素。结合SELDI-TOF Ms和2D-DIGE，我们可以检测和鉴定出过量饮酒的几种生物标志物。

In search for novel biomarkers for gastrointestinal cancers, comprehensive proteome analyses were performed combining the ProteinChip system (SELDI-TOF MS) and fluorescent 2-D differential gel electrophoresis (2D-DIGE).Proteins with altered expression in primary esophageal cancer and adjacent non-cancer tissues were analyzed by agarose 2D-DIGE and identified by mass spectrometry. Among them, a 195-kDa protein, periplakin, was significantly downregulated in esophageal cancer, which was confirmed by immunoblotting. Imunohistochemistry 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.Pancreatic cancer still remains one of the cancers with extremely poor prognosis. To find a novel serum biomarkers for this cancer, the ProteinChip system (SELDI-TOF MS) was utilized. We compared pre- and postoperative serum profiles obtained from patients with invasive pancreatic ductal carcinoma who underwent curative pancreatomy. We identified 6630Da protein as more abundantly expressed in preoperative serum than in postoperative serum. It was found that the high preoperative serum levels of this protein suggests poorer prognosis. Immunostaining revealed abundant expression of the 6630Da protein in pancreatic cancer cells, but not in normal pancreatic ductal cells.Habitual alcohol drinking is a risk factor for a variety of cancers. Combining the SELDI-TOF Ms and 2D-DIGE, we could detect and identify several biomarkers for excessive alcohol drinking.