Hao Yuan, Yu Yingyan, Wang Lishun, Yan Min, Ji Jun, Qu Ying, Zhang Jun, Liu Bingya, Zhu Zhenggang
Department of Surgery of Ruijin Hospital, Shanghai Institute of Digestive Surgery, Shanghai Jiaotong University, 197 Ruijin second Road, Shanghai, 200025, P.R. China.
J Proteome Res. 2008 Sep;7(9):3668-77. doi: 10.1021/pr700638k. Epub 2008 Aug 5.
Gastric cancer is one of the most common malignancies in China. So far, there are few reliable serum biomarkers for diagnosis. The available biomarkers of CEA, CA19-9 and CA72-4 are not sufficiently sensitive and specific for gastric cancer. In this study, a high density antibody microarray was used for identifying new biomarkers from serum samples of gastric cancer. Serum samples from colorectal cancer, pancreatic cancer, hepatocellular cancer, and breast cancer were also screened for comparative study. As result, some candidate biomarkers were identified. IPO-38, an up-regulated serum protein in gastric cancer was selected for subsequent validation including serum IPO-38 expression by ELISA and IPO-38 protein expression by immunohistochemistry. The immunoprecipitation by IPO-38 for gastric cancer cell line and MALDI-TOF/TOF mass spectrometer suggested that pull-down of IPO-38 belongs to H2B histone, which was supported by co-localization study of laser scanning confocal microscope. A follow-up study showed that the survival rate of IPO-38 negative group was better than that in IPO-38 positive group. The study first clarified the property of IPO-38 proliferating marker, and proposed that IPO-38 protein is a promising biomarker both for diagnosis and for predicting prognosis of gastric cancer.
胃癌是中国最常见的恶性肿瘤之一。到目前为止,用于诊断的可靠血清生物标志物很少。现有的癌胚抗原(CEA)、糖类抗原19-9(CA19-9)和糖类抗原72-4(CA72-4)生物标志物对胃癌的敏感性和特异性不足。在本研究中,高密度抗体微阵列用于从胃癌血清样本中鉴定新的生物标志物。还对来自结直肠癌、胰腺癌、肝细胞癌和乳腺癌的血清样本进行了筛查以作比较研究。结果,鉴定出了一些候选生物标志物。选择了一种在胃癌中上调的血清蛋白IPO-38进行后续验证,包括通过酶联免疫吸附测定(ELISA)检测血清IPO-38表达以及通过免疫组织化学检测IPO-38蛋白表达。用IPO-38对胃癌细胞系进行免疫沉淀并结合基质辅助激光解吸电离飞行时间串联质谱仪(MALDI-TOF/TOF)分析表明,IPO-38下拉的蛋白属于H2B组蛋白,激光扫描共聚焦显微镜的共定位研究支持了这一结果。一项随访研究表明,IPO-38阴性组的生存率优于IPO-38阳性组。该研究首次阐明了IPO-38增殖标志物的特性,并提出IPO-38蛋白是一种有前景的胃癌诊断和预后预测生物标志物。