Identification of IMPDH2 as a tumor-associated antigen in colorectal cancer using immunoproteomics analysis
Identification of IMPDH2 as a tumor-associated antigen in colorectal cancer using immunoproteomics analysis
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DOI：
10.1007/s00384-009-0759-2
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发表时间：
2009-11-01
影响因子：
2.8
通讯作者：
Wu, Yuzhang
中科院分区：
文献类型：
--
作者：
He, Yujun;Mou, Zhirong;Wu, Yuzhang
来自癌症患者的血清含有直接针对抗原蛋白的肿瘤特异性自身抗体。肿瘤自身抗原的鉴定可用于癌症的诊断、预后和治疗。在这项研究中，我们使用免疫蛋白质组学分析，以确定肿瘤蛋白质，引起体液反应在结直肠癌（CRC）的CRC细胞系HCT116被用作蛋白质的来源的二维聚丙烯酰胺凝胶电泳和随后的Western印迹分析，其中个体血清中的自身抗体进行了分析。通过基质辅助激光解吸电离飞行时间质谱分析鉴定与癌症患者血清特异性反应的蛋白质。此外，我们还对40例结直肠癌患者的肿瘤组织进行了免疫组化检测，并在25例结直肠癌患者中的8例中检测到了经质谱鉴定的抗肌苷一磷酸脱氢酶II（IMPDH 2）的自身抗体。IMPDH2在结直肠癌组织中的表达明显高于正常对照组，表明免疫蛋白质组学分析在发现肿瘤相关抗原方面具有广阔的应用前景。IMPDH2可能是结直肠癌的一个蛋白质生物标志物和新的治疗靶点。
Sera from cancer patients contain tumor-specific autoantibodies directly against antigenic proteins. The identification of tumor autoantigens may have utility in cancer diagnosis, prognosis, and therapy. In this study, we used immunoproteomics analysis to identify tumor proteins that elicit humoral response in colorectal cancer (CRC).The CRC cell line HCT116 was used as a source of proteins for two-dimensional polyacrylamide gel electrophoresis and subsequent Western blot analysis in which individual serum from patients with CRC was analyzed for autoantibodies. Proteins that specifically react with sera from cancer patients were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis. In addition, the selected protein expression in tumor tissues collected from 40 patients with CRC were assessed by immunohistochemistry.An autoantibody against inosine monophosphate dehydrogenase II (IMPDH2) identified by mass spectrometry was detected in eight out of 25 patients with CRC. However, none of the 15 healthy controls demonstrated autoantibody to IMPDH2.The expression of IMPDH2 in tumor tissue was significantly higher in patients with CRC than that in healthy subjects.The result confirmed that the immunoproteomics analysis holds considerable promise for the discovery of tumor-associated antigens. IMPDH2 may be a protein biomarker and novel therapeutic target in CRC.