鼻咽癌高癌家系外周单个核细胞蛋白质组学研究

摘要

Objective To look for reliable peripheral blood biomarkers for early diagnosis, treatment, mecha-nism of cancerization and evaluation of nasopharyngeal carcinoma (NPC) from familial nasopharyngeal carcinoma. Methods The proteins of peripheral blood mononuclear cells (PBMC) in nasopharyngeal carcinoma (NPC) from famil-ial nasopharyngeal carcinoma, health members of familial nasopharyngeal carcinoma or healthy adults groups were sepa-rated by two-dimensional gel electrophoresis (2DGE), respectively. Then gels were stained by blue silver, scanned by Im-ageScanner and analyzed with PDQuest software. Relative abundance of the protein spots between familial nasopharyn-geal carcinoma and health members of familial nasopharyngeal carcinoma groups, and between health members of famil-ial nasopharyngeal carcinoma or healthy adults groups were calculated by comparing spots density volume on the gel. The differentially expressed protein spots were identified by peptide mass fingerprint (PMF) based on matrix-assisted la-ser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and database searching. Results Well-re-solved and reproducible 2DGE maps of PBMC from patients with NPC from familial nasopharyngal carcinoma, health members of familial nasopharyngeal carcinoma or healthy adults were acquired. Nineteen more than 2 folds differentially expressed protein spots were identified. Some of these proteins participated protein synthesis and degradation, or chaper-one, or protection and detoxification, or cytoskeleton, while some of those were involved in metabolism or signal transduc-tion. Conclusion Through comparative proteomic analysis of PBMC in patients with NPC from familial nasopharyngal carcinoma, health members of familial nasopharyngeal carcinoma or healthy adults, 19 aging related colonic epithelial pro-teins were identified. HSP27, Protein S100-A9, Prohibitin may become reliable peripheral blood biomarkers for early di-agnosis, treatment, mechanism of cancerization and evaluation of NPC from familial nasopharyngeal carcinoma prognosis.%目的：寻找鼻咽癌高癌家系鼻咽癌的癌变机制、早期诊断、治疗和预后监测的外周血特异性分子标志物。方法利用双向凝胶电泳技术(2-DE)分别分离鼻咽癌高癌家系鼻咽癌患者、鼻咽癌高癌家系成员及健康对照组外周血单个核细胞的总蛋白，经蓝银染色后进行图像分析，并对差异表达的蛋白质点进行识别，利用基质辅助激光解吸电离飞行时间质谱得到肽质量指纹图谱，搜索数据库鉴定部分差异蛋白质点。结果建立了鼻咽癌高癌家系鼻咽癌患者、鼻咽癌高癌家系成员及健康对照组外周血单个核细胞的2-DE图谱；发现并鉴定了鼻咽癌高癌家系鼻咽癌患者、鼻咽癌高癌家系成员及健康对照组之间的差异表达大于2倍的蛋白质点19个，这些差异蛋白质点主要为蛋白质合成与分解、抗氧化应激、分子伴侣、细胞结构相关蛋白质、三大代谢相关酶类以及信号传导相关蛋白质等。结论通过对鼻咽癌高癌家系鼻咽癌患者、鼻咽癌高癌家系成员及健康对照组外周血单个核细胞的比较蛋白质学研究，筛选并鉴定到19个与鼻咽癌高癌家系鼻咽癌发生相关的蛋白质，其中HSP27、Protein S100-A9、Prohibitin可能成为鼻咽癌高癌家系鼻咽癌癌变机制、早期诊断、治疗及预后监测的外周血特异性分子标志物。