目的对金黄地鼠胰腺癌模型进行差异蛋白质组学研究,探讨胰腺癌的发病机制并寻找胰腺癌相关生物学标志物。方法提取10例金黄地鼠胰腺癌模型癌组织和癌旁组织总蛋白,使用二维聚丙烯酰胺凝胶电泳(2-DE)进行蛋白分离、PDQuest7.0软件分析获得差异蛋白质,进行质谱(MALDI-TOF/TOF MS)鉴定。结果获得12种差异蛋白质:其中5种蛋白质,包括肌动蛋白、α-烯醇(化)酶、膜联蛋白A4(Annexin A4)、角蛋白8、胸腺嘧啶核苷激酶在胰腺癌组织中表达明显上调(〉4倍);另外7种蛋白质,包括蛋白酶体α1亚单位、羧肽酶B1、核糖体蛋白P1、磷脂酶A2、铁蛋白、连接蛋白3、脑磷脂结合蛋白在胰腺癌旁组织中表达明显上调(〉4倍)。结论 Annexin A4、连接蛋白3、α-烯醇(化)酶、羧肽酶B1、核糖体蛋白P1等可能与肿瘤细胞的浸润和转移有关;核糖体蛋白P1、蛋白酶体α1亚单位与肿瘤细胞的蛋白质生物合成及降解异常有关;脑磷脂结合蛋白可能与肿瘤细胞膜的构建和重塑有关;Annexin A4与蛋白酶体α1亚单位可能是胰腺癌诊断与治疗相关的生物学标记物。
Objective To elucidate the pathogenesis of pancreatic cancer and screen specific biological markers associated with pancreatic cancer by differential proteomics analysis on golden hamster pancreatic cancer model.Methods Total proteins extracted from pancreatic cancer tissue and adjacent tissue of 10 golden hamster were subjected to two-dimensional polyacrylamide gel electrophoresis(2-DE) for protein separation.The obtained differential proteins were analyzed by PDQuest 7.0 software and identified by mass spectrometry(MALDI-TOF/TOF MS).Results 12 differential protein were obtained,including 5 up-regulated proteins in pancreatic cancer tissue including actin,α-enolase,Annexin A4,keratin 8,thymidine kinase(〉4 times) and 7 up-regulated proteins in adjacent tissue including proteasome α1 subunit,carboxypeptidase B1,ribosomal protein P1,phospholipase A2,Ferritin,link protein 3,brain phospholipid-binding protein(〉4 times).Conclusion Annexin A4,link protein 3,α-enolase,carboxypeptidase B1,ribosomal protein P1 may be associated with tumor cell invasion and metastasis.Ribosomal protein P1 and proteasome α1 subunit may be related to abnormal biosynthesis and degradation of protein in tumor cells.Brain phospholipid-binding protein may be connected with membrane construction and remodeling of tumor cells.Annexin A4 and proteasome α1 subunit may be the biological markers of pancreatic cancer associated with diagnosis and therapy.