高发区早期贲门癌及癌前病变蛋白质组学中的应用研究

Application of Proteomics in Early Gastric Cardiac Cancer and Precancerous Lesions in the High Incidence Area

目的应用MALDI-TOF-MS技术检测高发区贲门癌前病变及早癌血清中相关差异蛋白,并利用ExPasy数据库检索相关差异蛋白峰,探讨差异蛋白峰与在肿瘤发生相关性。方法收集来自高发区经病理证实的血清标本259例,其中53例LGIN组,89例HGIN组,60例IGCA组和57例NOR组,采用弱阳离子交换纳米磁珠对血清蛋白进行纯化,MALDI-TOF-MS质谱进行检测。结果三组病变组与NOR组比较以及各组间比较,有统计学差异蛋白峰193个,其中由15个差异蛋白峰1025、1190、1212、1315、1547、1561、1612、3452、3518、4485、5527、7992、8712、14063、33313建立的诊断模型为最优诊断模型。该模型对贲门癌前病变及癌的特异性为100.00%,LGIN的灵敏度100.00%,HGIN的灵敏度85.25%,IGCA的灵敏度93.94%。结论采用MALDI-TOF-MS联合WCX建立诊断模型能够有效区分各组病变,对高发区自然人群初筛工作有一定的应用临床价值。推测贲门癌的发生起始于LGIN或更早,但并不是所有的LGIN均发生癌变。对于表达与肿瘤相关差异蛋白峰的个体,需要给予内镜等干预措施。质谱技术为高发区早期癌及癌前病变初筛及肿瘤发生学研究提供一条新的思路。

Objective MALDI-TOF-MS technique was used to detect the relevant differentially expressed proteins in the serum of precardia and early cancer in high incidence areas,and ExPasy database was used to search the related differentially expressed protein peaks to explore the correlation between differentially expressed protein peaks and tumorgenesis.Methods259pathologically confirmed serum samples were collected from the high-incidence areas,including53LGIN group,89HGIN group,60IGCA group and57NOR group.Serum proteins were purified by weak-cation exchange nano-magnetic beads and detected by MALDI-TOF-MS mass spectrometry.Results There were193statistically significant differentially expressed protein peaks in the pathological changes group,NOR group and each group,among which the optimal diagnostic model was established by15differentially expressed protein peaks:1025,1190,1212,1315,1547,1561,1612,3452,3518,4485,5527,7992,8712,14063and33313.The specificity of this model for precancerous lesions and cancers of cardia was100.00%,the sensitivity of LGIN was100.00%,the sensitivity of HGIN was85.25%,and the sensitivity of IGCA was93.94%.Conclusion MALDI-TOF-MS combined with WCX in the establishment of a diagnostic model can effectively distinguish between the groups of lesions,and has certain clinical value for the screening of natural population in high incidence areas.It is speculated that the occurrence of cardia cancer begins at LGIN or earlier,but not all LGIN cancers occur.Endoscopic and other interventions should be given to individuals expressing differentially expressed tumor-related protein peaks.Mass spectrometry provides a new idea for the early screening and tumorigenesis of early and precancerous lesions in high incidence areas.