高發區早期賁門癌及癌前病變蛋白質組學中的應用研究

陳仙梅 郭碩 袁麗

摘 要：目的 應用MALDI-TOF-MS技術檢測高發區賁門癌前病變及早癌血清中相關差異蛋白，并利用ExPasy數據庫檢索相關差異蛋白峰，探討差異蛋白峰與在腫瘤發生相關性。方法 收集來自高發區經病理證實的血清標本259例，其中53例LGIN組，89例HGIN組，60例IGCA組和57例NOR組，采用弱陽離子交換納米磁珠對血清蛋白進行純化，MALDI-TOF-MS質譜進行檢測。結果 三組病變組與NOR組比較以及各組間比較，有統計學差異蛋白峰193個，其中由15個差異蛋白峰1025、1190、1212、1315、1547、1561、1612、3452、3518、4485、5527、7992、8712、14063、33313建立的診斷模型為最優診斷模型。該模型對賁門癌前病變及癌的特異性為100.00%，LGIN的靈敏度100.00%，HGIN的靈敏度85.25%，IGCA的靈敏度93.94%。結論 采用MALDI-TOF-MS聯合WCX建立診斷模型能夠有效區分各組病變，對高發區自然人群初篩工作有一定的應用臨床價值。推測賁門癌的發生起始于LGIN或更早，但并不是所有的LGIN均發生癌變。對于表達與腫瘤相關差異蛋白峰的個體，需要給予內鏡等干預措施。質譜技術為高發區早期癌及癌前病變初篩及腫瘤發生學研究提供一條新的思路。

關鍵詞：賁門癌；癌前病變；MALDI-TOF-MS；蛋白質組學

中圖分類號：R735 文獻標識碼：A DOI：10.3969/j.issn.1006-1959.2018.23.020

文章編號：1006-1959（2018）23-0072-04

Abstract：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. Methods 259 pathologically confirmed serum samples were collected from the high-incidence areas， including 53 LGIN group， 89 HGIN group， 60 IGCA group and 57 NOR group. Serum proteins were purified by weak-cation exchange nano-magnetic beads and detected by MALDI-TOF-MS mass spectrometry. Results There were 193 statistically significant differentially expressed protein peaks in the pathological changes group， NOR group and each group， among which the optimal diagnostic model was established by 15 differentially expressed protein peaks： 1025， 1190， 1212， 1315， 1547， 1561， 1612， 3452， 3518， 4485， 5527， 7992， 8712， 14063 and 33313. The specificity of this model for precancerous lesions and cancers of cardia was 100.00%， the sensitivity of LGIN was 100.00%， the sensitivity of HGIN was 85.25%， and the sensitivity of IGCA was 93.94%. 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.

Key words：Cardia cancer；Precancerous lesions；MALDI-TOF-MS；Proteomics

賁門癌（cardia cancer）是常見惡性腫瘤之一，近年來全球遠端胃癌發病呈下降趨勢，但是賁門癌的發病卻不斷上升[1]，目前其檢出方式主要依賴于內鏡檢查，由于屬于侵入性診療方式，而且其對內鏡醫生技術要求較高，難以用于與自然人群大規模普查，所以尋找特異性腫瘤標志物，以縮小內鏡篩查范圍，是目前所要解決的首要問題。而傳統的腫瘤標志物多存在特異性、敏感性低等缺點，難以廣泛應用于臨床，因此，尋找新的特異性腫瘤標志物顯得尤為重要?！?br>