LMXlA基因启动子甲基化以及在胃癌发展中的临床意义

目的通过检测胃癌癌旁距离原发灶不同距离组织及胃癌原发灶LMXlA基因启动子区甲基化状态的差异，分析正常胃组织、癌前病变及癌组织中该基因甲基化的动态变化以及LMXlA基因甲基化与胃癌原发灶病理学的关系，探讨LMXlA基因启动子区甲基化在胃癌阶段性发生及进展中的作用及临床意义。方法采用甲基化特异性PCR法（MSP）检测距胃癌癌灶边缘1、3、5cm组织及胃癌原发灶组织中LMXlA基因甲基化状态。结果LMXlA基因启动子区甲基化发生率在胃癌组织及距胃癌灶边缘1、3、5cm组织中分别为46．0％（23／50）、22．O％（11／50）、8．0％（4／50）和4．0％（2／50），从距癌灶边缘5cm胃组织至胃癌原发灶组织中的表达中随距癌灶边缘距离的减少呈上升趋势，原发灶中甲基化阳性率显著高于距原发灶边缘3cm和5cm组织（x^2=15．42，P〈0．05；x^2=12．63，P〈0．01）。LMXlA基因启动子区甲基化发生率在正常胃组织、癌前病变组织及胃癌原发灶中分别为O％（0／25）、16．0％（4／25）和46．O％（23／50），三者之间的差异具有统计学意义（×^2=24．85，P〈0．01）。LMXlA基因甲基化发生率在胃癌患者透浆膜组57．6％（19／33）显著高于未透浆膜组14．8％（4／27）（X^2=16．50，P〈0．05）；在转移淋巴结数大于7枚以上组52．9％（9／17）显著高于小于7枚组37．5％（6／16）（X^2=12．74，P〈0．05）。LMXlA基因甲基化在性别、年龄、不同大体类型、生长方式及分化程度上胃癌患者间差异无统计学意义。结论LMXlA基因启动子区异常甲基化可能与胃癌的临床进展有一定的相关性。

Significance of promotor hypermethylation of LMX1A in gastric cancer

Objective To investigate the significance of promoter hypermethylation of LMX1A gene in phasic carcinogenesis and progression of gastric cancer through detecting the difference of hypermethylation in gastric cancer tissue and the para-carcinoma tissue, and analyzing the dynamic change of hypermethylation of LMX1A from normal gastric tissue, precancerosis tissue to the cancer tissue as well as studying the relationship between hypermethylation of LMX1A and clinico-pathological features of gastric cancer. Methods Fifty patients with gastric cancer were involved in this study. LMX1A methylation states of gastric cancer tissue and the corresponding 1,3,5 cm para-carcinoma tissues were detected by methylation-specific PCR（MSP）. Results Promotor hypermethylation rates of LMX1A gene in gastric cancer tissue and the corresponding 1,3,5 cm para-carcinoma tissues were 46. 0% （23/50） , 22.0% （11/50 ） , 8.0% （4/50）and 4.0% （2/50） respectively, which exhibited a upgrading tendency with the decrease of distance from 5 cm para-eareinoma tissue to the cancer tissue, and the positive rate of methylation in cancer tissue was significantly higher than that in 3,5 em para-earcinoma tissues （ x^2 = 15.42, P 〈 0. 05 ; X2 = 12. 63, P 〈 0.01 ）. Hypermethylation rates of LMX1A gene in normal, precaneerosis and cancer tissue were 0 （0/25） , 16. 0% （4/25）and 46. 0% （23/50）respectively, and the difference was significant among the three groups （X^2 = 24. 85, P 〈 0. 01 ）. Hypermethylation of LMX1A was related to the invasion depth of gastric wall （57. 6% vs. 14. 8; X^2 = 16. 50, P 〈 0. 05）and also the number of lymph nodes involved. No statistical difference of hypermethylation of LMX1A gene was found between different genders, ages, gross types, growthpatterns and differentiation degreess of gastric cancer. Conclusions Promotor hypermethylation of LMX1A gene may be related to the progression of gastric cancer.