LRRTM1基因甲基化是胰腺癌的潜在诊断和预后标志物  

LRRTM1 gene methylation is a potential diagnostic and prognostic marker of pancreatic cancer

作　　者：张帆 张美英 高嫒嫒 郭明洲 ZHANG Fan;ZHANG Meiying;GAO Aiai;GUO Mingzhou(Department of Gastroenterology,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003;Department of Gastroenterology&Hepatology,the First Medical Center,Chinese PLA General Hospital,China)

机构地区：[1]新乡医学院第三附属医院消化内科,河南新乡453003 [2]中国人民解放军总医院第一医学中心消化内科医学部

出　　处：《胃肠病学和肝病学杂志》2024年第5期585-589,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家重点研发计划(2020YFC2002705);国家自然科学基金委员会资助项目(82272632,81672318);解放军总医院青年自主创新科学基金项目(22QNCZ027)。

摘　　要：目的探讨LRRTM1基因在胰腺癌中的表观遗传调控机制及其甲基化作为诊断和预后标志物的可能性。方法应用半定量RT-PCR与甲基化特异性PCR(methylation-specific PCR,MSP)技术检测6株胰腺癌细胞系中LRRTM1的表达及启动子区甲基化情况,应用MSP在101例癌前病变样本和277例胰腺癌组织中检测LRRTM1启动子区甲基化情况,并分析LRRTM1甲基化与临床病理因素之间及胰腺癌患者总生存期的关系。结果LRRTM1在Capan1、Panc3.11、AsPC1和PANC-28细胞中缺失表达,其MSP结果为完全甲基化状态,在Capan2和CFpac1中正常表达,MSP结果为未甲基化状态。应用去甲基化药物5-aza-dc处理细胞后,LRRTM1在Capan1、Panc3.11、AsPC1和PANC-28细胞恢复表达,在Capan2和CFpac1细胞中表达未改变。表明LRRTM1基因在胰腺癌中的表达受甲基化调控。在16.83%(17/101)的癌前病变样本和52.35%(145/277)的原发性胰腺癌中,LRRTM1发生甲基化,且LRRTM1甲基化与患者的年龄相关(P<0.05)。在获得随访信息的232例胰腺癌组织样本中发现LRRTM1甲基化与胰腺癌患者总生存期呈负相关。结论LRRTM1基因在胰腺癌组织中频繁发生甲基化,其表达受启动子区甲基化调控,LRRTM1甲基化是胰腺癌潜在的诊断和预后标志物。Objective To investigate the epigenetic regulation of LRRTM1 gene expression and the possibility of LRRTM1 methylation as a diagnostic and prognostic marker.Methods LRRTM1 expression and promoter methylation status in 6 pancreatic cancer cell lines were detected by semi-quantitative RT-PCR and methylation-specific PCR(MSP).MSP was used to detect the methylation status of LRRTM1 in 101 cases of precancerous and 277 cases of pancreatic cancer samples.Chi-square test was employed to analyze the association of LRRTM1 methylation and clinicopathological factors.Kaplan-Meier survival curves were plotted and Log-Rank test was used to compare overall survival.Univariate and multivariate Cox regression analyses were used to evaluate prognostic factors.Results The expression of LRRTM1 was lost in Capan1,Panc3.11,AsPC1 and PANC-28 cells,and the promoter region of LRRTM1 was completely methylated in these cells.LRRTM1 was normally expressed in Capan2 and CFpac1 cells,and the promoter region of LRRTM1 was unmethylated.The expression of LRRTM1 was restored in Capan1,Panc3.11,AsPC1 and PANC-28 cells,and unchanged in Capan2 and CFpac1 cells after 5-aza-dc treatment.These results indicated that the expression of LRRTM1 was regulated by promoter methylation in pancreatic cancer.It was further found that LRRTM1 was methylated in 16.83%(17/101)of precancerous samples and 52.35%(145/277)of primary pancreatic cancer,and the expression of LRRTM1 was associated with age(P<0.05).For 232 cases of pancreatic cancer patients with available survival data,LRRTM1 methylation was found to be significantly associated with poor overall survival(P<0.05).Conclusion LRRTM1 gene is frequently methylated in pancreatic cancer,and its expression is regulated by promoter methylation.LRRTM1 methylation is a potential diagnostic and prognostic marker for pancreatic cancer.

关 键 词：LRRTM1 胰腺癌 DNA甲基化 甲基化特异性PCR 

分 类 号：R735.9[医药卫生—肿瘤]