胃癌组织的LCMT1-AS2水平及临床意义

Level and clinical significance of LCMT1-AS2 in gastric cancer tissues

目的探讨胃癌组织中长链非编码RNA LCMT1反义RNA 2(LCMT1-AS2)的水平及临床意义。方法基于UALCAN在线分析癌症基因组图谱(TCGA)数据库中375例胃癌组织和32例正常组织的LCMT1-AS2水平,通过NCBI提供的GEO2R平台检索GEO数据库GSE54129中111例胃癌组织和21例正常组织的LCMT1-AS2水平,采用实时定量PCR(qPCR)检测本院2015年1月至2019年12月手术切除的117例胃癌组织和103例癌旁正常组织的LCMT1-AS2水平,分层分析LCMT1-AS2水平与胃癌临床病理特征(性别、年龄、Lauren分型、肿瘤直径、TNM分期、分化程度、淋巴结转移和浸润深度)的关系,Kaplan-Meier法进行生存分析并采用Engauge Digitizer软件在生存曲线上提取1、3、5年生存率。结果TCGA数据库和GSE54129数据集中胃癌组织的LCMT1-AS2水平均高于正常组织(P<0.05);qPCR结果显示胃癌组织的LCMT1-AS2水平为3.413±1.463,高于癌旁组织的1.735±0.735(P<0.05);LCMT1-AS2水平与胃癌的性别、年龄和分化程度无关(P>0.05),而与Lauren分型、肿瘤直径、TNM分期、淋巴结转移和浸润深度有关(P<0.05)。Kaplan-Meier Plotter数据库分析显示LCMT1-AS2高水平者的中位总生存期(OS)为36.4个月,短于低水平者的70.4个月(HR=1.30,95%CI:1.04~1.62,P=0.021)。LCMT1-AS2低水平者的1、3、5年总生存率分别为98.4%、76.0%和48.1%,高于LCMT1-AS2高水平者的92.9%、40.9%和9.8%,中位OS为50.0个月,长于LCMT1-AS2高水平者的34.0个月,差异有统计学意义(P<0.05)。多因素分析显示,LCMT1-AS2高水平为胃癌患者预后不良的危险因素(HR=3.451,95%CI:1.259~6.257,P<0.05)。结论LCMT1-AS2在胃癌组织中高表达,且该指标水平异常升高与恶性程度和不良预后有关,一定程度上参与胃癌的发生发展,可作为胃癌诊治的候选靶点。

Objective To investigate the level and clinical significance of long non-coding RNA LCMT1 antisense RNA 2(LCMT1-AS2)in gastric cancer tissues.Methods LCMT1-AS2 levels in 375 cases of gastric cancer tissues and 32 cases of normal tissues in The Cancer Genome Atlas(TCGA)database were analyzed based on the UALCAN online.LCMT1-AS2 levels in 111 cases of gastric cancer tissues and 21 cases of normal tissues were retrieved from GEO database GSE54129 by GEO2R platform provided by NCBI.LCMT1-AS2 levels in 117 cases of gastric cancer tissues and 103 cases of adjacent normal tissues from January 2015 to December 2019 were detected by real-time quantitative PCR(qPCR).The relationship between LCMT1-AS2 levels and clinicopathological characteristics(gender,age,Lauren classification,tumor diameter,TNM stage,degree of differentiation,lymph node metastasis and depth of invasion)of gastric cancer was analyzed by stratified analysis.Kaplan-Meier method was used for survival analysis.Engauge digitizer software was used to extract the 1,3 and 5-year survival rate on the survival curve.Results LCMT1-AS2 levels in gastric cancer tissues in TCGA database and GSE54129 dataset were higher than those in normal tissues(P<0.05).QPCR results showed that the LCMT1-AS2 level in gastric cancer tissues was 3.413±1.463,higher than 1.735±0.735 in adjacent tissues(P<0.05).LCMT1-AS2 was not related to gender,age and differentiation degree of gastric cancer(P>0.05),but related to Lauren type,tumor diameter,TNM stage,lymph node metastasis and depth of invasion(P<0.05).Kaplan-Meier Plotter database analysis showed that the median overall survival(OS)of patients with high-level of LCMT1-AS2 was 36.4 months,shorter than 70.4 months of patients with low-level of LCMT1-AS2(HR=1.30,95%CI:1.04-1.62,P=0.021).The 1,3,and 5-year overall survival rates of patients with low-level LCMT1-AS2 were 98.4%,76.0%and 48.1%,higher than 92.9%,40.9%and 9.8%of patients with high-level LCMT1-AS2(P<0.05).The median OS of patients with low-level LCMT1-AS2 was 50.0 months,longer than 34.0 months of patients with high-level LCMT1-AS2(P<0.05).Multivariate analysis showed that high level of LCMT1-AS2 was a risk factor for poor prognosis of gastric cancer patients(HR=3.451,95%CI:1.259-6.257,P<0.05).Conclusion LCMT1-AS2 is highly expressed in gastric cancer,and the abnormal increase of LCMT1-AS2 level is related to the degree of malignancy and poor prognosis.To some extent,LCMT1-AS2 is involved in the occurrence and development of gastric cancer,and can be used as a candidate target for the diagnosis and treatment of gastric cancer.