食管鳞癌组织的CADM2-AS1和CADM2-AS2水平及临床意义

Levels and clinical significances of CADM2-AS1 and CADM2-AS2 in esophageal squamous cell carcinoma tissues

目的探讨食管鳞癌(ESCC)组织的细胞粘附分子2(CADM2)反义RNA 1(CADM2-AS1)和CADM2反义RNA 2(CADM2-AS2)水平及临床意义。方法采用实时定量PCR(qPCR)检测本院2015年1月至2019年12月手术切除的116对ESCC组织和对应癌旁组织的CADM2、CADM2-AS1和CADM2-AS2水平,比较ESCC组织和癌旁组织中上述指标的水平差异,分析ESCC组织中CADM2、CADM2-AS1和CADM2-AS2水平的相关性及与临床病理特征的关系,根据随访数据并结合Kaplan-Meier法进行生存分析,Log-rank检验和Cox风险比例模型探讨CADM2、CADM2-AS1和CADM2-AS2在ESCC预后预测中的意义。结果ESCC组织的CADM2、CADM2-AS1和CADM2-AS2水平为0.608±0.021、0.785±0.028和0.677±0.025,低于对应癌旁组织的1.401±0.052、2.519±0.096和2.741±0.103,差异均有统计学意义(P<0.05);相关分析显示,CADM2与CADM2-AS1和CADM2-AS2水平呈正相关(r=0.214、0.418,P<0.001),CADM2-AS1和CADM2-AS2水平亦呈正相关(r=0.613,P<0.001)。分层分析发现CADM2水平与肿瘤直径、分化程度、浸润深度和TNM分期有关,CADM2-AS1水平与肿瘤直径、浸润深度、淋巴结转移和TNM分期有关,而CADM2-AS2水平与分化程度、淋巴结转移和TNM分期有关(P<0.05)。生存分析发现肿瘤直径、浸润深度、淋巴结转移、TNM分期、CADM2和CADM2-AS2水平与ESCC的总生存期(OS)有关(P<0.05),其中CADM2和CADM2-AS2高水平的中位OS均未达,优于低水平的35.0和46.0个月(P<0.05),进一步多因素分析发现ESCC组织的CADM2和CADM2-AS2水平降低是OS不良的风险因素(HR=4.513,95%CI:2.127~8.514,P=0.021;HR=1.854,95%CI:1.069~3.547,P=0.036)。结论ESCC组织中CADM2、CADM2-AS1和CADM2-AS2水平下调与ESCC的恶性临床指标有关,在一定程度上参与了ESCC的发生发展,CADM2/CADM2-AS2在ESCC预后预测上有一定价值。

Objective To investigate the levels and clinical significances of cell adhesion molecule 2(CADM2)antisense RNA 1(CADM2-AS1)and CADM2 antisense RNA 2(CADM2-AS2)in esophageal squamous cell carcinoma(ESCC)tissues.Methods Levels of CADM2,CADM2-AS1 and CADM2-AS2 in 116 pairs of ESCC tissues and corresponding adjacent tissues surgically removed in our hospital from January 2015 to December 2019 were detected by real-time quantitative PCR(qPCR).Levels of the above indices in ESCC and adjacent tissues were compared,and correlations between levels of CADM2,CADM2-AS1 and CADM2-AS2 in ESCC and clinicopathological features were analyzed.The significance of CADM2,CADM2-AS1 and CADM2-AS2 in predicting the prognosis of ESCC was discussed according to the follow-up data via Kaplan-Meier method,Log rank test and Cox risk ratio model.Results Levels of CADM2,CADM2-AS1 and CADM2-AS2 in ESCC tissues were 0.608±0.021,0.785±0.028 and 0.677±0.025,which were significantly lower than 1.401±0.052,2.519±0.096 and 2.741±0.103 in adjacent tissues(P<0.05).Correlation analysis showed that CADM2 level was positively correlated with levels of CADM2-AS1 and CADM2-AS2(r=0.214 and 0.418,P<0.001),and levels of CADM2-AS1 and CADM2-AS2 were also positively correlated(r=0.613,P<0.001).Stratified analysis showed that CADM2 level was related to tumor diameter,degree of differentiation,depth of invasion and TNM stage,CADM2-AS1 level was related to tumor diameter,depth of invasion,lymph node metastasis and TNM stage,while CADM2-AS2 level was related to degree of differentiation,lymph node metastasis and TNM stage(P<0.05).Survival analysis revealed tumor diameter,depth of invasion,lymph node metastasis,TNM stage and levels of CADM2 and CADM2-AS2 were related to the overall survival(OS)of ESCC(P<0.05).The median OS of patients with high levels of CADM2 and CADM2-AS2 were not reached,better than 35.0 and 46.0 months of patients with low levels(P<0.05).Further multivariate analysis found that the reduction of CADM2 and CADM2-AS2 levels in ESCC was a risk factor for poor OS(HR=4.513,95%CI:2.127-8.514,P=0.021;HR=1.854,95%CI:1.069-3.547,P=0.036).Conclusion The down-regulation of CADM2,CADM2-AS1 and CADM2-AS2 levels in ESCC is related to the malignant clinical indicators of ESCC,and participates in the occurrence and development of ESCC to a certain extent.CADM2/CADM2-AS2 have a certain value in predicting the prognosis of ESCC.