lncRNA CASC11在膀胱癌患者中的表达及其临床意义

Expression and clinical significance of IncRNA CASC11 in bladder cancer patients

目的探究膀胱癌(BC)患者血清长链非编码RNA (lncRNA)肿瘤易感候选基因11(lncRNA CASC11)的表达水平及其临床意义。方法选取2016年1月至2019年3月在复旦大学附属徐汇医院收治的98例BC患者(BC组)和95例良性泌尿系统疾病患者(良性疾病组)的临床资料, 并选取同期98例健康体检者设为对照组。以BC患者的血清lncRNA CASC11平均表达水平为界, 分为lncRNA CASC11高表达组(50例)和lncRNA CASC11低表达组(48例)。比较各组的血清lncRNA CASC11、细胞角蛋白19片段(CYFRA21-1)、糖类抗原125(CA125)水平;比较不同临床特征的BC患者的血清lncRNA CASC11表达水平;分析血清lncRNA CASC11、CYFRA 21-1、CA125对BC的诊断价值;分析BC患者的血清lncRNA CASC11表达水平与CYFRA 21-1、CA125的相关性;分析血清lncRNA CASC11表达水平与BC患者预后的关系。结果与对照组比较, 良性疾病组、BC组患者的血清lncRNA CASC11、CYFRA 21-1、CA125水平均升高(均P<0.001);与良性疾病组比较, BC组患者的血清lncRNA CASC11、CYFRA 21-1、CA125水平均升高(均P<0.05)。Ⅲ~Ⅳ期的BC患者血清lncRNA CASC11表达水平均高于Ⅰ~Ⅱ期的BC患者(均P<0.001), 发生淋巴结转移的BC患者血清lncRNA CASC11表达水平高于无淋巴结转移的BC患者(P<0.001);血清lncRNA CASC11、CYFRA 21-1诊断BC的曲线下面积(AUC)分别为0.875、0.848, 高于CA125(AUC=0.675), lncRNA CASC11、CYFRA 21-1联合诊断BC的AUC为0.941, 高于二者单独诊断, 且联合诊断BC的灵敏度为91.8%, 特异度为86.3%。BC患者的血清lncRNA CASC11表达水平与CYFRA 21-1、CA125均呈正相关(均P<0.05);经Kaplan-Meier生存分析结果显示, lncRNA CASC11低表达组的平均生存期为34.63个月(95%CI:33.37~35.88), lncRNA CASC11高表达组的平均生存期为30.12个月(95%CI:27.57~32.67), 差异有统计学意义(P<0.05);log-rank检验结果显示, lncRNA CASC11低表达组的累积生存率高于lncRNA CASC11高表达组, 差异有统计学意义(χ^(2)=9.136, P=0.003)。结论 lncRNA CASC11在BC患者的血清中表达上调, 检测血清lncRNA CASC11表达水平可有助于临床诊断、评估BC患者的预后。

Objective To investigate the expression level and clinical significance of serum long non-coding RNA(IncRNA)cancer susceptibility candidate gene 11(IncRNA CASC11)in patients with bladder cancer(BC).Methods A total of 98 patients with BC and 95 patients with benign urinary system diseases who were admitted to Fudan University Affiliated Xuhui Hospital from January 2016 to March 2019 were taken as the BC group and the benign disease group,respectively,meantime,98 healthy subjects were taken as the control group.According to the average expression level of serum IncRNA CASCI1 in BC patients,the patients were divided into lncRNA CASC11 high expression group(50 cases)and IncRNA CASC11 low expression group(48 cases).Serum levels of lncRNA CASC11,cytokeratin 19 fragment(CYFRA21-1)and carbohydrate antigen 125(CA125)were compared among the three groups.The expression levels of serum lncRNA CASC11 in BC patients with different clinical characteristics were compared.The diagnostic value of serum IncRNA CASC11,CYFRA 21-1 and CA125 in BC was analyzed.The correlation between the expression level of serum lncRNA CASC11 and CYFRA 21-1 and CA125 in BC patients was analyzed.The relationship between serum lncRNA CASC1l expression level and the prognosis of BC patients was analyzed.Results Compared with control group,serum lncRNA CASC11,CYFRA 21-1 and CA125 levels in benign disease group and BC group were increased(all P<0.001).Compared with benign disease group,serum lncRNA CASC11,CYFRA 21-1 and CA125 levels in BC group were increased(all P<0.05).The serum lncRNA CASCI1 expression level of BC patients in stage II to IV was higher than that of BC patients in stage ⅢtoⅣ(all P<0.001),and the serum IncRNA CASC11 expression level of BC patients with lymph node metastasis was higher than that of BC patients without lymph node metastasis(P<0.001).The area under the curve(AUC)of serum lncRNA CASC11 and CYFRA 21-1 for the diagnosis of BC were 0.875 and 0.848,respectively,higher than that of CA125(AUC=0.675).In addition,the AUC of the combined diagnosis of BC by lncRNA CASC11 and CYFRA 21-1 was O.941,which was higher than that of the two alone diagnosis,and the sensitivity and specificity of the combined diagnosis of BC were 91.8%and 86.3%.The expression level of serum IncRNA CASC11 in BC patients was positively correlated with CYFRA 21-1 and CA125(allP<0.05).Kaplan-Meier survival analysis showed that the average survival time of BC patients in the low IncRNA CASCII expression group was 34.63 months(95%CI:33.37-35.88),and the average survival time of BC patients in the high lncRNA CASC11 expression group was 30.12 months(95%CI:27.57-32.67),the difference was statistically significant(P<0.05);log-rank test results showed that the cumulative survival rate of BC patients in the low lncRNA CASC11 expression group was higher than that in the high IncRNA CASC11 expression group,and the dfference was statistically significant(Х^(2)=9.136,P=0.003).Conclusions The expression of IncRNA CASC11 is up-regulated in the serum of BC patients,and the detection of serum IncRNA CASC11 expression level can be helpful for clinical diagnosis of BC and evaluation of the prognosis of BC patients.