非小细胞肺癌患者组织和血清的CFLAR-AS1水平及临床意义

CFLAR-AS1 levels in tissues and sera of patients with non-small cell lung cancer and their clinical significance

目的探讨CFLAR反义RNA 1(CFLAR-AS1)在非小细胞肺癌(NSCLC)患者组织和血清中的水平及临床意义。方法利用GEPIA在线数据库分析TCGA肿瘤组织数据库和GTEx正常组织数据库中NSCLC组织的CFLAR-AS1水平,Kaplan-Meier Plotter在线分析组织CFLAR-AS1水平与NSCLC预后[总生存期(OS)、首次进展后生存期(FP)和复发后生存期(PPS)]的关系。采用实时定量PCR(qPCR)检测102例NSCLC患者和89例健康体检者的血清CFLAR-AS1水平并采用受试者工作特征(ROC)曲线评估血清CFLAR-AS1水平鉴别NSCLC的临床效能,分析血清CFLAR-AS1水平与临床病理特征和预后的关系。结果NSCLC组织(483例腺癌和486例鳞癌)的CFLAR-AS1水平高于正常组织(P<0.05);102例NSCLC患者的血清CFLAR-AS1水平为0.781±0.323,低于健康体检者的1.897±0.642(P<0.001)。ROC曲线分析显示血清CFLAR-AS1水平诊断NSCLC的曲线下面积为0.934(95%CI:0.901~0.967),取1.314为截断值时约登指数最大,灵敏度和特异度分别为93.14%和78.65%。31例早期患者的术前CFLAR-AS1水平为0.986±0.345,低于术后的2.052±0.606(P<0.001)。血清CFLAR-AS1水平与淋巴结转移、分化程度、TNM分期和T分期有关(P<0.05),而与年龄、性别、吸烟史、病理类型和远处转移无关(P>0.05)。Kaplan-Meier Plotter在线分析发现组织CFLAR-AS1水平与OS、FP和PPS均无关(P>0.05)。56例晚期患者的血清CFLAR-AS1水平与PFS有关而与OS无关,其低水平组的中位PFS为9.0个月,低于高水平组的12.0个月(P<0.05)。多因素分析发现高血清CFLAR-AS1水平是PFS的保护因素(OR=0.429,95%CI:0.217~0.789,P=0.016)。结论NSCLC患者的组织和血清CFLAR-AS1水平降低,且血清CFLAR-AS1水平与恶性病理特征和疾病进展有关,血清CFLAR-AS1水平可作为NSCLC诊断及预后评估的潜在指标。

Objective To investigate the level and clinical significance of CFLAR antisense RNA 1(CFLAR-AS1)in tissues and sera of patients with non-small cell lung cancer(NSCLC).Methods GEPIA online database was used to analyze the CFLAR-AS1 levels of NSCLC in TCGA tumor tissue database and GTEX normal tissue database.Kaplan-Meier Plotter online was used to analyze the relationship between CFLAR-AS1 level and prognosis of NSCLC including overall survival(OS),first progression(FP)and post-progression survival(PPS).Real-time quantitative PCR(qPCR)was used to detect the serum levels of CFLAR-AS1 in 102 patients with NSCLC and 89 healthy subjects.The clinical efficacy of identifying NSCLC was evaluated by receiver operating characteristic(ROC)curve,and relationship of serum CFLAR-AS1 level with clinicopathological parameters and prognosis were analyzed.Results The CFLAR-AS1 level in NSCLC tissues including 483 adenocarcinoma and 486 squamous cell carcinoma were higher than that in normal tissues(P<0.05).The serum CFLAR-AS1 level in 102 patients with NSCLC was 0.781±0.323,lower than 1.897±0.642 in the healthy physical examiners(P<0.001).ROC curve analysis showed that the area under the curve of serum CFLAR-AS1 level in the diagnosis of NSCLC was 0.934(95%CI:0.901-0.967).When 1.314 was taken as the cut-off value,the Jordan index was the largest with the sensitivity of 93.14%and specificity of 78.65%.The preoperative level of CFLAR-AS1 in 31 early-stage patients was 0.986±0.345,lower than 2.052±0.606 of the postoperative level(P<0.001).The serum CFLAR-AS1 level was related to lymph node metastasis,degree of differentiation,TNM stage and T stage(P<0.05),but not to age,sex,smoking history,pathological type and distant metastasis(P>0.05).Kaplan-Meier Plotter online analysis found that the CFLAR-AS1 level was not related to OS,FP and PPS(P>0.05).The serum CFLAR-AS1 level in 56 patients with advanced-stage NSCLC was related to PFS but not related to OS.The median PFS in the low-level group was 9.0 months,lower than 12.0 months in the high-level group(P<0.05).Multivariate analysis showed that high serum CFLAR-AS1 level was a protective factor for PFS(OR=0.429,95%CI:0.217-0.789,P=0.016).Conclusion The tissue and serum levels of CFLAR-AS1 in patients with NSCLC are decreased.The serum CFLAR-AS1 level is related to malignant pathological features and disease progression.The serum CFLAR-AS1 level can be used as a potential index for the diagnosis and prognosis of NSCLC.