结直肠癌患者组织和血清外泌体的LASTR水平及临床意义

Clinical significance of LASTR levels in tissues and serum exosomes of patients with colorectal cancer

目的探讨结直肠癌患者组织和血清外泌体的LASTR水平及临床意义。方法基于UALCAN在线分析结直肠癌组织的LASTR水平及其与预后的关系。差速超速离心法制备146例结直肠癌患者和127例健康体检者的血清外泌体后采用实时定量PCR(qPCR)检测LASTR水平,分析血清外泌体LASTR水平与结直肠癌临床病理特征的关系,受试者工作特征(ROC)曲线分析外泌体LASTR水平诊断结直肠癌的效能,结合随访数据和多因素分析进行生存分析。结果478例结肠癌组织的LASTR水平[中位数(25%~75%四分位数范围)]为0.173(0.061~0.351),高于41例正常组织的0.031(0~0.065),166例直肠癌组织的LASTR水平为0.137(0.059~0.267),高于10例正常组织的0.010(0~0.042),差异有统计学意义(P<0.05);结肠癌组织的LASTR水平与总生存期(OS)有关,其中高水平者的OS较短(P<0.05)。结直肠癌患者的外泌体LASTR水平为4.538(3.280~5.662),高于健康体检者的1.701(1.298~2.411),差异有统计学意义(P<0.05)。ROC曲线分析显示外泌体LASTR水平诊断结直肠癌的曲线下面积为0.929(95%CI:0.900~0.958),当最佳截断值为3.020时约登指数最大,灵敏度和特异度分别为80.14%和92.91%。外泌体LASTR水平与淋巴结转移、分化程度、远处转移、浸润深度、TNM分期和OS有关(P<0.05),而与年龄、性别、肿瘤部位和肿瘤大小无关(P>0.05)。外泌体LASTR低水平组的中位OS未达,优于高水平组的47.0个月(HR=5.494,95%CI:3.040~9.928,P<0.001),多因素分析发现外泌体LASTR水平是OS的危险因素(HR=4.165,95%CI:2.974~6.138,P=0.017)。结论结直肠癌组织和外泌体LASTR水平升高且参与了结直肠癌的进展,外泌体LASTR水平对于结直肠癌诊断和预后预测有一定价值。

Objective To investigate the clinical significance of lncRNA associated with SART3 regulation of splicing(LASTR)levels in tissues and serum exosomes of patients with colorectal cancer.Methods LASTR level in colorectal cancer tissues and its relationship with prognosis were on-line analyzed by UALCAN.After extracting serum exosomes from 146 patients with colorectal cancer and 127 healthy people via ultra-centrifugation method,LASTR levels were detected by real-time quantitative PCR(qPCR).Relationship between serum exosomal LASTR level and clinicopathological characteristics of colorectal cancer was analyzed.Efficacy of exosomal LASTR level in the diagnosis of colorectal cancer was analyzed by receiver operating characteristic(ROC)curve.Survival analysis was performed combined with follow-up data and multivariate analysis.Results The LASTR level[median(25%-75%quartile range)]in 478 cases of colon cancer tissue was 0.173(0.061-0.351),higher than 0.031(0-0.065)in 41 cases of normal tissues,and 0.137(0.059-0.267)in 166 cases of rectal cancer tissues,higher than 0.010(0-0.042)in 10 cases of normal tissues(P<0.05).LASTR level in colon cancer was related to the overall survival(OS),and the OS of those with high level was shorter(P<0.05).Exosomal LASTR level in patients with colorectal cancer was 4.538(3.280-5.662),higher than 1.701(1.298-2.411)in healthy subjects(P<0.05).ROC curve analysis showed that the area under the curve for the diagnosis of colorectal cancer was 0.929(95%CI:0.900-0.958),and when the optimal cut-off value was 3.020,the Yoden index was the largest with the sensitivity of 80.14%and specificity of 92.91%.Exosomal LASTR level was related to lymph node metastasis,differentiation degree,distant metastasis,invasion depth,TNM stage and OS(P<0.05),but not to age,sex,tumor location and tumor size(P>0.05).The median OS in the low-level group of exosomal LASTR was unreached,longer than 47.0 months in the high-level group(HR=5.494,95%CI:3.040-9.928,P<0.001).Multivariate analysis found that the exosomal LASTR level was a risk factor for OS(HR=4.165,95%CI:2.974-6.138,P=0.017).Conclusion Elevated exosomal LASTR levels in tissues and serum exosomes of patients with colorectal cancer were involved in the progression of colorectal cancer.The exosomal LASTR level has a certain value for the diagnosis and prognosis of colorectal cancer.