结直肠癌患者血清外泌体的JHDM1D-AS1水平及临床意义  

Level and clinical significance of serum exosomal JHDM1D-AS1 in patients with colorectal cancer

作　　者：孔桂香[1] 高丽萍 朱华 李俊杰[2] 张学花 KONG Guixiang;GAO Liping;ZHU Hua;LI Junjie;ZHANG Xuehua(Department of Gastroenterology,the Second Hospital of Lanzhou University,Lanzhou 730030,China)

机构地区：[1]兰州大学第二医院消化科,兰州730030 [2]中国人民解放军63600部队医院消化科,732750

出　　处：《临床肿瘤学杂志》2021年第8期729-735,共7页Chinese Clinical Oncology

摘　　要：目的探讨结直肠癌(CRC)患者血清外泌体的JHDM1D反义RNA 1(JHDM1D-AS1)水平及临床意义。方法利用GEPIA在线数据库分析TCGA肿瘤组织数据库中CRC组织的JHDM1D-AS1水平,Ualcan网站在线分析JHDM1D-AS1与CRC预后的关系。采用实时定量PCR(qPCR)检测119例CRC患者血清外泌体的JHDM1D-AS1水平并以93例健康体检者和34例良性肠道疾病患者为参考采用受试者工作特征(ROC)曲线评估血清外泌体的JHDM1D-AS1水平鉴别CRC的效能,根据临床病理特征和随访资料结合Cox比例风险回归模型来进一步分析血清外泌体的JHDM1D-AS1水平在CRC中的临床意义。结果CRC组织(275例结肠癌和92例直肠癌)的JHDM1D-AS1水平均高于正常组织(P<0.05),且组织JHDM1D-AS1水平仅与结肠癌的总生存期(OS)有关,其中高JHDM1D-AS1水平者的OS较差(P<0.05)。119例CRC患者血清外泌体的JHDM1D-AS1水平为2.652±0.882,高于健康体检者的1.267±0.442和良性肠道疾病患者的1.175±0.362(P<0.05),ROC曲线分析显示CRC对比健康对照和良性肠道疾病的血清外泌体JHDM1D-AS1的曲线下面积为0.927(95%CI:0.894~0.959,最优截断点1.970的诊断灵敏度和特异度分别为77.31%和94.62%)和0.949(95%CI:0.918~0.981,最优截断点1.779的诊断灵敏度和特异度分别为83.19%和94.12%)。血清外泌体JHDM1D-AS1水平与CRC的肿瘤大小、淋巴结转移、分化程度、TNM分期和浸润深度有关(P<0.05),而与年龄、性别、肿瘤位置和远处转移无关(P>0.05)。单因素分析显示血清外泌体JHDM1D-AS1水平与OS有关,其中低水平组的中位OS为57.0个月及1、3、5年总生存率分别为94.3%、82.7%和45.6%,优于高水平组的42.0个月及92.6%、61.2和11.7%(P<0.05),多因素分析发现高外泌体JHDM1D-AS1水平是OS的危险因素(OR=2.615,95%CI:1.697~4.274,P=0.004)。结论CRC患者血清外泌体JHDM1D-AS1水平升高且与恶性病理特征和预后有关,该指标有望成为CRC诊断及预后评估的潜在指标。Objective To investigate the level and clinical significance of serum exosomal JHDM1D antisense RNA 1(JHDM1D-AS1)in patients with colorectal cancer(CRC).Methods GEPIA online database was applied to analyze the JHDM1D-AS1 level of CRC tissue in TCGA tumor tissue database,and Ualcan website was used to analyze the relationship between JHDM1D-AS1 and prognosis of CRC patients.Real-time quantitative PCR(qPCR)was used to detect the serum exosomal level of JHDM1D-AS1 in 119 patients with CRC,and 93 healthy subjects and 34 patients with benign intestinal diseases were used as reference.The receiver operating characteristic(ROC)curve was used to evaluate the serum exosomal level of JHDM1D-AS1 to identify CRC.Clinical significance of serum exosomal level of JHDM1D-AS1 in CRC was further analyzed according to clinicopathological features and follow-up data combined with Cox proportional hazards regression model.Results JHDM1D-AS1 levels in CRC tissues including 275 cases of colon cancer and 92 cases of rectal cancer were higher than that in normal tissues(P<0.05).JHDM1D-AS1 level was only related to the overall survival(OS)of colon cancer,among which the OS of those with high JHDM1D-AS1 level was poor(P<0.05).The serum exosomal level of JHDM1D-AS1 in 119 CRC patients was 2.652±0.882,higher than 1.267±0.442 in healthy subjects and 1.175±0.362 in patients with benign intestinal diseases(P<0.05).ROC curve analysis showed that the area under the curve of serum exosomal JHDM1D-AS1 level in CRC compared with healthy controls and benign intestinal diseases was 0.927(95%CI ranging from 0.894 to 0.959 and optimal cutoff of 1.970 with the diagnostic sensitivity of 77.31%and specificity of 94.62%)and 0.949(95%CI ranging from 0.918 to 0.981 and optimal cutoff of 1.779 with the diagnostic sensitivity of 83.19%and specificity of 94.12%).The serum exosomal level of JHDM1D-AS1 was related to tumor size,lymph node metastasis,degree of differentiation,TNM stage and depth of invasion of CRC(P<0.05),but not to age,gender,tumor location and

关 键 词：结直肠癌 JHDM1D反义RNA 1 血清外泌体 临床意义 预后 

分 类 号：R735.2[医药卫生—肿瘤]