环状RNA hsa_circ_002059在胃癌患者组织与循环血液中的表达及意义

Expression and significance of circular RNA hsa_circ_002059 in gastric cancer tissues and circulating blood

目的建立胃癌患者癌组织、血浆和血浆外泌体中hsa_circ_002059表达的检测方法,探讨其在胃癌组织与循环血液中表达的临床应用价值。方法应用circ2Traits和starBase v2.0数据库预测胃癌相关环状RNA hsa_circ_002059的表达;实时荧光定量RT-PCR检测配对的胃癌组织与癌旁组织(87例)、胃癌患者和体检健康者血浆(52例)及外泌体(62例)样本中hsa_circ_002059表达水平的差异,并分析与临床病理参数的相关性;ROC曲线和生存曲线分析评价其在胃癌诊断与预后评估中的临床价值。结果hsa_circ_002059具有多个胃癌相关miRNA结合位点,在胃癌组织中的表达水平显著低于癌旁组织(U=1759.0,P<0.001),且与肿瘤大小有关(χ^(2)=6.183,P=0.013)。组织hsa_circ_002059筛查胃癌的ROC曲线下面积(AUCROC)为0.768,敏感性和特异性分别为0.67和0.92。在胃癌患者血浆中hsa_circ_002059的表达水平明显高于体检健康者(U=1011.5,P=0.027),且与淋巴结转移有关(χ^(2)=12.231,P=0.005)。血浆hsa_circ_002059筛查胃癌的AUCROC为0.626,敏感性和特异性分别为0.65和0.64。此外,hsa_circ_002059高表达患者的平均生存时间显著低于低表达者(χ^(2)=4.594,P=0.032),在胃癌患者血浆外泌体中hsa_circ_002059的表达水平与体检健康者之间的差异无统计学意义(U=1746.0,P=0.379)。结论hsa_circ_002059表达与胃癌进展有关,其在组织和血浆中表达水平的检测有望用于胃癌辅助诊断与预后评估。

Objective To establish a detection method for hsa_circ_002059 in gastric cancer tissues,plasma and plasma exosomes from gastric cancer patients,and investigate its expression level and clinical significance in gastric cancer tissues and circulating blood.Methods Database circ2Traits and starBase v2.0 were used to predict the expression of hsa_circ_002059 as gastric cancer related circular RNA.The differences of expression levels of hsa_circ_002059 in paired gastric cancer tissues and paracancerous tissues(n=87),paired samples of plasma(n=52)and plasma exosome(n=62)from gastric cancer patients and healthy controls were detected by using real-time fluorescence quantitative RT-PCR and analyzed for correlation analysis of clinic pathological features.ROC analysis and overall survival analysis were applied to assess the diagnostic and prognostic values of hsa_circ_002059.Results Hsa_circ_002059 contained multiple miRNA binding sites related to gastric cancer,which significantly downregulated in gastric cancer tissues and was lower than that of the paracancer tissue(U=1759.0,P<0.001),and associated with tumor size(χ^(2)=6.183,P=0.013).The area under ROC curve(AUCROC)of hsa_circ_002059 was 0.768 with a sensitivity of 0.67,a specificity of 0.92 in the tissues for screening gastric cancer.The levels of hsa_circ_002059 markedly upregulated in plasma of gastric cancer patients compared to those of healthy controls(U=1011.5,P=0.027)and associated with lymphatic metastasis(χ^(2)=12.231,P=0.005),showing 0.626 of AUCROC with sensitivity of 0.65 and specificity of 0.64.The mean survival time of gastric cancer patients with high expression of hsa_circ_002059 was significantly shorter than that of low expression(χ^(2)=4.594,P=0.032).No significant difference of the expression levels of hsa_circ_002059 was found in plasma exosomes from gastric cancer patients and healthy controls(U=1746.0,P=0.379).Conclusion The expression of hsa_circ_002059 was related to progression of gastric cancer.The detection of expression levels of hsa_circ_002059 derived from tissue and plasma should be prospective auxiliary diagnosis and estimation of prognosis for gastric cancer.