环状RNA ciRS-7、circ_0058514和circ-Foxo3在食管鳞癌患者癌组织与血清中的表达及意义

Expression and Significance of Cyclic RNA CiRS-7,Circ_0058514 and Circ-Foxo3 in Serum and Cancer Tissues of Patients with Esophageal Squamous Cell Carcinoma

[目的]探讨环状RNA ciRS-7、circ0058514和circ-Foxo3在食管鳞癌患者癌组织与血清中的表达及意义。[方法]选择2015年1月—2017年6月在河南省肿瘤医院接受食管鳞癌手术治疗的97例食管鳞癌患者,以同期于本院健康体检的97名健康者为对照组。分析所有患者的一般资料,包括肿瘤位置、直径、分化程度、TNM分期、有无淋巴结转移等;采用荧光定量PCR测定癌组织、癌旁组织和术前术后血清中环状RNAciRS-7、circ0058514和circ-Foxo3表达水平。统计分析不同组间ciRS-7、circ0058514和circ-Foxo3表达差异与食管鳞癌患者临床特征的关系。术后随访患者并计算其1年、2年和3年生存率,单因素生存分析ciRS-7、circ0058514和circ-Foxo3表达与生存率之间的关系,Cox回归分析影响患者生存时间的危险因素,Pearson相关性分析癌组织和血清中ciRS-7、circ0058514和circ-Foxo3水平间的关系。[结果]食管鳞癌癌组织中ciRS-7和circ0058514表达水平明显高于癌旁组织,circ-Foxo3表达水平明显低于癌旁组织(P<0.05),且其水平变化与患者TNM分期和淋巴结转移有关(P<0.05);癌组织中ciRS-7高表达患者1年无病生存率,2年、3年总生存率和无病生存率均低于ciRS-7低表达患者(P<0.05),circ0058514高表达患者1年无病生存率低于circ0058514低表达患者(P<0.05),circ-Foxo3高表达患者2年和3年总生存率和无病生存率均高于circ-Foxo3低表达患者(P<0.05);TNM分期为Ⅲ期(OR=0.516,P=0.040)、合并淋巴结转移(OR=0.485,P=0.019)、ciRS-7高表达(OR=0.523,P=0.037)、circ-Foxo3低表达(OR=1.929,P=0.030)为影响食管鳞癌患者3年无病生存率的独立危险因素;食管鳞癌患者血清ciRS-7和circ0058514水平明显高于对照组,circ-Foxo3水平明显低于对照组(t=14.680,14.659,15.202,P<0.05),且术后血清ciRS-7和circ0058514水平明显低于术前,circ-Foxo3水平明显高于术前(t=7.998,5.103,8.372,P<0.05);术前癌组织和血清中ciRS-7、circ0058514和circ-Foxo3水平具有一致性(r=0.776,0.722,0.789,P<0.05),且ciRS-7和circ-Foxo3呈显著负相关关系(r=-0.422,-0.338,P<0.05)。[结论]食管鳞癌癌组织和血清中ciRS-7和circ0058514表达水平明显升高,circ-Foxo3表达水平明显降低,且其水平变化与患者的生存有关。

[Purpose]To investigate the expression and significance of cyclic RNA ciRS-7,circ0058514 and circFoxo3 in serum and cancer tissues of patients with esophageal squamous cell carcinoma.[Methods]Ninety-seven patients with esophageal squamous cell carcinoma who underwent surgical treatment in Henan Cancer Hospital from January 2015 to June 2017 and 97 healthy subjects(control group)were enrolled in the study.The expression of ciRS-7,circ0058514,circ-Foxo3 in cancer tissues,para-cancerous tissues and serum before and after surgery were detected by fluorescent quantitative RT-PCR.The patients were followed up after treatment and 1-year,2-year and 3-year survival rates were calculated.The relationship of ciRS-7,circ0058514,circ-Foxo3 expression with the clinicopathological features and the survival of patients were analyzed.The risk factors affecting the survival time of patients were analyzed by Cox analysis.The relationship between ciRS-7,circ0058514 and circ-Foxo3 levels in cancer tissues and serum were analyzed by Pearson correlation analysis.[Results]The expression levels of ciRS-7 and circ0058514 in cancer tissues were significantly higher than those in para-cancerous tissues,while the levels of circ-Foxo3 were significantly lower than that in para-cancerous tissues(P<0.05).Moreover,their expression levels were related to TNM staging and lymph node metastasis(P<0.05).The 1-year disease-free survival(DFS)rate,2-year and 3-year overall survival(OS)rates and DFS rates in patients with high-expression ciRS-7 were lower than those with low-expression ciRS-7(P<0.05).The 1-year DFS rate in patients with high-expression circ0058514 was lower than those with low-expression circ0058514(P<0.05).The 2-year and 3-year OS rates and DFS rates in patients with high-expression circ-Foxo3 were higher than those with low-expression circ-Foxo3(P<0.05).TNM stageⅢ(OR=0.516,P=0.040),lymph node metastasis(OR=0.485,P=0.019),ciRS-7 high expression(OR=0.523,P=0.037)and circ-Foxo3 low expression(OR=1.929,P=0.030)were independent risk factors for 3-year DFS of patients.The levels of serum ciRS-7 and circ0058514 in patients were significantly higher than those in control group,while the level of circ-Foxo3 was significantly lower than that in control group(t=14.680,14.659,15.202,P<0.05).The levels of serum ciRS-7 and circ0058514 after surgery were significantly lower than those before surgery,while the level of circ-Foxo3 after surgery was significantly higher than that before surgery(t=7.998,5.103,8.372,P<0.05).The levels of ciRS-7,circ005851 and circ-Foxo3 in cancer tissues and serum before surgery were correlated with each other(r=0.776,0.722,0.789,P<0.05).There was significant negative correlation between ciRS-7 and circ-Foxo3(r=-0.422,-0.338,P<0.05).[Conclusion]The expression levels of ciRS-7 and circ0058514 are significantly increased in serum and cancer tissues,while the expression level of circ-Foxo3 is significantly decreased in patients with esophageal squamous cell carcinoma,which are correlated with the survival of patients.