结肠癌组织中lncRNA TPT1-AS1、miR-30c-5p的表达及与病理特征、预后的关系

Relationship of expression of lncRNA TPT1-AS1 and miR-30c-5p with pathological characteristics and prognosis in colon cancer

目的探讨结肠癌组织中长链非编码RNA(lncRNA)肿瘤蛋白翻译调节因子1(TPT1)-反义RNA1(AS1)、微小RNA(miR)-30c-5p的表达及与病理特征、预后的关系。方法选取2015年1月至2017年12月深圳大学附属第一医院收治的117例接受根治性或姑息性手术切除结肠癌患者,均行手术切除结肠癌组织及癌旁组织。采用qRT-PCR检测lncRNA TPT1-AS1、miR-30c-5p表达水平,分析lncRNA TPT1-AS1、miR-30c-5p表达水平与结肠癌病理特征的关系,采用Pearson相关性检验分析结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平的相关性,Kaplan-Meier曲线绘制不同lncRNA TPT1-AS1、miR-30c-5p表达水平结肠癌患者3年累积生存率,Cox回归分析结肠癌患者预后影响因素。结果结肠癌组织中lncRNA TPT1-AS1表达水平明显高于癌旁组织(3.405±0.555 vs 1.766±0.096),miR-30c-5p表达水平(0.306±0.146 vs 0.872±0.267)明显低于癌旁组织(P<0.05)。结肠癌lncRNA TPT1-AS1表达水平TNM分期Ⅲ~Ⅳ期明显高于Ⅰ~Ⅱ期(3.651±0.579 vs 3.257±0.486),浸润深度T_(3)~T_(4)明显高于T_(1)~T_(2)(3.523±0.601 vs 3.301±0.491),有淋巴结转移明显高于无淋巴结转移(3.614±0.585 vs 3.220±0.456),差异均有统计学意义(P<0.05);miR-30c-5p表达水平TNM分期Ⅲ~Ⅳ期明显低于Ⅰ~Ⅱ期(0.251±0.126 vs 0.346±0.145),浸润深度T_(3)~T_(4)明显低于T_(1)~T_(2)(0.270±0.119 vs 0.338±0.162),有淋巴结转移明显低于无淋巴结转移(0.255±0.125 vs 0.351±0.151),差异均有统计学意义(P<0.05)。Pearson相关性分析显示,结肠癌组织中lncRNA TPT1-AS1与miR-30c-5p表达水平呈负相关(r=-0.572,P<0.05)。Kaplan-Meier生存曲线显示,lncRNA TPT1-AS1高表达水平组3年累积生存率明显低于低表达水平组(59.32%vs 87.93%),miR-30c-5p高表达水平组3年累积生存率明显高于低表达水平组(85.00%vs 61.40%)(P<0.05)。多因素Cox回归分析显示,TNM分期Ⅲ~Ⅳ期(HR=2.387,95%CI:1.004~5.671)、淋巴结转移(HR=2.667,95%CI:1.021~6.969)、lncRNA TPT1-AS1≥3.405(HR=2.023,95%CI:1.076~3.803)为结肠癌患者预后独立风险因素,miR-30c-5p≥0.306(HR=0.175,95%CI:0.012~0.423)为独立保护因素(P<0.05)。结论结肠癌组织中lncRNA TPT1-AS1表达显著上调,miR-30c-5p表达显著下调,两者与TNM分期、浸润深度、淋巴结转移相关,为患者预后独立影响因素,可能成为结肠癌预后评估的标志物。

Objective To detect the expression of the long non-coding RNA(lncRNA)tumor protein translation regulator 1-antisense RNA1(TPT1-AS1)and microRNA(miR)-30c-5p in colon cancer,and to analyze its relationship with pathological characteristics and prognosis.Methods A total of 117 patients with colon cancer who underwent radical or palliative surgery were selected from January 2015 to December 2017 at the First Affiliated Hospital of Shenzhen University.The colon cancer and adjacent tissues were surgically removed,and the expression levels of lncRNA TPT1-AS1 and miR-30c-5p in these tissues were detected by qRT-PCR.The relationship between the expression levels of lncRNA TPT1-AS1 and miR-30C-5p and the pathological features of colon cancer was analyzed,and the correlation between the expression levels of lncRNA TPT1-AS1 and miR-30C-5p in colon cancer tissues was analyzed by Pearson correlation test.Kaplan-Meier curve was used to calculate the 3-year cumulative survival rate of colon cancer patients with different lncRNATPT1-AS1 and miR-30C-5P expression levels,and Cox regression analysis was performed to analyze the prognostic factors for colon cancer patients.Results The expression level of the lncRNA TPT1-AS1 was significantly higher(3.405±0.555 vs 1.766±0.096)and that of miR-30c-5p was significantly lower(0.306±0.146 vs 0.872±0.267)in colon cancer tissues than in adjacent tissues(P<0.05).The expression level of the lncRNA TPT1-AS1 was significantly higher in colon cancer TNM stageⅢ-Ⅳthan in stageⅠ-Ⅱ(3.651±0.579 vs 3.257±0.486),in T_(3)-T_(4)colon cancer than in T_(1)-T_(2)(3.523±0.601 vs 3.301±0.491),and in colon cancer with lymph node metastasis than in that without(3.614±0.585 vs 3.220±0.456)(P<0.05).The expression level of miR-30C-5P was significantly lower in colon cancer TNM stageⅢ-Ⅳthan that in stageⅠ-Ⅱ(0.251±0.126 vs 0.346±0.145),in T_(3)-T_(4)colon cancer than in T_(1)-T_(2)(0.270±0.119 vs 0.338±0.162),and in colon cancer with lymph node metastasis than in that without(0.255±0.125 vs 0.351±0.151)(P<0.05).Pearson correlation analysis showed that the expression of lncRNA1 TPT1-AS1 was negatively correlated with miR-30C-5P expression in colon cancer tissues(r=-0.572,P<0.05).Kaplan-Meier survival analysis showed that the 3-year cumulative survival rate(59.32%vs 87.93%)of the group with high lncRNA TPT1-AS1 expression was significantly lower than that of the group with low lncRNA1 TPT1-AS1 expression.The 3-year cumulative survival rate of the group with high miR-30C-5P expression(85.00%vs 61.40%)was significantly higher than that of the group with low miR-30C-5P expression(P<0.05).Multivariate Cox regression analysis showed that TNM stageⅢ-Ⅳ[hazard ratio(HR)=2.387,95%confidence interval(CI):1.004-5.671],lymph node metastasis(HR=2.667,95%CI:1.021-6.969),and TPT1-AS1≥3.405(HR=2.023,95%CI:1.076-3.803)were independent prognostic risk factors for colon cancer patients,while mir-30C-5p≥0.306(HR=0.175,95%CI:0.012-0.423)was an independent protective factor(P<0.05).Conclusion The expression of lncRNA1 TPT1-AS1 in colon cancer tissue is significantly up-regulated,and the expression of miR-30c-5p is significantly down-regulated,both of which are associated with TNM stage,depth of invasion and lymph node metastasis,are independent prognostic factors for patients,and may become markers for prognostic evaluation of colon cancer.