lncRNA SNHG4与miR-148a在肝癌患者中的表达及其对预后的影响

Expression and prognosis of lncRNA SNHG4 and miR-148a in hepatocellular carcinoma

目的 探讨长链非编码RNA(long non-coding RNA,lncRNA)核仁小RNA宿主基因4(small nucleolar RNA host gene 4,SNHG4)与微小核糖核酸-148a(miR-148a)在肝癌患者中的表达量,并分析二者与预后的关系。方法 选取2016年9月—2019年4月河北省秦皇岛市第一医院收治的161例肝癌患者为研究对象,取肝癌组织、癌旁组织检测lncRNA SNG4、miR-148a表达水平,观察二者与肝癌病理特征的关系。随访24个月,记录患者的累积生存情况,并分成生存组与死亡组,比较两组lncRNA SNHG4、miR-148a表达水平,利用Pearson线性相关分析二者相关性,绘制受试者工作特征曲线(receiver operating characteristic curve,ROC)分析二者评估肝癌预后的曲线下面积(area under the curve,AUC)。结果 患者肝癌组织中lncRNA SNHG4相对表达量高于癌旁组织[(7.93±2.15)vs(2.01±0.76),t=32.940,P<0.01]。肝癌组织中miR-148a相对表达量低于癌旁组织[(0.64±0.27)vs(1.37±0.31),t=22.532,P<0.01]。同lncRNA SNHG4低表达(lncRNA SNHG4<7.93)组比较,lncRNA SNHG4高表达(lncRNA SNHG4≥7.93)组肿瘤≥5 cm(56.82%vs 34.25%,χ^(2)=8.170,P=0.004)、肝内转移(32.95%vs 10.96%,χ^(2)=10.906,P=0.001)、临床分期Ⅲ期(42.04%vs 13.70%,χ^(2)=19.412,P<0.01)、低分化(39.68%vs 6.85%,χ^(2)=14.231,P<0.01)、多发肿瘤(56.82%vs 26.03%,χ^(2)=15.447,P<0.01)、微血管侵犯(32.95%vs 12.33%,χ^(2)=9.414,P=0.002)所占比例均高于lncRNA SNHG4低表达组。同miR-148a高表达(miR-148a≥0.64)组比较,miR-148a低表达(miR-148a<0.64)组肿瘤最大径≥5 cm(58.44%vs 35.71%,χ^(2)=8.339,P=0.004)、肝内转移(35.06%vs 11.90%,χ^(2)=12.175,P<0.01)、临床分期Ⅲ期(40.26%vs 19.05%,χ^(2)=16.284,P<0.01)、低分化(27.27%vs 13.10%,χ^(2)=5.071,P=0.024)、多发肿瘤(58.44%vs 28.57%,χ^(2)=14.636,P<0.01)、微血管侵犯(33.77%vs 14.29%,χ^(2)=8.455,P=0.004)所占比例均高于miR-148a高表达组。随访24个月内,死亡30例,占18.63%,生存组lncRNA SNHG4相对表达量低于死亡组[(7.53±0.95)vs(9.68±0.40),t=12.128,P<0.01]。生存组miR-148a相对表达量高于死亡组[(0.68±0.23)vs(0.45±0.08),t=5.392,P<0.01]。Pearson相关分析提示肝癌患者lncRNA SNHG4与miR-148a表达成负相关(r=-0.746,P<0.01)。肝癌组织中lncRNA SNHG4、miR-148a表达量单独与联合评估肝癌预后的AUC分别为0.784、0.770、0.888。结论 肝癌组织中lncRNA SNHG4呈过表达,miR-148a表达则降低,二者表达成负相关,且均对预后评估有一定价值。

Objective To study the expression and prognostic value of long non-coding RNA(lncRNA)of the small nucleolar RNA host gene 4(SNHG4)and microribonucleic acid-148a(miR-148a)in liver cancer.Methods A total of 161liver cancer patients were admitted from September 2016to April 2019in the the First Hospital of Qinhuangdao City as the research subjects.Liver cancer tissues and adjacent tissues were collected to detect the expression levels of LncRNA SNHG4and miR-148a.The correlation with the pathological characteristics of liver cancer was analyzed.With 24months follow up study,the patients were divided into two groups(survival group and death group)according to the cumulative survival situation.The expression levels of LncRNA SNHG4and miR-148abetween the two groups were compared.Pearson linear correlation was used to analyze the correlation,receiver operating characteristic curve(ROC)was drawn to assess the prognosis of liver cancer. Results The relative expression level of lncRNA SNHG4in liver cancer tissues was higher than that in the adjacent tissues(7.93±2.15 vs 2.01±0.76,t=32.940,P<0.01).The relative expression level of miR-148ain liver cancer tissues was lower than that in the adjacent tissues(0.64±0.27 vs1.37±0.31,t=22.532,P<0.01).In the lncRNA SNHG4high expression group,the largest tumor diameter≥5cm(56.82%vs 34.25%,χ^(2)=8.170,P=0.004),intrahepatic metastasis(32.95% vs 10.96%,χ^(2)=10.906,P=0.001),clinical stageⅢ (42.04% vs 13.70%,χ^(2)=19.412,P<0.01),poorly differentiated(39.68% vs 6.85%,χ^(2)=14.231,P<0.01),multiple tumors(56.82% vs 26.03%,χ^(2)=15.447,P<0.01),and microvascular invasion(32.95%vs 12.33%,χ^(2)=9.414,P=0.002)were higher than those in the lncRNA SNHG4low expression group.In the low expression group of miR-148a,the largest tumor diameter≥5cm(58.44% vs 35.71%,χ2=8.339,P =0.004),intrahepatic metastasis(35.06% vs11.90%,χ^(2)=12.175,P<0.01),clinical stageⅢ (40.24% vs 19.05%,χ^(2)=16.284,P<0.01),poorly differentiated(27.27%vs 13.10%,χ2=5.071,P=0.024),multiple tumors(58.44% vs 28.57%,χ^(2)=14.636,P<0.01)and microvascular invasion(33.77% vs 14.28%,χ^(2)=8.455,P=0.004)were higher than those in the miR-148ahigh expression group.Within 24months of follow-up,30cases died,accounting for 18.63%.The relative expression level of lncRNA SNHG4in the survival group was lower than that in the death group(7.53±0.95 vs 9.68±0.40,t=12.128,P<0.01).The relative expression level of miR-148ain the survival group was higher than that in the death group(0.68±0.23 vs 0.45±0.08,t=5.392,P<0.01).Pearson linear correlation analysis indicated that the expression of LncRNA SNHG4and miR-148ain liver cancer patients was negatively correlated(r=-0.746,P<0.01).The AUC of lncRNA SNHG4 and miR-148 aexpression in liver cancer tissues alone and in combination to assess the prognosis of liver cancer were0.784,0.770,0.888,respectively. Conclusions LncRNA SNHG4is overexpressed in liver cancer tissues,while the expression of miR-148ais decreased.The expressions of both lncRNA SNHG4and miR-148aare negatively correlated.