长链非编码RNA GAS8-AS1与微小RNA 135b在肝细胞癌中的表达及临床意义

Expressions of long noncoding GAS8-AS1 and microRNA 135b in hepatocellular carcinoma and their clinical significance

背景和目的:大量研究表明,长链非编码RNA (lncRNA)与微小RNA (miRNA)及其靶基因之间内源性竞争的调控模式与恶性肿瘤的发生发展密切相关。笔者团队前期通过软件预测发现,lncRNA GAS8-AS1和miR-135b之间存在结合位点,但两者在肝细胞癌(HCC)中是否存在竞争关系及其作用尚不清楚。因此,本研究探讨lncRNA GAS8-AS1和miR-135b在HCC组织中的表达及其临床意义。方法:收集2017年2月—2019年2月在青海大学附属医院行手术切除的110例HCC患者的癌组织及癌旁组织标本,通过qRT-PCR检测lncRNA GAS8-AS1和miR-135b的表达,分析两者与患者临床病理特征及预后的关系。结果:lncRNA GAS8-AS1在HCC组织中的表达明显低于癌旁组织,而miR-135b在HCC组织中的表达明显高于癌旁组织(均P<0.05)。两者的表达水平均与HCC患者的Edmondson分期、TNM分期、分化程度及淋巴结转移情况有关(均P<0.05)。lncRNA GAS8-AS1低表达患者与miR-135b高表达患者的3年总生存率分别明显低于lncRNA GAS8-AS1高表达患者与miR-135b低表达患者(均P<0.05)。lncRNA GAS8-AS1低表达、miR-135b高表达以及高Edmondson分级、高TNM分期、有乙肝病史是影响HCC患者预后的独立危险因素(均P<0.05)。结论:在HCC组织中lncRNA GAS8-AS1低表达,miR-135b高表达,两者表达水平的消长可能与HCC的发生发展以及患者的预后密切相关。

Background and Aims: Many studies have demonstrated that the regulation mode of endogenous competition between the long noncoding RNAs(lncRNAs) and the microRNAs(miRNAs), as well as their target genes, is closely related to the occurrence and development of malignant tumors. The authors’ team has previously found a binding site between lncRNA GAS8-AS1 and miR-135b through software prediction. However, it is unclear whether there is competition between them in hepatocellular carcinoma(HCC) and their actions. Therefore, this study aims to investigate the expressions of lncRNA GAS8-AS1 and miR-135b in HCC tissue and their clinical significance.Methods: The specimens of cancer and adjacent tissues from 110 patients with HCC undergoing surgical resection in Qinghai University Affiliated Hospital from February 2017 to February 2019 were collected. qRT-PCR was used to detect the expressions of lncRNA GAS8-AS1 and miR-135b, and their associations with clinicopathologic features and the prognosis of patients were analyzed.Results: The expression of lncRNA GAS8-AS1 in HCC tissue was significantly lower, while the expression of miR-135b was significantly higher in HCC tissue than in paracancerous tissue(both P<0.05). Their expression levels were all related to the Edmondson stage, TNM stage, degree of differentiation and lymph node metastasis in HCC patients(all P<0.05). The 3-year overall survival rate of patients with low expression of lncRNA GAS8-AS1 or high expression of miR-135b was significantly lower than that of patients with high expression of lncRNA GAS8-AS1 or low expression of miR-135b, respectively(both P<0.05). Low expression of lncRNA GAS8-AS1 and high expression of miR-135b together with high Edmondson grade, advanced TNM stage, and history of hepatitis B were independent risk factors for the prognosis of HCC patients(all P<0.05).Conclusion: There is low expression of lncRNA GAS8-AS1 and high expression of miR-135b in HCC tissue, and the competitive state of their expressions may be closely associated with the initiation and progression of HCC as well as the prognosis of patients.