血清microRNA-618表达与原发性肝癌疗效及预后的关系

Relationship of serum microRNA-618 with therapeutic effect and prognosis of primary hepatic cancer

摘要:

目的 探讨血清microRNA-618（miR-618）表达与原发性肝癌（PHC）疗效及预后的关系。方法 选取2016年2月—2018年3月在内江市第二人民医院接受治疗的65例PHC患者为病例组，另选取同期65例健康体检者为健康组。通过实时荧光定量聚合酶链反应（qRT-PCR）检测miR-618 mRNA相对表达量，分析miR-618表达与PHC患者临床病理特征的关系；根据患者miR-618 mRNA相对表达量分为高表达组和低表达组，比较两组治疗后血清甲胎蛋白（AFP）、甲胎蛋白异质体（AFP-L3）、磷脂酰肌醇蛋白聚糖-3（GPC3）、高尔基体蛋白-73（GP73）水平及平均疾病进展时间（TTP）和中位生存期（MST），分析miR-618表达与PHC患者治疗后血清肿瘤标志物水平及预后的关系。结果 病例组治疗前血清miR-618 mRNA相对表达量（0.72±0.21）比健康组（1.03±0.43）低（P <0.05）；病例组治疗后血清miR-618 mRNA相对表达量（0.83±0.19）比治疗前（0.72±0.21）高（P <0.05）；病例组不同性别、年龄、肿瘤直径、Child-pugh分级、是否伴有肝硬化及是否有癌栓患者的血清miR-618 mRNA相对表达量比较，差异无统计学意义（P >0.05）；低表达组miR-618 mRNA相对表达量比高表达组低（P <0.05），AFP-L3、AFP、GPC3、GP73水平比高表达组高（P <0.05）；Pearson相关性分析显示，血清miR-618 mRNA相对表达量与血清AFP-L3水平（r =-0.453）、AFP水平（r =-0.568）、GPC3水平（r =-0.412）、GP73水平（r =-0.612）呈负相关（P <0.05）；低表达组TTP（13.97±1.76）个月、MST（21.98±3.06）个月比高表达组TTP（25.13±2.25）个月、MST（34.06±4.19）个月低（P <0.05）。结论 miR-618在PHC中表达下调，其表达与治疗后的血清肿瘤标志物水平及预后相关，可能成为PHC诊断、治疗及预后评估的新生物学标志物。

Abstract:

Objective To analyze the relationship between serum microRNA-618 (miR-618) level with the therapeutic effect and prognosis of primary hepatic cancer (PHC).Methods From February 2016 to March 2018, 65 patients with PHC who received Hifu combined with TACE treatment in the second people's Hospital of Neijiang were enrolled into the case group, and another 65 patients who received physical examination in the same period were enrolled into the health group. The relative expression of miR-618 was measured by real-time fluorescent quantitative PCR (qRT-PCR), and the relationship between miR-618 and the clinical characteristics of PHC patients was analyzed; according to the relative expression of miR-618, it was divided into high expression group and low expression group, and the two groups were compared serum tumor marker levels after treatment [alpha-fetoprotein (AFP), alpha-fetoprotein heterogene (AFP-L3), glypican-3 (GPC3), Golgi protein-73 (GP73)], and the mean time to disease progression (TTP) and median survival time (MST) were analyzed to analyze the relationship between the serum tumor marker levels and prognosis of miR-618 and HIFU combined with TACE treatment.Results The relative expression level of serum miR-618 in the case group before treatment (0.72 ± 0.21) was lower than that in the healthy group (1.03 ± 0.43) (P < 0.05); the relative expression level of serum miR-618 in the case group after treatment (0.83 ± 0.19) was higher than that before treatment (0.72 ± 0.21) (P < 0.05); the relative expression of miR-618 in serum of patients with different sex, age, tumor diameter, Child-pugh grade, cirrhosis, and tumor thrombus was not significant (P > 0.05). MiR-618 in low expression group was lower than that in high expression group (P < 0.05), and AFP-L3, AFP, GPC3, GP73 were higher than that in high expression group (P < 0.05); Serum miR-618 level was negatively correlated with serum AFP-L3 level (r = -0.453), AFP level (r = -0.568), GPC3 level (r = -0.412), GP73 level (r = -0.612) (P < 0.05).Conclusion The expression of miR-618 is down-regulated in PLC, and its expression is closely related to the level of serum tumor markers and prognosis after treatment. It may become a new biomarker for the diagnosis, treatment and prognosis evaluation of PHC.