MicroRNA-223表达与肝癌根治性切除术预后的相关性

Value of miRNA-223 expression in predicting outcome of hepatocellular carcinoma after radical therapy

摘要:

 摘要：目的  识别可以作为肝癌根治性切除术患者预后标志物的microRNA（miRNA）分子。方法  利用miRNA微阵列方法对2例原发性肝癌及对应的肺转移性肝癌进行miRNA表达分析。将原发性和转移性肝癌中表达量有2倍差异的miRNAs作为候选miRNAs分子。在miRNA验证过程中，运用实时荧光定量聚合酶链反应（qRT-PCR）分析37例肝癌及相应癌旁非肿瘤组织中候选miRNAs分子的表达，并将其与患者的临床病理特征及生存情况进行相关性分析。结果  最终选取8种miRNAs（miR-27b、122、142-5p、196a、223、590-5p、630及944）作为候选miRNA。只有miR-223表达水平与肿瘤分期、有丝分裂指数相关。将肝癌患者分为miR-223高表达组（25例）和miR-223低表达组（12例）后发现，miR-223高表达与较高T分期、淋巴结转移、较高丝分裂指数及较高Ki-67阳性指数相关。此外，miR-223高表达还与总体生存率和无病存活率下降相关（P <0.05），中位随访时间37.9个月[疾病复发危险比为16.267（95%CI：1.732，153.789）P =0.015]。结论  肝癌组织中miR-223异常表达与肝癌患者治疗结束后发生复发转移，以及无病生存时间和总生存率有关，通过检测肿瘤组织中miR-223 qRT-PCR反应有可能预测患者预后。

Abstract:

Abstract: Objective To identify miRNAs that could be potential prognostic biomarkers of hepatocellular carcinoma in patients who underwent radical resection. Methods For miRNA target screening, 2 primary HCC and the corresponding liver metastases were screened for miRNA expression by the miRNA Chip analysis. Candidate miRNAs were selected by more than 2-fold difference of expression between metastatic and primary tumors. For miRNA target validation, qRT-PCR was performed for candidate miRNAs on 37 HCC and the matched paracancerous non-tumor tissues, and the correlations of the miRNA levels with the clinicopathological features and survival were analyzed. Results Eight miRNAs (miRNA-27b, 122, 142-5p, 196a, 223, 590-5p, 630, and 944) were selected as candidate miRNAs. Only miR-223 level was significantly associated with tumor stage and mitotic count. When the HCC patients were stratified into high (25 cases) and low (12 cases) miRNA-
223 expression groups, high miRNA-223 expression was associated with advanced T stage, lymphatic metastasis, higher mitotic counts, and higher Ki-67-labeling index. In addition, high miRNA-223 expression was associated with decreased overall survival and tumor-free survival (P < 0.05) during a median followup of 37.9 months [the hazard ratio for recurrence = 16.267 (95% CI: 1.732, 153.789), P = 0.015]. Conclusions High miRNA-223 expression has a significant relation with poor outcome of patients with HCC.