pⅢ期非小细胞肺癌中miR-155的表达与预后关系的研究

Association of MiR-155 Expression with Prognosis in Resected Stage Ⅲ Non-small Cell Lung Cancer

背景与目的 pIII期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者5年生存率低于25%,需要寻找新的预后标志物,指导患者个体化治疗。MiR-155在许多肿瘤中表达上调,并对肿瘤有广泛的调控作用。本研究旨在探讨手术切除的pIII期NSCLC中miR-155的表达与预后的关系。方法采用qRT-PCR法检测162例pIII期NSCLC手术患者福尔马林固定石蜡包埋组织(formalin-fixed,paraffin-embedded,FFPE)中miR-155的表达。结果 miR-155在pIII期NSCLC中表达与淋巴结转移程度正相关(r=0.169,P=0.032)。单因素生存分析显示在总体队列(P<0.001)、鳞癌亚组(P=0.002)、腺癌亚组(P=0.003)中,miR-155高表达组的总体生存期(overall survival,OS)均低于miR-155低表达组。根据淋巴结转移程度分层分析显示在N0-1亚组中,miR-155高表达和低表达组间OS无统计学差异(P=0.319),在N2的患者中,miR-155高表达组OS显著低于miR-155低表达组(P<0.001)。多因素生存分析显示miR-155高表达是影响患者预后的独立危险因素(RR=2.311,95%CI:1.479-3.611,P<0.001)。结论 miR-15高表达不利于手术切除的pIII期NSCLC患者的总体生存,并且与淋巴结转移度正相关。MiR-155可作为评价pIII期NSCLC预后的生物标志物。

Background and objective Despite undergoing curative resection, the 5-year survival rate for stage III non-small cell lung cancer （NSCLC） patients is less than 25%. hTere is a need for biomarkers for prediction of survival and guiding individual therapy. MiR-155 is one of most commonly upregulated miRNAs in malignancies, and regulates multiple pro-oncogenic pathways. We aimed to investigate the prognostic impact of miR-155 in resected stage III NSCLC patients. Methods Tumor formalin-ifxed, paraffn-embedded （FFPE） from 162 resected stage III NSCLC patients were collected. Total RNA including miRNA was extracted, and qRT-PCR was used to determine the expression of miR-155. Results Spearman rank correlation test showed a positive correlation between miR-155 expression and nodal status （r=0.169, P=0.032）. MiR-155 expression had a signiifcant prognostic impact in the total cohort （P〈0.001）, in squamous cell carcinomas （P=0.002） and in adenocarcinomas （P=0.003）. In N0-1 subgroup, miR-155 expression did not have a signiifcant prognostic on overall survival in univariate analysis （P=0.319）. In N2 subgroup, miR-155 had a negative prognostic effect on OS in univariate analysis （P〈0.001）. Cox regression analysis revealed that miR-155 expression was unfavorable prognostic factors of OS （RR=2.311, 95%CI：1.479-3.611, P〈0.001）. Conclusion High expression of miR-155 represents a valuable marker of poor clinical outcomes in patients with stage III NSCLC.