Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology.
Theranostics. 2019 Jan 25;9(4):920-931. doi: 10.7150/thno.30339. eCollection 2019.
Although serum microRNAs (miRNAs) are currently being considered as promising noninvasive biomarkers for cancers, their role in the prognosis of oral squamous cell carcinoma (OSCC) has not been elucidated. Here we aimed to identify serum miRNA biomarkers that could be used as prognosis predictors of OSCC. : A cohort of 260 serum miRNA samples was assessed in a three-step approach that included a screening stage, a training stage, and a testing stage. The correlation between prognosis of OSCC and the miRNAs expression was comprehensively analyzed. : A two-miRNA signature involving miR-626 and miR-5100 has been developed. Patients defined to be high-risk group by the two-miRNA signature had significantly shortened median survival time compared with the low-risk group. In multivariate analysis, this two-miRNA signature was independently predictive of survival, and achieved a superior predictive value compared with that of traditional clinicopathologic factors such as pathology grade as well as tumor and node metastasis (TNM) stage. An integrated prognostic model combining the TNM stage and miRNA signature displayed the highest prognostic performance (AUC value: 0.787, specificity: 0.884, sensitivity: 0.573) compared to the TNM stage-alone (AUC value: 0.630, specificity: 0.526, sensitivity: 0.733) or miRNA signature-alone model (AUC value: 0.771, specificity: 0.768, sensitivity: 0.773). In addition, we found that OSCC tumor cells not only expressed a high level of these two miRNAs, but also secreted certain miRNAs into the extracellular environment, suggesting these miRNAs may originate from tumor cells. : In our study, we established a two-miRNA signature that was strongly and independently associated with prognosis in OSCC, and may serve as a promising prognosis predictor.
虽然血清 microRNAs(miRNAs)目前被认为是癌症有前途的非侵入性生物标志物,但它们在口腔鳞状细胞癌(OSCC)预后中的作用尚未阐明。在这里,我们旨在确定可作为 OSCC 预后预测因子的血清 miRNA 生物标志物。
我们采用三步法评估了 260 个血清 miRNA 样本,包括筛选阶段、训练阶段和测试阶段。综合分析了 miRNA 表达与 OSCC 预后的相关性。
开发了一个涉及 miR-626 和 miR-5100 的两 miRNA 特征。通过两 miRNA 特征定义的高风险组患者的中位生存时间明显短于低风险组。在多变量分析中,该两 miRNA 特征独立预测生存,并且与传统临床病理因素(如病理分级以及肿瘤和淋巴结转移(TNM)分期)相比,具有更好的预测价值。与单独的 TNM 分期模型(AUC 值:0.630,特异性:0.526,敏感性:0.733)相比,结合 TNM 分期和 miRNA 特征的综合预后模型显示出最高的预后性能(AUC 值:0.787,特异性:0.884,敏感性:0.573)。
此外,我们发现 OSCC 肿瘤细胞不仅表达高水平的这两个 miRNA,而且还将某些 miRNA 分泌到细胞外环境中,表明这些 miRNA 可能源自肿瘤细胞。
在我们的研究中,我们建立了一个与 OSCC 预后强烈且独立相关的两 miRNA 特征,可能作为一种有前途的预后预测因子。