Serum miR-626 and miR-5100 are Promising Prognosis Predictors for Oral Squamous Cell Carcinoma
Serum miR-626 and miR-5100 are Promising Prognosis Predictors for Oral Squamous Cell Carcinoma
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血清 miR-626 和 miR-5100 是口腔鳞状细胞癌有希望的预后预测因子
DOI：
10.7150/thno.30339
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发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Xu, Qin
中科院分区：
文献类型：
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作者：
Shi, Jianbo;Bao, Xin;Xu, Qin
虽然血清microRNAs （miRNAs）目前被认为是一种很有前途的非侵入性癌症生物标志物，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，我们的目的是鉴定血清miRNA生物标志物，可作为OSCC的预后预测指标。方法：对260个血清miRNA样本进行三步评估，包括筛选阶段、训练阶段和测试阶段。综合分析OSCC预后与miRNAs表达的相关性。结果：已经开发了涉及miR-626和miR-5100的双mirna签名。通过双mirna标记定义为高危组的患者与低危组相比，中位生存时间明显缩短。在多变量分析中，这两个mirna标记可以独立预测生存，与传统的临床病理因素（如病理分级、肿瘤和淋巴结转移（TNM）分期）相比，具有更高的预测价值。与单纯TNM分期（AUC值：0.630，特异性：0.526，敏感性：0.733）或单纯miRNA特征模型（AUC值：0.771，特异性：0.768，敏感性：0.773）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表现（AUC值：0.787，特异性：0.884，敏感性：0.573）。此外，我们发现OSCC肿瘤细胞不仅高水平表达这两种mirna，而且在细胞外环境中分泌一定的mirna，提示这些mirna可能来源于肿瘤细胞。结论：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双mirna特征，并可能作为一个有希望的预后预测指标。
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.Methods: 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.Results: 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.Conclusion: 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.