Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
'Angelo Nocivelli' Institute of Molecular Medicine, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy.
Theranostics. 2021 Jan 1;11(6):2987-2999. doi: 10.7150/thno.45157. eCollection 2021.
Survival rates of oral squamous cell carcinoma (OSCC) remained substantially unchanged over the last decades; thus, additional prognostic tools are strongly needed. Salivary miRNAs have emerged as excellent non-invasive cancer biomarker candidates, but their association with OSCC prognosis has not been investigated yet. In this study, we analyzed global salivary miRNA expression in OSCC patients and healthy controls, with the aim to define its diagnostic and prognostic potential. Saliva was collected from patients with newly diagnosed untreated primary OSCC and healthy controls. Global profiling of salivary miRNAs was carried out through a microarray approach, while signature validation was performed by quantitative real-time PCR (RT-qPCR). A stringent statistical approach for microarray and RT-qPCR data normalization was applied. The diagnostic performance of miRNAs and their correlation with OSCC prognosis were comprehensively analyzed. In total, 25 miRNAs emerged as differentially expressed between OSCC patients and healthy controls and, among them, seven were significantly associated with disease-free survival (DFS). miR-106b-5p, miR-423-5p and miR-193b-3p were expressed at high levels in saliva of OSCC patients and their combination displays the best diagnostic performance (ROC - AUC = 0.98). Moreover, high expression of miR-423-5p was an independent predictor of poor DFS, when included in multivariate survival analysis with the number of positive lymph nodes - the only significant clinical prognosticator. Finally, we observed a significant decrease in miR-423-5p expression in matched post-operative saliva samples, suggesting its potential cancer-specific origin. Salivary miRNAs identified in our cohort of patients show to be accurate in OSCC detection and to effectively stratify patients according to their likelihood of relapse. These results, if validated in an independent set of patients, could be particularly promising for screening/follow-up of high-risk populations and useful for preoperative prognostic assessment.
口腔鳞状细胞癌 (OSCC) 的生存率在过去几十年中没有明显变化；因此，强烈需要额外的预后工具。唾液 microRNA 已成为优秀的非侵入性癌症生物标志物候选物，但它们与 OSCC 预后的关系尚未得到研究。在这项研究中，我们分析了 OSCC 患者和健康对照者的唾液全谱 microRNA 表达，旨在定义其诊断和预后潜力。收集了新诊断的未经治疗的原发性 OSCC 患者和健康对照者的唾液。通过微阵列方法进行唾液 microRNA 全谱分析，通过定量实时 PCR (RT-qPCR) 进行特征验证。应用严格的微阵列和 RT-qPCR 数据归一化统计方法。全面分析了 microRNA 的诊断性能及其与 OSCC 预后的相关性。总共 25 个 microRNA 在 OSCC 患者和健康对照者之间表达差异，其中 7 个与无病生存率 (DFS) 显著相关。miR-106b-5p、miR-423-5p 和 miR-193b-3p 在 OSCC 患者的唾液中表达水平较高，它们的组合显示出最佳的诊断性能 (ROC-AUC=0.98)。此外，miR-423-5p 高表达是多变量生存分析中淋巴结阳性数的独立预后因素，也是唯一有意义的临床预后因素。最后，我们观察到匹配的术后唾液样本中 miR-423-5p 表达显著降低，提示其具有潜在的肿瘤特异性来源。我们的患者队列中鉴定的唾液 microRNA 不仅在 OSCC 检测中准确，而且能够根据患者复发的可能性对患者进行有效分层。如果在独立患者组中得到验证，这些结果可能对高危人群的筛查/随访特别有希望，并且对术前预后评估也有用。
