喉鳞状细胞癌（LSCC）是人类头颈部常见的癌症。LSCC患者的5年生存率在过去四十年中有所下降。研究报告显示，微小RNA（miRNA）能够预测不同癌症患者的预后结果。然而，关于使用多miRNA模型作为LSCC诊断或预后的标志物方面尚无报道。为建立与miRNA表达相关的LSCC患者诊断、预测和辅助治疗模型，本研究分别入组了107例临床LSCC患者，并从TCGA数据库获取了117个LSCC样本数据进行评估。接下来，依次进行了下一代测序（NGS）、原始数据处理、最小绝对值收缩和选择操作算法、Cox回归分析、诊断模型构建和细胞功能实验（包括增殖、迁移和侵袭实验）。 与正常组织相比，LSCC中miRNA表达发生明显失调。建立了由miR-137-3p、miR-3934-5p、miR-1276、miR-129-5p、miR-7-5p和miR-105-5p共同组成的六miRNA预后模型用于LSCC患者的预测。六miRNA预后模型与LSCC患者的整体生存率（OS，p = 2.5e-05，HR: 4.30 [2.20-8.50]）、无进展生存期（PFI，p = 0.025，HR: 1.94 [1.08-3.46]）和疾病特定生存期（DSS，p = 1.1e-05，HR: 5.00 [2.50-10.00]）密切相关。还基于六miRNA预后模型和临床特征构建了预测2年、3年和5年整体生存率的诊断模型。此外，阻断六个miRNA之一的功能可以抑制LSCC细胞的增殖、侵袭和迁移。 本研究中六miRNA预后模型的性能显示了其对于LSCC进展评估的显著潜力。此外，六miRNA预后模型在临床中可能作为预后和治疗靶点的预测工具。© 2023作者

Laryngeal squamous cell carcinoma (LSCC) is a common cancer of the head and neck in humans. The 5-years survival rate of patients with LSCC have declined in the past four decades. microRNAs (miRNAs) has been reported to be capable of predicting the prognosis outcomes of patients with different cancers. However, there are no reports on the usage of multi-miRNAs model as signature for the diagnosis or prognosis of LSCC.To establish the miRNAs expression-associated model for diagnosis, prognosis prediction and aided therapy of patients with LSCC, the present study enrolled 107 patients with LSCC in clinic and obtained 117 LSCC samples data from TCGA database for evaluation, respectively. Next generation sequencing (NGS), raw data processing, the least absolute shrinkage and selection operator algorithm, Cox regression analysis, construction of nomogram and cell function assays (including proliferation, migration and invasion assays) were sequentially performed.There were massively dysregulated miRNAs in the LSCC compared to normal tissues. A six-miRNAs signature consists of miR-137-3p, miR-3934-5p, miR-1276, miR-129-5p, miR-7-5p and miR-105-5p was built for prognosis prediction of LSCC patients. The six-miRNAs signature is strongly associated with the poor overall survival (OS, p = 2.5e-05, HR: 4.30 [2.20-8.50]), progression free interval (PFI, p = 0.025, HR: 1.94 [1.08-3.46]) and disease specific survival (DSS, p = 1.1e-05, HR: 5.00 [2.50-10.00]). A nomogram for prediction of 2-, 3- and 5-years OS was also developed based on the six-miRNAs signature and clinical features. Furthermore, blocking the function of each of the six miRNAs inhibited proliferation, invasion and migration of LSCC cells.The performance of six-miRNAs signature described in the current study demonstrated remarkable potential for progression assessment of LSCC. Moreover, the six-miRNAs signature may serve as predictive tool for prognosis and therapeutic targets of LSCC in clinic.© 2023 The Authors.