Zhang Linshi, Zhang Zhe, Zheng Xiwang, Lu Yan, Dai Li, Li Wenqi, Liu Hui, Wen Shuxin, Xie Qiuping, Zhang Xiangmin, Wang Ping, Wu Yongyan, Gao Wei
Department of Thyroid Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, PR China.
Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China.
Noncoding RNA Res. 2023 Aug 4;8(4):550-561. doi: 10.1016/j.ncrna.2023.08.001. eCollection 2023 Dec.
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.
喉鳞状细胞癌（LSCC）是人类常见的头颈部癌症。在过去的四十年中，LSCC患者的5年生存率有所下降。据报道，微小RNA（miRNA）能够预测不同癌症患者的预后结果。然而，尚无关于使用多miRNA模型作为LSCC诊断或预后标志物的报道。
为建立用于LSCC患者诊断、预后预测和辅助治疗的miRNA表达相关模型，本研究纳入了107例临床LSCC患者，并分别从TCGA数据库获得117例LSCC样本数据进行评估。依次进行了下一代测序（NGS）、原始数据处理、最小绝对收缩和选择算子算法、Cox回归分析、列线图构建及细胞功能测定（包括增殖、迁移和侵袭测定）。
与正常组织相比，LSCC中存在大量失调的miRNA。构建了一个由miR-137-3p、miR-3934-5p、miR-1276、miR-129-5p、miR-7-5p和miR-105-5p组成的六miRNA标志物，用于预测LSCC患者的预后。该六miRNA标志物与较差的总生存期（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]）和疾病特异性生存期（DSS，p = 1.1e-05，HR：5.00 [2.50 - 10.00]）密切相关。还基于该六miRNA标志物和临床特征开发了一个预测2年、3年和5年OS的列线图。此外，阻断六种miRNA中每一种的功能均抑制了LSCC细胞的增殖、侵袭和迁移。
本研究中描述的六miRNA标志物在LSCC进展评估方面显示出显著潜力。此外，该六miRNA标志物可作为临床中LSCC预后的预测工具和治疗靶点。
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