Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
Oncology Department, The Second Hospital of Nanjing, Nanjing, China.
Sci Rep. 2024 Jun 11;14(1):13367. doi: 10.1038/s41598-024-64197-z.
Patients with distant metastasis of head and neck squamous cell carcinoma (HNSCC) often have a poor prognosis. However, early diagnosis of distant metastasis is challenging in clinical practice, and distant metastasis is often only detected in the late stages of tumor metastasis through imaging techniques. In this study, we utilized data from HNSCC patients collected from the TCGA database. Patients were divided into distant metastasis and nonmetastasis groups based on the tumor-node-metastasis (TNM) stage. We analyzed the differentially expressed genes between the two groups (DM/non-M DEGs) and their associated lncRNAs and generated a predictive model based on 23 lncRNAs that were significantly associated with the occurrence of distant metastasis in HNSCC patients. On this basis, we built a nomogram to predict the distant metastasis of HNSCC patients. Moreover, through WGCNA and Cytoscape software analysis of DM/non-M DEGs, we identified the gene most closely related to HNSCC distant metastasis: EIF5A. Our findings were validated using GEO data; EIF5A expression was significantly increased in the tumor tissues of HNSCC patients with distant metastasis. We then predicted miRNAs that can directly bind to EIF5A via the TargetScan and miRWalk websites, intersected them with differentially expressed miRNAs in the two groups from the TCGA cohort, and identified the only overlapping miRNA, miR-424; we predicted the direct binding site of EIF5A and miR-424 via the miRWalk website. Immunohistochemistry further revealed high expression of EIF5A in the primary tumor tissue of HNSCC patients with distant metastasis. These results provide a new perspective for the early diagnosis of distant metastasis in HNSCC patients and the study of the mechanisms underlying HNSCC distant metastasis.
患有头颈部鳞状细胞癌(HNSCC)远处转移的患者通常预后较差。然而,在临床实践中,远处转移的早期诊断具有挑战性,并且通常只有通过影像学技术才能在肿瘤转移的晚期发现远处转移。在这项研究中,我们利用了来自 TCGA 数据库的 HNSCC 患者的数据。根据肿瘤-淋巴结-转移(TNM)分期,将患者分为远处转移和非转移组。我们分析了两组之间差异表达的基因(DM/non-M DEGs)及其相关的 lncRNA,并基于与 HNSCC 患者远处转移发生显著相关的 23 个 lncRNA 生成了一个预测模型。在此基础上,我们构建了一个列线图来预测 HNSCC 患者的远处转移。此外,通过 WGCNA 和 Cytoscape 软件对 DM/non-M DEGs 进行分析,我们确定了与 HNSCC 远处转移最密切相关的基因:EIF5A。我们的研究结果通过 GEO 数据得到了验证;EIF5A 在 HNSCC 伴有远处转移的肿瘤组织中的表达明显增加。然后,我们通过 TargetScan 和 miRWalk 网站预测可以直接与 EIF5A 结合的 miRNAs,将它们与 TCGA 队列中两组之间差异表达的 miRNAs 进行交集,并确定了唯一重叠的 miRNA,miR-424;我们通过 miRWalk 网站预测了 EIF5A 和 miR-424 的直接结合位点。免疫组织化学进一步揭示了在伴有远处转移的 HNSCC 患者的原发肿瘤组织中 EIF5A 的高表达。这些结果为 HNSCC 患者远处转移的早期诊断以及 HNSCC 远处转移机制的研究提供了新的视角。