Shu Tingting, Wang Xudong
Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin, 300060, China.
Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
Heliyon. 2023 May 3;9(5):e15494. doi: 10.1016/j.heliyon.2023.e15494. eCollection 2023 May.
Head and neck squamous carcinomas (HNSC) are the seventh most common cancer around the world. Treatment options available today have considerable limitations in terms of efficacy. Identifying novel therapeutic targets for HNSC is, therefore, urgently needed. As a novel determined regulated cell death (RCD), Cuproptosis is correlated with the development, treatment response, and prognosis of various cancer. However, the potential role of Cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of HNSC remains unclear. To figure out whether TME cells and Cuproptosis could better predict prognosis, in this study, we analyzed the expression, mutation status, and other clinical information of 502 HNSC patients by dividing them into four clusters based on their CRGs and TME cell expression. Utilizing the LASSO-Cox method and bootstrap, we established Prognostic Cuproptosis and TME classifier, which were significantly associated with prognosis, pathways, clinical features, and immune cell infiltration in TME of HNSC. To go further, the subgroup Cup low/TMEhigh displayed a better prognosis than any others. Two GEO datasets demonstrated the proposed risk model's clinical applicability. Our GO enrichment analyses proved the conjoint effect of Cuproptosis and TME on tumor angiogenesis, proliferation, and so on. Single-cell analysis and Immunotherapy profile then provided a foundation for determining the molecular mechanisms. It revealed the prognostic risk score positively correlated with T cell activation and natural killer (NK) recruiting. As far as we know, this study is the first time to explore the involvement of CRGs regulation in the TME of HNSC. In a word, it is vital to use these findings to develop new therapeutic strategies.
头颈部鳞状细胞癌（HNSC）是全球第七大常见癌症。目前可用的治疗方案在疗效方面有相当大的局限性。因此，迫切需要确定HNSC的新型治疗靶点。作为一种新确定的调节性细胞死亡（RCD），铜死亡与各种癌症的发生发展、治疗反应及预后相关。然而，铜死亡相关基因（CRG）在HNSC肿瘤微环境（TME）中的潜在作用仍不清楚。为了弄清楚TME细胞和铜死亡是否能更好地预测预后，在本研究中，我们根据CRG和TME细胞表达将502例HNSC患者分为四个簇，分析了他们的表达、突变状态及其他临床信息。利用LASSO - Cox方法和自助法，我们建立了预后铜死亡和TME分类器，其与HNSC的预后、通路、临床特征及TME中的免疫细胞浸润显著相关。进一步研究发现，Cup低/TME高亚组的预后优于其他任何亚组。两个GEO数据集证明了所提出的风险模型的临床适用性。我们的GO富集分析证明了铜死亡和TME对肿瘤血管生成、增殖等的联合作用。单细胞分析和免疫治疗图谱随后为确定分子机制提供了基础。结果显示预后风险评分与T细胞活化和自然杀伤（NK）细胞募集呈正相关。据我们所知，本研究首次探讨了CRG调控在HNSC的TME中的作用。总之，利用这些发现来制定新的治疗策略至关重要。
