Department of Otolaryngology - Head & Neck Surgery, School of Medicine, Kyung Hee University, Seoul, Korea.
Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Korea.
Sci Rep. 2020 Feb 27;10(1):3652. doi: 10.1038/s41598-020-60707-x.
In this study we assessed the clinical significance of an epithelial-mesenchymal transition (EMT) gene signature and explored its association with the tumor microenvironment related to immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC). Genes were selected when mRNA levels were positively or negatively correlated with at least one well-known EMT marker. We developed an EMT gene signature consisting of 82 genes. The patients were classified into epithelial or mesenchymal subgroups according to EMT signature. The clinical significance of the EMT signature was validated in three independent cohorts and its association with several immunotherapy-related signatures was investigated. The mesenchymal subgroup showed worse prognosis than the epithelial subgroup, and significantly elevated PD-1, PD-L1, and CTLA-4 levels, and increased interferon-gamma, cytolytic, T cell infiltration, overall immune infiltration, and immune signature scores. The relationship between PD-L1 expression and EMT status in HNSCC after treatment with TGF-β was validated in vitro. In conclusion, the EMT gene signature was associated with prognosis in HNSCC. Additionally, our results suggest that EMT is related to immune activity of the tumor microenvironment with elevated immune checkpoint molecules.
在这项研究中，我们评估了上皮-间充质转化 (EMT) 基因特征的临床意义，并探讨了其与头颈部鳞状细胞癌 (HNSCC) 中与免疫治疗相关的肿瘤微环境的关联。当 mRNA 水平与至少一个已知的 EMT 标志物呈正相关或负相关时，我们选择了基因。我们开发了一个由 82 个基因组成的 EMT 基因特征。根据 EMT 特征将患者分为上皮或间质亚组。在三个独立的队列中验证了 EMT 特征的临床意义，并研究了其与几种免疫治疗相关特征的关联。间质亚组的预后比上皮亚组差，且 PD-1、PD-L1 和 CTLA-4 水平显著升高，干扰素-γ、细胞毒性、T 细胞浸润、整体免疫浸润和免疫特征评分增加。在体外验证了 TGF-β 治疗后 HNSCC 中 PD-L1 表达与 EMT 状态之间的关系。总之，EMT 基因特征与 HNSCC 的预后相关。此外，我们的结果表明 EMT 与肿瘤微环境的免疫活性有关，免疫检查点分子水平升高。
