Analysis of Transcriptional Factors and Regulation Networks in Laryngeal Squamous Cell Carcinoma Patients with Lymph Node Metastasis

The present study was to identify and quantitate differentially expressed proteins in laryngeal squamous cell carcinoma (LSCC) tissues with or without lymph node metastasis and to explore transcriptional factors and regulation networks associated with the process. Tissue specimens were taken from 20 patients with LSCC, including 10 cases of LSCC without metastasis LSCC (N0) and 10 cases of LSCC with metastasis LSCC (Nx). Among the 643 unique proteins identified by using iTRAQ labeling and quantitative proteomic technology, 389 proteins showed an abundance change in LSCC (Nx) as compared to LSCC (N0). Cytoskeleton remodeling, cell adhesion, and immune response activation were found to be the main processes in LSCC metastasis. The construction of transcription regulation networks identified key transcription regulators for lymph node metastasis of LSCC, including Sp1, c-myc, and p53, which may affect LSCC metastasis through the epithelial–mesenchymal transition. Furthermore, our results suggest that ubiquitination may be a critical factor in the networks. The present study provides insights into transcriptional factors and regulation networks involved in LSCC metastasis, which may lead to new strategies for treatment of LSCC metastasis.

本研究旨在鉴定并定量分析伴或不伴淋巴结转移的喉鳞状细胞癌（laryngeal squamous cell carcinoma, LSCC）组织中的差异表达蛋白，并探索与该转移过程相关的转录因子及调控网络。本研究纳入20例喉鳞状细胞癌患者的组织标本，其中10例为无淋巴结转移的喉鳞状细胞癌（N0期），另外10例为伴淋巴结转移的喉鳞状细胞癌（Nx期）。通过同位素标记相对和绝对定量（isobaric tags for relative and absolute quantitation, iTRAQ）标记技术与定量蛋白质组学方法，本研究共鉴定出643种独特蛋白；与N0期喉鳞状细胞癌组织相比，Nx期组织中有389种蛋白的表达丰度发生显著变化。研究发现，细胞骨架重塑、细胞黏附以及免疫应答激活是喉鳞状细胞癌淋巴结转移的主要生物学过程。通过构建转录调控网络，本研究鉴定出喉鳞状细胞癌淋巴结转移的关键转录调控因子，包括Sp1、c-myc及p53，这些因子可能通过上皮间质转化（epithelial-mesenchymal transition, EMT）影响喉鳞状细胞癌的转移进程。此外，本研究结果显示泛素化可能是该调控网络中的关键影响因素。本研究为阐明喉鳞状细胞癌淋巴结转移相关的转录因子及调控网络提供了新的视角，有望为喉鳞状细胞癌淋巴结转移的临床治疗提供全新策略。