Zhuang Suling, Wu Xiaobo, Lin Xiaohuang, Li Zhihan, Gan Di, Wang Shixin, Lin Xue, Lin Gongbiao, Gao Miao
Department of Otorhinolaryngology Head and Neck Surgery, Fujian Institute of Otorhinolaryngology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Department of Otorhinolaryngology Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Front Genet. 2025 Jul 24;16:1615570. doi: 10.3389/fgene.2025.1615570. eCollection 2025.
Lymph node metastasis plays a crucial role in cancer recurrence and survival, however, the underlying molecular mechanism and biomarkers in laryngeal carcinoma remain poorly characterized. While cytomembrane proteins represent attractive therapeutic targets due to their accessibility, the identification of tractable candidates for precision therapy remains challenging.
This study aimed to identify potential therapeutic targets for laryngeal squamous cell carcinoma (LSCC) with lymph node metastasis through cytomembrane proteome profiling. We conducted a comprehensive multi-omics analysis in 158 LSCC cases from TCGA (111 patients) and CPTAC (47 patients) database. The correlations between lymph node metastasis and molecular features at proteome levels were investigated. Potential immunotherapy targets were identified and prioritized using an screening algorithm for cytomembrane proteome.
The screening algorithm for cytomembrane proteome led to the recognition of EpCAM and MGST1 as potential targets. We demonstrated that EpCAM and MGST1 were abundantly expressed in LSCC, particularly in cases with lymph node metastasis. Functional siRNA knockdown confirmed their critical roles in driving proliferation, invasion, and migration. Furthermore, their knockdown hindered the Wnt/β-catenin and PI3K signaling pathways.
Integrated cytomembrane proteomics in metastatic LSCC unveils EpCAM/MGST1 as actionable immunotherapeutic targets, with silencing attenuating oncogenic proliferation, invasion, and Wnt/β-catenin-PI3K crosstalk, offering novel therapeutic avenues.
淋巴结转移在癌症复发和生存中起着关键作用，然而，喉癌潜在的分子机制和生物标志物仍未得到充分表征。由于细胞膜蛋白易于接近，它们是有吸引力的治疗靶点，但确定用于精准治疗的易处理候选靶点仍然具有挑战性。
本研究旨在通过细胞膜蛋白质组分析确定伴有淋巴结转移的喉鳞状细胞癌（LSCC）的潜在治疗靶点。我们对来自TCGA（111例患者）和CPTAC（47例患者）数据库的158例LSCC病例进行了全面的多组学分析。研究了蛋白质组水平上淋巴结转移与分子特征之间的相关性。使用细胞膜蛋白质组筛选算法识别并优先排序潜在的免疫治疗靶点。
细胞膜蛋白质组筛选算法识别出EpCAM和MGST1为潜在靶点。我们证明EpCAM和MGST1在LSCC中大量表达，尤其是在伴有淋巴结转移的病例中。功能性siRNA敲低证实了它们在驱动细胞增殖、侵袭和迁移中的关键作用。此外，它们的敲低阻碍了Wnt/β-连环蛋白和PI3K信号通路。
转移性LSCC中的综合细胞膜蛋白质组学揭示EpCAM/MGST1为可操作的免疫治疗靶点，其沉默可减弱致癌增殖、侵袭以及Wnt/β-连环蛋白-PI3K串扰，提供了新的治疗途径。
