Table 6_Integrated cytomembrane proteomics identifies EpCAM/MGST1 as therapeutic targets in metastatic laryngeal carcinoma.xlsx

BackgroundLymph 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.
MethodsThis 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 in silico screening algorithm for cytomembrane proteome.
ResultsThe in silico 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 in vitro proliferation, invasion, and migration. Furthermore, their knockdown hindered the Wnt/β-catenin and PI3K signaling pathways.
ConclusionIntegrated 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.

背景：淋巴结转移（lymph node metastasis）在癌症复发与患者生存中发挥关键作用，但喉癌（laryngeal carcinoma）的潜在分子机制与生物标志物仍未得到充分阐明。细胞膜蛋白（cytomembrane proteins）因易于靶向而成为极具潜力的治疗靶点，然而筛选可用于精准治疗的可行候选靶点仍颇具挑战。
方法：本研究旨在通过细胞膜蛋白质组（cytomembrane proteome）分析，筛选伴淋巴结转移的喉鳞状细胞癌（laryngeal squamous cell carcinoma, LSCC）的潜在治疗靶点。我们从TCGA（111例患者）与CPTAC（47例患者）数据库中选取158例LSCC病例，开展了全面的多组学分析。本研究探究了淋巴结转移与蛋白质组层面分子特征之间的关联，并通过细胞膜蛋白质组的计算机模拟（in silico）筛选算法，鉴定并优先排序了潜在的免疫治疗靶点。
结果：针对细胞膜蛋白质组的计算机模拟筛选算法将EpCAM与MGST1鉴定为潜在靶点。我们证实，EpCAM与MGST1在LSCC组织中高表达，尤其在伴淋巴结转移的病例中表达更为显著。功能实验中，小干扰RNA（small interfering RNA, siRNA）敲低实验证实了二者在驱动肿瘤细胞体外增殖、侵袭与迁移过程中的关键作用。此外，敲低这两个基因会抑制Wnt/β-连环蛋白（Wnt/β-catenin）与PI3K信号通路。
结论：对转移性LSCC开展整合细胞膜蛋白质组学研究，揭示了EpCAM/MGST1可作为可靶向的免疫治疗靶点；敲低这两个靶点可减弱肿瘤细胞的增殖、侵袭能力，并阻断Wnt/β-连环蛋白-PI3K信号通路串扰，为喉癌治疗提供了全新的途径。