Chen Li-Guo, Fang Yu-Han, Wang Kui-Ming, Zhang Wei, Chen Gang
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
College of Life Sciences, Wuhan University, Wuhan 430072, China.
Biomolecules. 2025 Feb 22;15(3):323. doi: 10.3390/biom15030323.
The ESCRT (endosomal sorting complex required for transport) machinery is essential for various cellular processes, yet its role in head and neck squamous cell carcinoma (HNSCC) is poorly understood. We utilized The Cancer Genome Atlas (TCGA) datasets to analyze the expression of ESCRT genes. Bulk RNA-sequencing data and HNSCC tissue microarrays (TMAs) were used to evaluate VPS25 expression and its clinical significance. Single-cell RNA sequencing of tumor tissues and knockdown experiments in CAL27 cells were used to investigate its biological functions. Immunohistochemistry, spatial transcriptomics, and immunotherapy datasets highlighted the involvement of VPS25 in immune suppression and its potential as a predictive biomarker. The results demonstrated significant VPS25 overexpression in HNSCC tissues, which correlated with poor clinical outcomes. It promoted tumor cell proliferation and migration while reducing immune cell infiltration in the tumor microenvironment (TME). Additionally, by upregulating PVR expression in tumor cells, VPS25 activated the immunosuppressive PVR-TIGIT signaling axis, thereby facilitating immune evasion. Furthermore, emerged as a potential biomarker for predicting immunotherapy response. These findings highlight VPS25 as a pivotal regulator of tumor progression and immune evasion in HNSCC and a promising target for therapeutic strategies.
内体分选转运所需复合物（ESCRT）机制对多种细胞过程至关重要，但其在头颈部鳞状细胞癌（HNSCC）中的作用仍知之甚少。我们利用癌症基因组图谱（TCGA）数据集来分析ESCRT基因的表达。采用批量RNA测序数据和HNSCC组织微阵列（TMA）来评估VPS25的表达及其临床意义。利用肿瘤组织的单细胞RNA测序和CAL27细胞中的敲低实验来研究其生物学功能。免疫组织化学、空间转录组学和免疫治疗数据集突出了VPS25在免疫抑制中的作用及其作为预测性生物标志物的潜力。结果表明，HNSCC组织中VPS25显著过表达，这与不良临床结果相关。它促进肿瘤细胞增殖和迁移，同时减少肿瘤微环境（TME）中的免疫细胞浸润。此外，VPS25通过上调肿瘤细胞中PVR的表达，激活免疫抑制性PVR-TIGIT信号轴，从而促进免疫逃逸。此外，VPS25成为预测免疫治疗反应的潜在生物标志物。这些发现突出了VPS25作为HNSCC肿瘤进展和免疫逃逸的关键调节因子以及治疗策略的有前景靶点的作用。
