Zhu Jing, Yu Chun, Xu Xin, Zou Chu, Li Jiaqi, Wang Rui, Li Xinchao, Sun Aijun, Wang Shiyan, Jiang Chao
Department of Oncology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
General Surgery Department, Lianshui People's Hospital Affiliated to Kangda College of Nanjing Medical University, Huai'an, Jiangsu, China.
Front Immunol. 2025 Aug 6;16:1619733. doi: 10.3389/fimmu.2025.1619733. eCollection 2025.
The protein belongs to the family and is primarily localized to early endosomes. It regulates the endocytic pathway through its GTPase activity, thereby affecting various aspects such as cell signaling and metabolic regulation. Dysfunction of is closely associated with the progression and deterioration of multiple types of tumors. Although studies have revealed the functional mechanisms of in specific tumor types, its role in pan-cancer and the underlying molecular mechanisms still lack in-depth analysis.
A comparative analysis of gene expression was conducted using transcriptomic datasets from Cancer Genome Map (TCGA) and Genotype-Tissue Expression (GTEx), followed by tissue distribution profiling via Human Protein Atlas (HPA) and GeneMANIA to map its expression across human tissues. The TISCH database identified primary cell types expressing within the tumor microenvironment, while univariate Cox regression modeling evaluated its prognostic significance in cancer outcomes. Integrative genomic analyses using cBioPortal and Gene Set Cancer Analysis (GSCA) further characterized 's genomic alterations and cancer-specific profiles. Gene_DE module 2.0 (TIMER 2.0) deciphered associations between expression and tumor-infiltrating immune cell subsets. To elucidate functional mechanisms, Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) identified biological pathways co-regulated with , and in silico approaches combining CellMiner with molecular docking predicted interactions between and anticancer drugs. wound healing assays were performed to validate 's role in modulating cellular migration dynamics, complementing bioinformatics findings with experimental evidence.
protein expression varied significantly across tumors, with different prognostic values. In most malignancies, expression correlated positively with Copy Number Variation (CNV) and methylation. It also correlated significantly with immunotherapy biomarkers and responses. ESTIMATE and immune infiltration analyses highlighted 's link to immunosuppression, emphasizing its role in immune regulation. Molecular docking and experimental validation showed that downregulating inhibited cell proliferation and reduced cancer cell migration.
Our study revealed the key role of in tumor biomarkers. inhibits ectopic metastasis of tumor cells mainly by regulating the process of cell adhesion and migration. This discovery is of great significance for developing new anticancer inhibitors.
该蛋白属于某家族，主要定位于早期内体。它通过其GTPase活性调节内吞途径，从而影响细胞信号传导和代谢调节等多个方面。该蛋白功能异常与多种肿瘤的进展和恶化密切相关。尽管研究已经揭示了该蛋白在特定肿瘤类型中的功能机制，但其在泛癌中的作用及潜在分子机制仍缺乏深入分析。
使用来自癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）的转录组数据集对该基因表达进行比较分析，随后通过人类蛋白质图谱（HPA）和基因共表达网络分析工具（GeneMANIA）进行组织分布分析，以绘制其在人体组织中的表达图谱。TISCH数据库确定了肿瘤微环境中表达该蛋白的主要细胞类型，而单变量Cox回归模型评估了其在癌症预后中的预后意义。使用cBioPortal和基因集癌症分析（GSCA）进行的综合基因组分析进一步表征了该蛋白的基因组改变和癌症特异性特征。基因差异表达模块2.0（TIMER 2.0）解读了该蛋白表达与肿瘤浸润免疫细胞亚群之间的关联。为了阐明功能机制，基因集富集分析（GSEA）和基因集变异分析（GSVA）确定了与该蛋白共同调控的生物途径，并且将CellMiner与分子对接相结合的计算机模拟方法预测了该蛋白与抗癌药物之间的相互作用。进行了伤口愈合试验以验证该蛋白在调节细胞迁移动力学中的作用，用实验证据补充生物信息学研究结果。
该蛋白在不同肿瘤中的表达差异显著，具有不同的预后价值。在大多数恶性肿瘤中，该蛋白表达与拷贝数变异（CNV）和甲基化呈正相关。它还与免疫治疗生物标志物和反应显著相关。ESTIMATE和免疫浸润分析突出了该蛋白与免疫抑制的联系，强调了其在免疫调节中的作用。分子对接和实验验证表明，下调该蛋白可抑制细胞增殖并减少癌细胞迁移。
我们的研究揭示了该蛋白在肿瘤生物标志物中的关键作用。该蛋白主要通过调节细胞黏附和迁移过程来抑制肿瘤细胞的异位转移。这一发现对于开发新的抗癌抑制剂具有重要意义。
