Wang Zhuangzhi, Sun Changning, Wang Pengfei, Lin Shouyang, Wu Xiao, Gu Yuchao
Qingdao Center of Technology Innovation for Shark Antibody Development, College of Biological Engineering, Qingdao University of Science and Technology, Qingdao, China.
School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.
Front Immunol. 2025 May 30;16:1578627. doi: 10.3389/fimmu.2025.1578627. eCollection 2025.
Transmembrane emp24 domain-containing protein 2 (TMED2) is involved in the sorting and transport of proteins between the Golgi apparatus and the endoplasmic reticulum. Recent research has identified a close association between TMED2 and tumorigenesis, yet its regulatory role and underlying mechanisms in pan-cancer signaling pathways remain unexplored.
We conducted a comprehensive pan-cancer analysis of TMED2 using multiple public databases. These analyses included assessments of prognostic significance, gene mutations, pathway enrichment, single-cell sequencing analysis, immune characteristics, co-expressed gene PPI network analysis, as well as the therapeutic response of TMED2 in immunotherapy and small molecule sensitivity. Finally, we examined the role that TMED2 plays at the cellular level.
Our results show that the mRNA levels of TMED2 differ significantly between cancerous and normal tissues and are closely associated with cancer prognosis. Specifically, in CESC, MESO, LGG, and UVM, overexpression of TMED2 correlates with patient prognosis and various clinical pathological features. TMED2 is significantly associated with immune infiltration (including endothelial cells, neutrophils, dendritic cells, and eosinophils), immune checkpoints (CD274, HAVCR2, PDCD1LG2, and SIGLEC15), and signaling pathways (cell cycle and PI3K/Akt). Single-cell sequencing reveals that TMED2 is predominantly expressed in tumor cells of cervical cancer, glioma, and mesothelioma. Enrichment analysis shows that genes co-expressed with TMED2 are primarily involved in processes like endoplasmic reticulum stress and the ERAD pathway. Furthermore, cellular studies indicated that TMED2 expression promotes the growth, migration and invasion of glioma cells.
Our integrated analysis suggests that targeting TMED2, along with its associated genes and signaling pathways, could represent a new strategy for cancer immune treatment.
跨膜含emp24结构域蛋白2（TMED2）参与蛋白质在高尔基体和内质网之间的分选与运输。最近的研究已确定TMED2与肿瘤发生密切相关，但其在泛癌信号通路中的调控作用及潜在机制仍未得到探索。
我们使用多个公共数据库对TMED2进行了全面的泛癌分析。这些分析包括评估预后意义、基因突变、通路富集、单细胞测序分析、免疫特征、共表达基因PPI网络分析，以及TMED2在免疫治疗和小分子敏感性方面的治疗反应。最后，我们研究了TMED2在细胞水平上所起的作用。
我们的结果表明，TMED2的mRNA水平在癌组织和正常组织之间存在显著差异，并且与癌症预后密切相关。具体而言，在子宫颈癌、间皮瘤、低级别胶质瘤和葡萄膜黑色素瘤中，TMED2的过表达与患者预后及各种临床病理特征相关。TMED2与免疫浸润（包括内皮细胞、中性粒细胞、树突状细胞和嗜酸性粒细胞）、免疫检查点（CD274、HAVCR2、PDCD1LG2和SIGLEC15）以及信号通路（细胞周期和PI3K/Akt）显著相关。单细胞测序显示，TMED2主要在宫颈癌、胶质瘤和间皮瘤的肿瘤细胞中表达。富集分析表明，与TMED2共表达的基因主要参与内质网应激和ERAD途径等过程。此外，细胞研究表明，TMED2的表达促进了胶质瘤细胞的生长、迁移和侵袭。
我们的综合分析表明，靶向TMED2及其相关基因和信号通路可能代表一种新的癌症免疫治疗策略。
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