Zhu Yuanyuan, Li Ning, Peng Fang
Department of Blood Transfusion, Xiangya Hospital, Clinical Transfusion Research Center, Central South University, Changsha, Hunan Province, 410008, China.
Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China.
Cancer Cell Int. 2025 Jun 18;25(1):216. doi: 10.1186/s12935-025-03852-5.
Claudin-9 (CLDN9) plays a pivotal role in forming tight junctions and adhesion among epithelial cells. Despite its importance, comprehensive investigations into the role of CLDN9 in various cancers have been lacking.
We conducted a thorough analysis of CLDN9 across multiple cancer types using omics data and assessed its expression in glioblastoma multiforme (GBM) tissues via immunohistochemistry. To explore the impact of CLDN9 on tumor growth, we employed a subcutaneous GBM animal model. Furthermore, we utilized transwell experiments to evaluate cell migration and invasion capabilities.
Our findings reveal significant variations in CLDN9 expression across different cancers and among molecular and immune subtypes. CLDN9 demonstrates impressive predictive accuracy for certain cancer types and shows strong associations with cancer prognosis. IHC confirmed downregulated CLDN9 expression in GBM tissues, and its expression correlated with clinicopathological parameters of GBM patients. Specifically, in GBM, CLDN9 expression negatively correlated with activated CD8 T cells, activated dendritic cells, plasmacytoid dendritic cells, and type 1 helper cells. Moreover, we observed associations between CLDN9 expression and immunostimulators, immunoinhibitors, and major histocompatibility complex molecules. In vitro experiments indicated that CLDN9 overexpression reduced the migratory and invasive capabilities of GBM cells.
Overall, our study provides valuable insights into the role of CLDN9 in various tumors and lays a foundation for more precise and individualized immunotherapy approaches for GBM in the future.
Claudin-9（CLDN9）在上皮细胞间紧密连接和黏附的形成中起关键作用。尽管其很重要，但对CLDN9在各种癌症中作用的全面研究仍很缺乏。
我们使用组学数据对多种癌症类型中的CLDN9进行了全面分析，并通过免疫组织化学评估了其在多形性胶质母细胞瘤（GBM）组织中的表达。为了探究CLDN9对肿瘤生长的影响，我们采用了皮下GBM动物模型。此外，我们利用Transwell实验评估细胞迁移和侵袭能力。
我们的研究结果揭示了CLDN9在不同癌症以及分子和免疫亚型之间的表达存在显著差异。CLDN9对某些癌症类型具有令人印象深刻的预测准确性，并与癌症预后密切相关。免疫组织化学证实GBM组织中CLDN9表达下调，其表达与GBM患者的临床病理参数相关。具体而言，在GBM中，CLDN9表达与活化的CD8 T细胞、活化的树突状细胞、浆细胞样树突状细胞和1型辅助性T细胞呈负相关。此外，我们观察到CLDN9表达与免疫刺激剂、免疫抑制剂和主要组织相容性复合体分子之间存在关联。体外实验表明，CLDN9过表达降低了GBM细胞的迁移和侵袭能力。
总体而言，我们的研究为CLDN9在各种肿瘤中的作用提供了有价值的见解，并为未来GBM更精确和个性化的免疫治疗方法奠定了基础。
