Comprehensive analysis reveals CLDN9 is a new biomarker in human cancers and immunotherapeutic target for glioblastoma multiforme.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.