Claudin18.2 defines a prognostically distinct subgroup of intrahepatic cholangiocarcinoma via CD8+ T-cell exclusion

作者：Chengui Yu, Yuren Pan, Fuli Li, Zhenyun Guo, Da Xu, Ying Zhu, Baobing Yin · 发表于：Frontiers in Oncology · 年份：2025 · DOI：10.3389/fonc.2025.1636367 · 被引用次数：2 · 研究领域：Pancreatic and Hepatic Oncology Research、Barrier Structure and Function Studies、Cholangiocarcinoma and Gallbladder Cancer Studies

Background and purpose Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with limited therapeutic options. Claudin18.2 (CLDN18.2), a tight junction protein aberrantly expressed in gastrointestinal cancers, has not been systematically evaluated in ICC. This study investigates CLDN18.2’s expression, clinical relevance, and interplay with the tumor immune microenvironment (TIME) in ICC. Method CLDN18.2 expression was analyzed in 83 ICC and 47 matched non-tumor tissues on tissue microarray sections using immunohistochemistry (IHC). Bioinformatics validation utilized ArrayExpress (E-MTAB-6389) and GEO (GSE119336, GSE107943, GSE89749, GSE32225) datasets. Clinicopathological correlations, survival analysis, and CD8 + tumor-infiltrating lymphocytes (TILs) quantification were performed. Results CLDN18.2 was exclusively expressed in 24.1% (20/83) of ICC tissues, absent in non-tumor tissues. Positive CLDN18.2 expression correlated with elevated serum CA19-9 ( P = 0.026), smaller tumor size ( P = 0.03), unifocality ( P = 0.03), and higher recurrence ( P = 0.018). Multivariable analysis identified CLDN18.2 as an independent prognostic factor for reduced overall survival (OS: HR = 2.555, 95% CI = 1.250–5.223, P = 0.01) and disease-free survival (DFS: HR = 2.229, 95% CI = 1.125–4.415, P = 0.022). Single-sample gene set enrichment analysis (ssGSEA) analysis revealed an inverse correlation between CLDN18 expression and CD8 + T cells ( P = 0.012), while IHC showed a trend towar...