Work

CLDN-2 Expression Aligns with Invasion-Associated Epithelial Remodeling in Colorectal Cancer

Year: 2026

Type: article

Abstract: BACKGROUND: Remodeling of epithelial junctional architecture contributes to colorectal cancer (CRC) progression; however, the spatial organization linking tight-junction components to early dissemination remains incompletely characterized. Claudin-2 (CLDN-2) is frequently upregulated in CRC, yet whether it is associated with compartment-specific epithelial remodeling has not been systematically examined. METHODS: In a retrospective single-center cohort of 54 surgically resected CRCs, we integrated clinicopathological variables, quantitative tumor budding counts, compartment-specific membranous E-cadherin expression, lymphovascular invasion, lymphoid follicles, and immune-cell densities. Analyses focused on spatial structural relationships within the tumor. RESULTS: Higher CLDN-2 expression was enriched among node-positive tumors and advanced TNM stages. CLDN-2-higher tumors exhibited increased tumor budding and spatially selective adhesion remodeling, characterized by reduced membranous E-cadherin at the invasive front and budding sites, with more preserved membranous epithelial organization within metastatic lymph-node deposits. Descriptive co-occurrence and correlation analyses demonstrated concordant spatial relationships among CLDN-2 expression, tumor budding, nodal involvement, lymphovascular invasion, and compartment-specific E-cadherin patterns. In contrast, immune-related parameters showed weaker differentiation across CLDN-2 strata. CONCLUSIONS: CLDN-2 expression is associated with spatial epithelial remodeling in colorectal cancer, characterized by compartment-specific adhesion changes and increased microinvasive activity. The findings support a model in which CLDN-2 expression aligns with an invasion-associated epithelial configuration linked to tumor budding and nodal dissemination. These observations warrant validation in independent cohorts with outcome data.

Source: Cancers

DOI: 10.3390/cancers18111772

Authors: Adam R. Markowski, Anna J. Sadowska, Konstancja Mantiuk, Wiktoria Romańczyk, Anna Pryczynicz, Katarzyna Guzińska-Ustymowicz

Institutions: Medical University of Białystok, Medical University of Warsaw

Language: English

Topic: Cancer Cells and Metastasis

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499