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CLDN-2 Expression Aligns with Invasion-Associated Epithelial Remodeling in Colorectal Cancer
by
, , , and
Adam R. Markowski
1,*,
Anna J. Sadowska
2,
Konstancja Mantiuk
3,
Wiktoria Romańczyk
4,
Anna Pryczynicz
4 and
Katarzyna Guzińska-Ustymowicz
4 1
Department of Hypertensiology, Gastroenterology and Internal Medicine, Medical University of Bialystok, 14 Żurawia Street, 15-540 Bialystok, Poland
2
Department of Cardiology and Internal Medicine, Provincial Welded Hospital in Bialystok, 26 Maria Skłodowska-Curie Street, 15-950 Bialystok, Poland
3
Medical University of Warsaw, 61 Żwirki i Wigury Street, 02-091 Warsaw, Poland
4
Department of General Pathomorphology, Medical University of Bialystok, 13 Waszyngtona Street, 15-269 Bialystok, Poland
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(11), 1772; https://doi.org/10.3390/cancers18111772
Submission received: 12 May 2026
/
Revised: 24 May 2026
/
Accepted: 26 May 2026
/
Published: 28 May 2026
(This article belongs to the Special Issue Cancer Metastasis in 2025–2026)
Simple Summary
Colorectal cancer progression involves changes in how tumor cells are organized and interact with each other. However, the structural features that accompany early spread are not fully understood. In this study, we examined the expression of a protein called Claudin-2 in tumor samples and analyzed its relationship with features of early dissemination. We found that higher Claudin-2 expression is associated with patterns linked to early spread, including tumor budding and spatial changes in cell adhesion across different tumor regions. These patterns showed limited alignment with measures of immune-cell infiltration, suggesting that epithelial organization and immune contexture may represent partially independent aspects of tumor biology. Overall, our findings suggest that Claudin-2 is associated with a specific structural organization of the tumor that may accompany early dissemination. These observations may help guide further biological and translational studies.
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.
