Colorectal cancer is a heterogenous group of neoplasms showing a variety of clinical and pathological features depending on their anatomical location. Sphingolipids are involved in the formation and progression of cancers, and their changes are an important part of the abnormalities observed during carcinogenesis. Because the course of rectal and colonic cancer differs, the aim of the study was to assess whether the sphingolipid profile is also different in tumors of these two regions. Using a combination of ultra-high-performance liquid chromatography combined with triple quadrupole mass spectrometry, differences in the amounts of cellular sphingolipids were found in colorectal cancer. Sphingosine content was higher in rectal cancer than in adjacent healthy tissue, while the content of two ceramides (C18:0-Cer and C20:0-Cer) was lower. In colon cancer, a higher content of sphingosine, sphinganine, sphingosine-1-phosphate, and two ceramides (C14:0-Cer and C24:0-Cer) was found compared to healthy tissue, but there was no decrease in the amount of any of the assessed sphingolipids. In rectal cancer, the content of sphinganine and three ceramides (C16:0-Cer, C22:0-Cer, C24:0-Cer), as well as the entire pool of ceramides, was significantly lower compared to colon cancer. The S1P/Cer ratio in rectal cancer (S1P/C18:1-Cer, S1P/C20:0-Cer, S1P/C22:0-Cer, S1P/C24:1-Cer) and in colon cancer (S1P/C18:0-Cer, S1P/C18:1-Cer, S1P/C20:0-Cer) was higher than in adjacent healthy tissue and did not differ between the two sites (rectal cancer vs. colonic cancer). It seems that the development of colorectal cancer is accompanied by complex changes in the metabolism of sphingolipids, causing not only qualitative shifts in the ceramide pool of cancer tissue but also quantitative disturbances, depending on the location of the primary tumor.

Reliable indicators of cancer advancement have actively been sought recently. The detection of colorectal cancer progression markers is essential in improving diagnostic and therapeutic protocols. The aim of the study was to investigate the profile of E-cadherin expression in colorectal cancer tissue depending on the TNM staging and its correlation with several clinical and histopathological features. The study included 55 colorectal cancer patients admitted to the surgical ward for elective surgery. Tissue samples were obtained from resected specimens. Different distributions of E-cadherin expression within tumors were observed; the highest percentage of positive E-cadherin expression was found in the invasive front and in the tumor center. Additionally, the different cellular distribution of E-cadherin expression was noticed; weak membranous E-cadherin expression was the highest in the invasive front and in the budding sites, but a strong membranous pattern was most frequent in the tumor center. Various distributions of E-cadherin expression depending on cancer progression were also found; E-cadherin expression in node-positive patients was lower in the tumor center and in the tumor invasive front, whereas, in patients with distant metastases, the expression of E-Cadherin was lower in the budding sites. In patients with higher TNM stages, E-cadherin expression was lower within the tumor (in the budding sites, tumor center, and invasive front). In tumors with lymphoid follicles, E-cadherin expression was higher in all localizations within the primary tumor. E-cadherin expression in the tumor center was also lower in tumors with some higher tumor budding parameters (areas of poorly differentiated components and poorly differentiated clusters). E-cadherin expression was found to be lower at the tumor center in younger individuals, at the budding sites in men, and at the surrounding lymph nodes in rectal tumors. Low E-cadherin expression appears to be a reliable indicator of higher cancer staging and progression. When assessing the advancement of cancer, apart from the TNM classification, it is beneficial to also consider the expression of E-cadherin. High tumor budding, the poverty of lymphoid follicles, and low E-cadherin expression analyzed simultaneously may contribute to a reliable assessment of colorectal cancer staging. These three histopathological features complement each other, and their investigation, together with conventional tumor staging and grading, may be very helpful in predicting the prognosis of colorectal cancer patients and qualifying them for the best treatment. The role of E-cadherin in the diagnosis and treatment of colorectal cancer, as a part of a personalized medicine strategy, still requires comprehensive, prospective clinical evaluations to precisely target the optimal therapies for the right patients at the right time.

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.