Dariusz Waniczek

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and its molecular pathogenesis is not fully understood. This exploratory study investigated the expression of three selected microRNAs in colorectal cancer and their associations with previously characterized ADAM transcripts. RT-qPCR was used to assess miR-125b-5p, miR-338-3p, and miR-30c-5p in paired tumor and histologically tumor-free surgical margin tissues from 67 patients. Previously obtained ADAM10, ADAM12, ADAM17, and ADAM28 transcript data from the same cohort were included in correlation analyses. The Wilcoxon signed-rank test and Spearman’s rank correlation were applied, with Benjamini–Hochberg adjustment for multiple testing. MiR-125b-5p expression was lower in tumors than in matched margins (median 0.46 versus 1.33; adjusted p = 0.035). No significant paired differences were identified for miR-338-3p or miR-30c-5p. Margin miR-125b-5p expression was associated with neoadjuvant-treatment history (adjusted p = 0.033), although the treated subgroup was small. No miRNA-ADAM transcript correlations remained significant after adjustment. Positive correlations among some miRNA pairs were observed within tumor and margin tissues. The reduced level of relative miR-125b-5p expression in colorectal cancers is an observational finding consistent with the tumor-suppressor functions described in the literature, but it does not constitute proof of those functions. Inter-miRNA correlations do not demonstrate shared regulatory mechanisms, and the absence of miRNA-ADAM transcript associations does not exclude post-transcriptional regulation.

The role of adamalysins (ADAMs) has been widely described in many processes related to carcinogenesis, angiogenesis, inflammation, metastasis, and metabolic disorders. Despite numerous studies, their role in colorectal cancer (CRC) remains unclear. The aim of this study was to evaluate the expression of selected ADAM genes in colorectal cancer tissue and corresponding surgical margins. In addition, for a subgroup of patients, the expression of selected proteins from the ADAM family was assessed. The final study group consisted of 67 patients who underwent elective surgery for colorectal cancer. The relative expression of the ADAM10, 12, 17, and 28 genes was expressed as relative quantification (RQ) and determined by real-time quantitative PCR (RT-qPCR) in tumor tissue and surgical margins. In addition, for a subgroup of 45 patients, the expression of ADAM10, 12, and 17 proteins was assessed by ELISA. Associations between ADAM expression and clinicopathological parameters were analyzed statistically. ADAM12 gene expression was significantly higher in tumor than in margin tissue (median RQ: 0.995 vs. 0.251; p = 0.003), whereas ADAM28 RQ was significantly higher in the margin (median RQ: 0.400 vs. 0.204; p = 0.021). No significant differences were observed in the expression of the ADAM10, ADAM12, ADAM17, or ADAM28 genes based on tumor stage, sex, substance use, BMI, or age, except for nominally higher ADAM12 gene expression in patients over 65 years of age (p = 0.033). Among patients under 65 years of age with cardiovascular disease (CVD), ADAM28 RQ in tumor tissue was significantly higher than in those without CVD (p < 0.05). In obese patients with CVD, a markedly increased expression of ADAM28 in tumor tissue was observed, regardless of age (1.469 vs. 0.132; p < 0.005). Significant positive correlations were observed between the ADAM10 and ADAM17 RQ, and between the ADAM10 and ADAM28 RQ, in both tumor and marginal tissues (all adjusted p < 0.01). No significant correlations were found between gene expression and corresponding protein levels for ADAM10, ADAM12, or ADAM17. ADAM10, 12, 17, and 28 are poor biomarkers for colorectal cancer, but their significance may increase in patients with comorbid metabolic disorders. The lack of correlation between protein expression and gene expression suggests the contribution of post-transcriptional and post-translational regulatory mechanisms, which justifies further research.

Cartilage oligomeric matrix protein (COMP) influences extracellular matrix remodeling. We investigated its clinical, prognostic, and immunomodulatory significance in colorectal cancer (CRC). COMP was quantified via ELISA in 107 paired CRC and normal tissues. Expression was correlated with clinicopathological features, mutational profiles, microsatellite instability (MSI), tumor-infiltrating lymphocytes (TILs), immune checkpoints, and multiplex cytokine networks. For transcriptomic validation, the FieldEffectCrc dataset was used for Gene Set Enrichment Analysis (GSEA), and The Cancer Genome Atlas (TCGA) CRC cohort for survival analysis. COMP was significantly upregulated in CRC tissues (p < 0.001) and correlated with advanced T, N, and overall pathological stages (all p < 0.05, tau = 0.18, 0.21, and 0.23, respectively). High COMP expression was linked to restricted immune infiltration (reduced stromal TILs, p < 0.05, tau = −0.23), elevated levels in microsatellite stable (MSS) compared to MSI tumors (p < 0.01), and correlated positively with immune exhaustion markers (T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), galectin-9 (GAL9), sialic acid-binding Ig-like lectin 9 (SIGLEC9)). Transcriptomic data linked high COMP to worse disease-specific and progression-free survival, and enrichment in pro-tumorigenic pathways (epithelial-to-mesenchymal transition, angiogenesis, IL-6 signaling). COMP upregulation defines an immunosuppressive microenvironment in CRC, particularly in MSS tumors. It represents an important prognostic biomarker and potential therapeutic target for overcoming immunotherapy resistance.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. While established molecular biomarkers such as microsatellite instability (MSI), KRAS, and BRAF are routinely used in clinical practice, the prognostic relevance of tumor suppressor proteins p53 and PTEN remains incompletely defined, particularly when assessed using immunohistochemistry. Objective: The primary aim of this study was to evaluate the prognostic significance of p53 expression and PTEN deficiency in colorectal adenocarcinoma. Secondary aims included assessment of their association with clinicopathological characteristics. Methods: This retrospective cohort study included 103 consecutive patients who underwent surgical resection for colorectal adenocarcinoma. Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tumor samples was performed to assess aberrant p53 expression and PTEN deficiency. Associations with clinicopathological variables were evaluated, and overall survival was analyzed using Kaplan–Meier curves and Cox proportional hazards regression models. Results: Aberrant p53 expression and PTEN deficiency were both associated with shorter overall survival in univariate analyses. Patients with concurrent aberrant p53 expression and PTEN deficiency demonstrated the poorest survival outcomes. However, in multivariate Cox regression analysis, only nodal status and age remained independent predictors of overall survival, while p53 and PTEN did not retain independent prognostic significance after adjustment for clinicopathological variables. Conclusions: Aberrant p53 expression and PTEN deficiency are associated with reduced overall survival in colorectal cancer; however, their prognostic impact appears secondary to established clinicopathological factors. The combined presence of these alterations may identify a biologically aggressive subgroup of patients with particularly unfavorable outcomes, although this observation should be considered exploratory. Further validation in larger, independent cohorts is required.

Bicuspid aortic valve (BAV) is one of the most common congenital heart defects, introducing significant hemodynamic disturbances to the circulatory system. This narrative review analyzed articles published between 2012 and 2025 and indexed in PubMed. The aim was to synthesize key information on the etiopathogenesis of BAV, its potential complications and associated risks, as well as available pharmacological and surgical treatment strategies, with emphasis on indications and contraindications for specific surgical techniques. Analyses demonstrate that isolated BAV with typical valvular aortopathy is associated with a more favorable prognosis compared to valvular aortopathy syndromes. Valve phenotype shows important sex-related relationships in its presentation and progression. From a hemodynamic perspective, BAV alters blood flow angles, which may contribute to weakening of the aortic wall and secondary valve changes. BAV is also frequently associated with genetic disorders such as Marfan syndrome. The heterogeneity of aortopathies linked to BAV creates significant challenges for echocardiographers, cardiologists and cardiac surgeons, particularly in determining the optimal timing and strategy for surgical intervention.

Chronic inflammation is a recognized driver of colorectal cancer (CRC) development, particularly in patients with Crohn’s disease (CD). This study aimed to explore serum inflammatory cytokine profiles in patients with Crohn’s disease and colorectal cancer and to assess their associations with disease activity and tumor-related features. Seventy-eight participants were included: 24 with CD, 31 with CRC, and 23 healthy controls. Serum levels of 27 cytokines were measured using the Bio-Plex Pro Human Cytokine 27-plex Assay. Principal component analysis identified three cytokine clusters (factors). Factor 2, comprising IL-9, MIP-1β, and PDGF-β, was significantly elevated in CD patients compared to controls (p < 0.001), showed intermediate levels in CRC patients, and positively correlated with fecal calprotectin (R = 0.44; p = 0.04), indicating an association with local intestinal inflammation. In CRC patients, Factor 1, comprising key Th1/Th17 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-15, IL-17A, FGF-B, GM-CSF, IFN-γ, TNF-α, and VEGF), reflecting pro-inflammatory and cell-mediated immune signaling, correlated with lymph node metastasis (τ = 0.27; p = 0.03), while Factor 2 showed a trend toward a negative correlation with tumor histological grade (τ = −0.22; p = 0.09). Factor 3, encompassing regulatory and hematopoietic cytokines, did not differ significantly between groups (p = 0.21). These findings suggest that IL-9, MIP-1β, and PDGF-β reflect inflammatory activity and may be involved in inflammation-associated tumorigenic processes in the gut. Serum profiling of selected cytokines may provide biologically relevant information and support further investigation of inflammation-associated immune patterns in CD and CRC. Further studies are warranted to validate their clinical utility and to elucidate their mechanistic role in inflammation-driven colorectal carcinogenesis.

TIGIT and its ligand CD155 (PVR) are emerging immune checkpoints in colorectal cancer (CRC), but their associations with mutational subtypes and the tumor immune milieu remain unclear. We quantified TIGIT and CD155 proteins by ELISA in paired CRC tumors and matched surgical margins (n = 131) and evaluated associations with clinicopathological features, MSI status, and KRAS/NRAS/BRAF/PIK3CA/AKT1 mutations (n = 104). Both TIGIT and CD155 were significantly elevated in tumor tissue versus margins (p < 0.0001) and showed no association with TNM stage, clinical stage, grade, or tumor location. TIGIT levels were higher in MSI than MSS tumors and in BRAF-mutant compared to BRAF wild-type tumors, while CD155 expression showed no consistent MSI- or mutation-dependent differences. Cytokine profiling identified IFN-g as the only shared positive associate of TIGIT and CD155; CD155 additionally associated with TRAIL, IL-1Ra, M-CSF, and PDGF-bb. In external transcriptomic validation (TCGA-CRC), GSEA indicated enrichment of interferon/inflammatory programs in TIGIT-high tumors, while CD155-high tumors preferentially showed proliferation-related MYC/E2F/G2M signatures. Together, these findings support tumor-wide upregulation of the TIGIT/CD155 axis in CRC and suggest that TIGIT, more than CD155, tracks with MSI/BRAF-associated immune activation, providing a rationale for patient stratification in checkpoint-directed immunotherapy.

Crohn’s disease (CD) and colorectal cancer (CRC) are clinically distinct but pathogenetically related conditions in which significant abnormalities in autophagy are observed. The aim of the study was to evaluate the expression of three key autophagy-related genes, i.e., BECN1 (macroautophagy), PINK1 (mitophagy), and LAMP2 (chaperone-mediated autophagy) in tissue samples from patients with CD and CRC. The study material included samples from 48 patients with CD (n = 96 biopsy samples) and 87 patients with CRC (n = 87 tumors; n = 87 normal paired controls). Transcriptomic analyses were performed using Affymetrix HG-U133A microarrays. They were confirmed by RT-qPCR. The Kruskal–Wallis test with Dunn’s post hoc analysis (α = 0.05) and Spearman’s correlation coefficients were used for statistical evaluation. Expression of BECN1 and LAMP2 was significantly decreased in both CD and CRC compared to the controls (p = 0.009; p = 0.023, respectively). However, PINK1 showed significantly higher expression levels in CD compared to CRC and the controls (p < 0.001). The clinical stages of CRC (I–IV) did not significantly affect the expression of the analyzed genes. The study findings confirm the presence of common abnormalities in autophagy in CD and CRC, with decreased macroautophagy and chaperone-mediated autophagy, with the compensatory activation of mitophagy. BECN1, PINK1, and LAMP2 expressions may have a diagnostic and therapeutic value in the context of chronic inflammation and colorectal carcinogenesis.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and remains a major challenge in contemporary oncology, where early detection is critical for improving treatment outcomes and survival. Despite significant progress in diagnostics and therapy, the epidemiology, risk factors, and molecular mechanisms driving CRC development continue to be intensively investigated. This paper provides an overview of current trends in CRC diagnosis and management, with particular emphasis on advances in molecular medicine and biological sciences. Screening recommendations in Poland are discussed, comparing invasive methods—such as colonoscopy, sigmoidoscopy, and CT colonography—with non-invasive stool-based tests (FOBT, FIT, sDNA-FIT), and evaluating their sensitivity, specificity, and impact on mortality reduction. Key tumor markers with diagnostic, prognostic, and predictive value, including CEA, CA19-9, mSEPT9, ctDNA, TPS, TAG-72, CTCs, and circulating microRNAs, as well as p53 and PTEN proteins, are reviewed in the context of their clinical utility in early detection, disease monitoring, and treatment response assessment. The analysis also highlights the epidemiological situation in Poland and underscores the growing importance of integrating molecular biomarkers with traditional diagnostic methods, which may ultimately support the development of more precise and individualized clinical management strategies in the future.

Background/Objectives: Colorectal cancer (CRC) is one of the most common malignancies worldwide, with systemic inflammation increasingly recognised as a determinant of disease progression. This study aimed to establish a taxonomy-based classification of patients with newly diagnosed primary CRC using systemic inflammatory, haematological, and anthropometric markers, and to evaluate its association with tumour stage. Methods: A total of 229 patients (111 women, 118 men) undergoing surgery for primary CRC were included. Blood samples were analysed for haemoglobin, leukocytes, neutrophils, lymphocytes, platelets, C-reactive protein (CRP), and carcinoembryonic antigen (CEA). Anthropometric data were collected. Taxonomic clustering and ordinal logistic regression were used to explore associations with TNM and Astler–Coller classifications. Results: Men had higher neutrophil and leukocyte counts, elevated CEA concentrations (132.8 vs. 81.3 ng/mL), and higher NLR values (4.74 vs. 4.23) compared with women. Logistic regression confirmed that platelet count (OR 1.003; p = 0.004), PLR (OR 1.003; p = 0.003), and CEA (OR 1.03; p < 0.001) were positively associated with advanced TNM stage, while haemoglobin was inversely correlated (OR 0.88; p = 0.045). Among 84 clustering models, two taxonomies were the most clinically informative: Taxonomy I (BMI, neutrophils, platelets) and Taxonomy II (age, lymphocytes, platelets), both significantly associated with T, N, M, overall TNM stage, and Astler–Coller grade. Taxonomy I identified three patient groups. Type 3 represented the poorest phenotype, characterised by low BMI and haemoglobin, high platelets, elevated CEA and PLR, and predominance of TNM IIIC tumours, consistent with a cachectic–inflammatory profile. Type 1 displayed higher BMI, lower inflammation, and earlier-stage disease. Type 2 was characterized by elevated neutrophils and leukocytes. Taxonomy II distinguished four groups, with Type 2 demonstrating the most favourable profile (high haemoglobin and lymphocytes, low NLR and PLR, early TNM stage). Conclusions: Systemic inflammatory markers, haemoglobin, platelets, and CEA strongly predict CRC advancement. The proposed taxonomy provides clinically meaningful stratification of CRC patients and may support personalised risk assessment. This accessible approach may facilitate early identification of high-risk individuals, although validation in prospective studies is required.