Search Results (4,470)

Background/Objectives: OrganoHIPEC is a phase-II, two-stage, open-label clinical trial that investigates if cytoreductive surgery (CRS) and patient-tailored HIPEC, based on a preclinical platform using patient-derived organoids, can improve disease control in peritoneal metastases from colorectal cancer (CRC-PM). Methods: Adults with limited CRC-PM and no distant metastases were included. CRC-PM were sampled for organoid development during diagnostic laparoscopy. These organoids were used in an in vitro HIPEC model to test various drugs suitable for intraperitoneal administration. After 3–6 months of systemic chemotherapy, patients without progression underwent CRS/HIPEC with personalized regimens based on organoid drug response. To detect an increase in 12-month peritoneal disease-free survival from 40% to 60%, 24 patients are needed. According to the two-stage design, if <7 of 10 patients in Stage-1 remain PM-free at 12 months, the trial is terminated. Results: Forty-seven patients were enrolled. Among 31 patients with available organoid data, the most active drugs were mitomycin-C (n = 14), cisplatin/mitomycin-C (n = 12), and low-dose (120 min) oxaliplatin (n = 4). No patient was sensitive to high-dose oxaliplatin (30 min) and cisplatin/doxorubicin. Ten patients had a potential follow-up >12 months. Peritoneal relapse occurred at 8 months in two patients, and one died of liver metastases at 7 months. Seven patients remained PM-free for >12 months (median 16.4, range 12.6–28.4). Conclusions: A comprehensive precision approach using patient-derived organoids to guide personalized HIPEC is feasible and shows promising early results. High-dose oxaliplatin is poorly active. As 7/10 patients achieved the endpoint of 12-month PM-free survival, Stage-1 was successfully completed. The trial is proceeding to Stage-2. Full article

Colorectal cancer (CRC) progression is shaped by dynamic interactions between tumor-intrinsic metabolic adaptations and immune remodeling within the tumor microenvironment. In CRC, the expression of SMAD7, a classical inhibitor of TGF-β1 signaling, is increased and has been associated with tumor-associated inflammatory responses and malignant progression. In this study, we investigated the potential role of SMAD7 in regulating glycolytic metabolism and macrophage phenotype in CRC. Knockdown of SMAD7 in CRC cell lines resulted in reduced glycolytic activity, as demonstrated by decreased extracellular acidification rate, basal glycolysis, and glycolytic capacity. These metabolic changes were associated with reduced expression of the basal and IL-6- and IL-22-induced glycolytic enzyme hexokinase 2 (HK2), while glucose uptake was increased. Similar reductions in HK2 expression were observed in patient-derived CRC organoids following SMAD7 inhibition, supporting the relevance of this pathway in human tumor-derived models. Functionally, SMAD7 knockdown reduced lactate production by CRC cells and diminished the ability of tumor cell-derived conditioned medium to induce the expression of macrophage-associated immunoregulatory markers, including CD163, CD206, and ARG1. The addition of exogenous lactate restored these effects, indicating that tumor-derived lactate contributes to SMAD7-dependent control of the expression of macrophage-associated immunoregulatory markers. Analysis of human CRC transcriptomic datasets revealed positive associations between SMAD7 expression and macrophage-related signatures, including profiles associated with immunoregulatory tumor-associated macrophages. Together, these findings support a potential role for SMAD7 in controlling tumor metabolism and macrophage-associated immunoregulatory markers in CRC. Full article

Machine learning and statistical classification methods are widely applied to microbiome data for diagnostic, prognostic, and phenotypic insights. However, the complex, multivariate nature of microbiome communities makes it difficult to assess the relative performance of these methods. Most comparisons rely on a small number of published datasets, without considering their underlying ecological properties or how these properties may, in turn, influence classification performance. We introduced a coenocline-based simulation framework to generate synthetic microbiome datasets that incorporate realistic ecological variation arising from species’ responses to host-associated gradients such as disease severity. To evaluate the ecological fidelity of these simulations, we compared synthetic datasets to five widely used real-world microbiome datasets: Cirrhosis, Colorectal Cancer (CRC), Type 2 Diabetes (Chinese and Women cohorts), and the Human Microbiome Project (HMP). Comparisons across α-diversity (species richness), β-diversity (species composition and turnover), and abundance distributions demonstrated that coenocline simulations closely recapitulate the key ecological structures of empirical data. Synthetic datasets exhibited similar richness and abundance patterns to disease-associated microbiomes, with realistic distributions of few dominant and many rare taxa. Moreover, community composition analyses (Bray–Curtis index) revealed that the simulated datasets captured natural levels of compositional dissimilarity among samples, spanning the same variability range observed in real data. When compared against 100 independently simulated datasets, the coenocline model consistently reproduced empirical ranges of species diversity, relative abundance, and between-group compositional differences (ANOSIM-R values), confirming the model’s robustness and reproducibility. This coenocline-based simulation framework provides a novel, flexible, and ecologically grounded approach for generating synthetic microbiome data with controlled complexity. By reproducing realistic ecological gradients and community structures, the framework supplies the controlled test beds needed for systematic future benchmarking of machine learning and statistical classification methods across diverse and biologically meaningful scenarios. In doing so, it will help bridge the gap between ecological realism and computational modeling, thereby supporting more reliable and generalizable inference from microbiome data. Full article

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-associated mortality worldwide. The current therapeutic interventions are heavily constrained by the development of resistance and severe systemic toxicity. To address these challenges, this study integrated a multi-disciplinary framework involving high-throughput in silico screening followed by in vitro experimental validation to identify novel genetic targets of CRC and evaluate the efficacy of FDA-approved drugs. The primary objective was to identify safe and selective therapeutic agents capable of modulating their effect. Methods: The methodology employed a systematic screening of recent large-scale Genome-Wide Association Studies (GWASs) to pinpoint novel targets, followed by in silico pathogenicity prediction, homology modelling and high-throughput virtual screening of over 1615 FDA-approved drugs. The prioritized candidates were validated in vitro using MTT cytotoxicity assays and differential gene expression analysis across CRC cell lines (HCT116 and HT29) and a non-tumorigenic control, Human embryonic kidney cell line HEK293. Results: In silico analysis identified CLUH, CLSTN3 and SLC11A2 as novel potential targets. Based on in silico predicted deleterious mutations and subsequent molecular docking-based virtual screening, Telmisartan, Dutasteride and Venetoclax were prioritized. This prioritization was supported by their high binding affinity and dose-dependent cytotoxicity in MTT assays; thus, suggesting their repurposing potential for CRC treatment. Telmisartan exhibited a superior therapeutic profile not only in terms of the statistically significant cytotoxicity (p < 0.01), but also its selective effect on HCT116 and HT29 when compared to high safety profile in HEK293. This was further validated when Telmisartan selectively downregulated CLUH and SLC11A2 in CRC cell lines, HCT116 and HT29 while maintaining expression levels in the non-cancerous HEK293 cell line remained significantly unaffected. Furthermore, a 100 ns molecular dynamics simulation confirmed the stable binding conformation and structural reliability of the SLC11A2 (Trp179Ser)–Telmisartan complex. Conclucions: Our findings conclude that Telmisartan is a promising candidate for drug repurposing for CRC treatment and capable of modulating selected novel biomarkers CLUH and SLC11A2. However, further multi-omics-based confirmatory studies and pre-clinical validation studies are needed in the future to confirm the long-term efficacy of this repositioning strategy. Full article

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. Full article

Background: In recent decades, the incidence of colorectal cancer (CRC) has been rising worldwide. CRC ranks second in cancer-related mortality. The identification of reliable biomarkers for early diagnosis and prognosis prediction, along with a deeper understanding of the underlying molecular events, holds substantial promise for improving patient outcomes. The tissue inhibitor of the metalloproteinase 1 (TIMP1) gene is overexpressed in various gastrointestinal malignancies and contributes to tumor progression. However, its role in regulating the CRC tumor immune microenvironment (TIME) and its potential as a clinically actionable prognostic biomarker remain unclear. Methods: To probe how TIMP1 acts as a prognosis-related candidate biomarker in colorectal carcinoma, TCGA-derived datasets were adopted to conduct Kaplan–Meier survival assessment. We also investigated the connection between the expression abundance of TIMP1 and the infiltration of immune populations and intratumoral lymphocytes; furthermore, immune checkpoint-related genes were systematically assessed across multiple tumor types via the TISIDB and TIMER2.0 platforms, with particular emphasis on CRC. We adopted the ESTIMATE scoring system to figure out how TIMP1 gene expression correlates with the phenotypic properties of the colorectal-cancer TIME. We relied on the limma toolkit for the screening of differential transcripts from high-TIMP1 and low-TIMP1 cohorts. Enrichment assessments covering Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes entries were then carried out to predict the potential biological pathways associated with TIMP1. We constructed the protein–protein interaction map for TIMP1-interacting partners via the STRING repository. To further explore TIMP1-correlated genes, we performed Venn diagram intersection analysis combined with Spearman’s correlation test. Finally, quantitative reverse-transcription PCR was then implemented to detect TIMP1 messenger-RNA abundance inside the RKO colorectal carcinoma cell line as well as normal colonic epithelial CCD-18Co cells, which offered in vitro experimental verification for our bioinformatic outcomes. Results: According to outcome data, TIMP1 transcripts were markedly up-regulated in CRC specimens and cell lines relative to normal samples. Elevated TIMP1 expression served as a poor-prognosis indicator for overall survival (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.29–0.64, p < 0.001) and disease-specific survival (HR = 0.39, 95% CI = 0.22–0.68, p = 0.001) among colorectal-carcinoma patients. TIMP1-high and TIMP1-low groups exhibited notable differences in immune cell infiltration (CD8⁺ T, macrophage, mast, neutrophil, B, monocyte, dendritic, and CD4⁺ T cells). TIMP1 expression was also significantly correlated with tumor-infiltrating lymphocytes, key immune checkpoint genes (e.g., CD274 [PD-L1] and CTLA4), and immunomodulatory chemokines (e.g., CCL3 and CCL5). Twelve TIMP1-interacting DEGs were selected: COL5A1, FN1, PRG4, and a cluster of nine MMPs (MMP1/2/3/7/8/9/11/13/14), all of which showed significant positive correlations with TIMP1 (r = 0.31–0.63, all p < 0.001). Conclusions: TIMP1 expression correlates with features of the tumor immune microenvironment and extracellular matrix remodeling in CRC, suggesting that TIMP1 shows potential as a candidate biomarker. However, its potential as a therapeutic target warrants further experimental investigation. Full article

Cancer metastasis, characterized by the dissemination of malignant cells from the primary tumor to distant organs, remains the leading cause of cancer-related mortality in solid tumors. In colorectal cancer (CRC), increasing attention has been directed toward therapeutic strategies aimed at suppressing cancer cell migration and invasion rather than solely reducing tumor mass, giving rise to the concept of migrastatic therapies. In the present study, green-synthesized silver nanoparticles (AgNPs), previously obtained using aqueous extracts of Filipendula ulmaria (L.) Maxim. and Salvia verticillata L., were evaluated for their antimigratory and anti-inflammatory potential in human colorectal carcinoma HCT-116 cells. Treatment with AgNPs induced considerable perturbations in cellular redox homeostasis, as evidenced by increased intracellular reactive oxygen species (ROS), lipid peroxidation (LPO), glutathione (GSH), and nitric oxide (NO) levels. These redox alterations were accompanied by a significant inhibition of cancer cell migration, together with reduced expression of matrix metalloproteinases MMP-2 and MMP-9, key mediators of extracellular matrix remodeling associated with tumor progression. AgNP exposure was associated with activation of the cytoprotective transcription factor Nrf-2 and suppression of the pro-inflammatory NF-κB/COX-2 signaling axis, indicating coordinated modulation of redox-sensitive pathways linked to tumor cell motility and inflammatory responses. Collectively, these findings demonstrate that green-synthesized AgNPs derived from F. ulmaria and S. verticillata exert multi-level regulatory effects on redox balance, inflammatory signaling, and migration-associated molecular markers in colorectal cancer cells. This study supports their potential as promising migrastatic nanocarriers for further investigation in colorectal cancer research. Full article

Background/Objectives: Metastatic colorectal cancer (mCRC) remains difficult to treat, largely due to chemotherapy resistance. Mutations in TP53 impair apoptosis and are associated with poor response to irinotecan. This study aimed to determine whether targeting Survivin, a key inhibitor of apoptosis, and using the disulfiram-derived compound CuET could restore apoptotic signaling and improve irinotecan efficacy. Methods: Human CRC cell lines with varying TP53 status and murine tumor models were treated with irinotecan (or its active metabolite SN-38), the Survivin inhibitor YM-155, and CuET, alone or in combination. Cell viability, clonogenic survival, and apoptotic signaling were assessed using cytotoxicity assays, flow cytometry, confocal microscopy, and Western blotting. In vivo efficacy was evaluated in xenograft and syngeneic mouse models through tumor growth measurements and histological analyses. Results: Inhibition of Survivin with YM-155 enhanced irinotecan-induced cytotoxicity and promoted caspase-dependent apoptosis in CRC cells. Irinotecan treatment induced Survivin expression, suggesting an adaptive resistance mechanism that was reversed by YM-155. CuET demonstrated potent cytotoxic activity independent of TP53 status and partially suppressed Survivin expression. Importantly, CuET restored sensitivity to irinotecan in TP53-deficient models and significantly enhanced antitumor efficacy in vivo, leading to reduced tumor growth, decreased proliferation, and increased apoptosis. Conclusions: These findings identify Survivin-mediated apoptotic resistance as a key determinant of irinotecan response in CRC. Targeting this pathway, either directly through Survivin inhibition or through CuET-induced stress responses, restores apoptotic sensitivity and enhances chemotherapy efficacy. This study supports the development of combination strategies incorporating CuET to overcome resistance in TP53-mutant CRC. Full article

Background: Family caregivers play a central role in supporting people with colorectal cancer (CRC) and often manage complex physical, emotional, and practical demands. However, evidence regarding their experiences and supportive care needs in Kazakhstan remains limited. This qualitative study explored caregiving experiences, caregiving burden, caregivers’ needs, and coping strategies. Methods: A qualitative descriptive design was used, involving semi-structured interviews with 21 family caregivers caring for patients with CRC. Participants were recruited purposively from the Medical Center of West Kazakhstan Marat Ospanov Medical University and outpatient clinics in Aktobe between December 2025 and March 2026. Interviews were audio-recorded, transcribed verbatim, and analyzed using inductive reflexive thematic analysis. Results: Most family caregivers of patients with colorectal cancer were women (95.2%). Five main themes developed: emotional challenges, transformation of daily life, caregiving tasks, caregivers’ needs and support gaps, and coping strategies and resilience. Diagnosis was described as a distressing experience characterized by shock, fear, and uncertainty. Caregiving substantially disrupted employment, financial stability, and family roles, often requiring work adjustment or leaving the workforce. Caregivers reported insufficient preparation for stoma care and expressed a strong need for structured training. Social isolation was common, as both caregivers and patients experienced a shrinking of their social support networks. Despite substantial burden, caregivers described adaptive responses to ongoing emotional and practical demands, and resilience was a prominent theme. Conclusions: Family caregivers of patients with colorectal cancer in Kazakhstan face interconnected emotional, informational, physical, and system-level challenges, while also drawing on resilience. The findings highlight priorities for support, including structured stoma care education, psychological services, recognition of caregivers’ roles, and improved discharge and transitional care. Full article

Background: Emergency surgery for complicated colorectal cancer (CRC) presenting with obstruction, perforation, or uncontrolled bleeding has high postoperative mortality, especially in older patients. However, age-related risk and the roles of radical versus palliative treatment are not fully understood. This study aimed to measure 90-day and 36-month mortality after emergency CRC surgery and to analyze whether the relationship between age and mortality is nonlinear and influenced by operative intent. Methods: Retrospective cohort of consecutive adults undergoing emergency surgery for complicated CRC (2015–2024). The outcome was 90-day and 36-month all-cause mortality. Cox regression provided adjusted hazard ratios (HR) using two models: a primary whole-cohort model omitting pathological T/N stage, and a secondary resection-only model including pathological stage. Age was modeled with restricted cubic splines and predicted 90-day and 36-month mortality were plotted by operative intent. Results: In 496 patients, 90-day mortality was 19.7% (98/496), while 36-month mortality was 37.3% (185/496). In the primary whole-cohort Cox model, independent predictors of 36-month mortality included age ≥75 years (HR 2.09, 95% CI 1.48–2.95, p < 0.001), Charlson Comorbidity Index (HR 1.02, 95% CI 0.98–1.06, p = 0.31), obstruction (HR 1.69, 95% CI 1.18–2.42, p = 0.004), perforation (HR 2.05, 95% CI 1.24–3.39, p = 0.005), and metastatic disease (HR 2.30, 95% CI 1.62–3.27, p < 0.001); radical operative intent was independently associated with lower 36-month mortality (HR 0.461, 95% CI 0.30–0.71, p = 0.001). In a secondary resection-only model additionally adjusting for pathological T/N stage (n = 426 with available pathology), the association for radical intent was attenuated and no longer statistically significant (HR 0.67, 95% CI 0.43–1.03, p = 0.067). The 36-month mortality spline estimate indicated an increasing risk with advancing age; a likelihood-ratio test did not show that the spline model fit significantly better than a linear age term (χ² = 1.43, df = 1, p = 0.233), so this pattern is interpreted descriptively rather than as formal evidence of nonlinearity, and no formal interaction between age and operative intent was demonstrated. Conclusions: Ninety-day mortality after emergency colon cancer surgery remains significant. Age-related risk shows a predominantly monotonic, descriptive pattern and should not be assumed to vary by operative intent without formal interaction testing, emphasizing individualized risk assessment and shared decision-making. Full article

Background/Objectives: Chemerin is an adipokine implicated in metabolic regulation, inflammation and cancer biology, but its value as a circulating biomarker in colorectal neoplasia remains uncertain. We investigated serum chemerin concentrations in patients with colorectal cancer (CRC), patients with colorectal polyps and colonoscopy-negative controls, and explored chemerin immunoreactivity in available polyp and tumour tissue. Methods: This exploratory observational case–control study included 41 patients with CRC, 20 patients with colorectal polyps and 29 colonoscopy-negative controls. Serum chemerin was measured by ELISA. Tissue specimens underwent routine histopathology and qualitative immunohistochemical staining for chemerin. Between-group comparisons were performed using non-parametric tests; subgroup analyses were exploratory and unadjusted. Results: Serum chemerin concentrations did not differ significantly between CRC and controls (median 144.0 vs. 135.7 ng/mL; p = 0.41), CRC and polyp groups (144.0 vs. 97.4 ng/mL; p = 0.24), or polyp and control groups (97.4 vs. 135.7 ng/mL; p = 0.94). Chemerin immunostaining was absent in CRC tissue (0/41) and conventional adenomatous polyps (0/15), whereas all available hyperplastic/serrated lesions showed epithelial cytoplasmic and/or stromal immunoreactivity (5/5); in lesions containing dysplasia, dysplastic glands showed no detectable staining. In controls, higher chemerin concentrations were associated with hyperglycaemia, hypertension, body weight and bilirubin, but these exploratory findings were not adjusted for multiplicity or metabolic confounding. Conclusions: In this exploratory cohort, serum chemerin did not discriminate CRC or colorectal adenoma from colonoscopy-negative controls. Together with the absence of staining in CRC and conventional adenomas, the findings argue against chemerin as a standalone circulating or commonly expressed tissue biomarker for these lesions under the assay conditions used. Immunoreactivity in the non-dysplastic epithelial and/or stromal compartments of hyperplastic/serrated lesions remains preliminary and requires prospective confirmation with standardised pre-analytics, quantitative pathology scoring and adjustment for metabolic confounders. Full article

Perioperative treatment for colorectal cancer (CRC) is undergoing a paradigm shift from uniform cytotoxic regimens toward strategies guided by tumor location, microsatellite instability (MSI)/mismatch repair (MMR) status, and recurrence risk. Four clinically relevant subgroups now shape decision-making: microsatellite stable (MSS)/proficient MMR (pMMR) colon cancer, microsatellite instability-high (MSI-H)/deficient MMR (dMMR) colon cancer, MSS/pMMR rectal cancer, and MSI-H/dMMR rectal cancer. In MSS/pMMR colon cancer, adjuvant therapy is being refined through risk-adapted treatment duration and selective use of neoadjuvant chemotherapy. In MSS/pMMR rectal cancer, total neoadjuvant therapy, selective omission of pelvic radiotherapy, and watch-and-wait strategies are redefining treatment sequencing and organ preservation. In MSI-H/dMMR colon cancer, immune checkpoint inhibitor (ICI) therapy has shown marked activity in both adjuvant and neoadjuvant settings. In MSI-H/dMMR rectal cancer, neoadjuvant ICI therapy is being explored as a non-operative organ preservation strategy. In parallel, circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) assessment is emerging as a tool for postoperative escalation, de-escalation, and surveillance. Across these settings, the maturity of the evidence varies widely, ranging from established phase III standards to guideline-endorsed but still single-arm approaches and investigational strategies that require prospective validation before routine adoption. This review summarizes the current evidence and remaining challenges in biology-, site-, and risk-adapted perioperative management of CRC. Full article

Fenjiu distillers’ grains are a major by-product of Fenjiu production and contain various bioactive components derived from cereal raw materials and microbial fermentation. Colorectal cancer (CRC) remains a global health challenge, and the development of safe and effective therapeutic agents is urgently needed. In this study, we successfully obtained DGAE-1 (distillers’ grains ethanol extract fraction 1), an ethanol-extracted bioactive fraction derived from Fenjiu distillers’ grains, with anti-colorectal cancer activity. LC-MS analysis tentatively annotated the chemical constituents of DGAE-1 fraction based on MS/MS fragmentation patterns and database similarity matching, with the major annotated compounds belonging to carboxylic acids and derivatives, organic nitrogen compounds, organic phosphoric acid derivatives, and other chemical classes. These annotated compounds may contribute to the biological activity of DGAE-1 fraction, although the specific active constituents remain to be further clarified. DGAE-1 fraction inhibited colorectal cancer cell proliferation and induced autophagy. Further studies indicated that the PI3K/AKT pathway is involved in DGAE-1 fraction-induced autophagy. The results of this study demonstrate that DGAE-1 fraction exerts anti-colorectal cancer activity in both cellular and animal models. These findings provide new insights into the development and utilization of Fenjiu distillers’ grains and highlight their potential as a source of bioactive compounds for health-related applications. Full article

Background/Objectives: Colorectal cancer (CRC) remains a major contributor to the global oncological burden, with marked disparities in mortality and survival between Western and Eastern European countries. Romania continues to report unfavorable CRC outcomes, driven by delayed diagnosis, limited screening uptake, and heterogeneous care pathways. This study aimed to assess the 15-year institutional description of colorectal cancer case-mix in South-West Oltenia, Romania, using real-world data from a high-volume oncology referral center. Methods: We conducted a retrospective observational study including 3497 patients with newly diagnosed CRC registered between 2011 and 2025. Sociodemographic characteristics, tumor localization, stage at diagnosis, and histopathological grade were analyzed. Temporal patterns were assessed across three five-year intervals. Results: The institutional CRC case volume increased, with 434 cases recorded in 2011–2015, 1015 in 2016–2020, and 2048 in 2021–2025. Male patients accounted for 60.5% and urban residents for 60.3% of cases. Early-onset CRC was identified in 12.0% of patients, with no significant temporal trend. Rectosigmoid junction/rectal cancers represented the largest anatomical group, followed by left-sided cancers, with stable distribution across periods. Advanced stage disease was frequent, with 77.1% of patients diagnosed in stage III–IV, increasing from 67.7% to 82.0% across study intervals (p < 0.001). Histopathological grade changed significantly (p < 0.001), due to a progressive increase in unspecified grade, from 16.1% to 45.5%. Conclusions: Colorectal cancer represents a substantial institutional workload at this regional referral center, emphasizing the need for strengthened early detection strategies, optimized referral system, improved diagnostic access, and standardized pathological reporting practices. Full article

In colorectal cancer (CRC), tumor progression is influenced by immunosuppressive tumor microenvironment (TME), in which innate immunity and adaptive immunity play an important role. CD47 is one of the key molecules in the process. It sends a “don’t eat me” signal to macrophages by binding to signal regulatory protein alpha (SIRPα), thus helping tumor cells escape immune clearance. Forkhead box P3 (FOXP3)⁺ regulatory immune cells further suppress antitumor T-cell responses. Here, based on a review of the literature and publicly available transcriptomic data, we propose that CD47 expression and FOXP3⁺ regulatory T cells in CRC are interconnected components of a broader myeloid–regulatory immunosuppressive phenotype, rather than a simple linear CD47–FOXP3 pathway. Evidence from cancer studies and exploratory GEPIA3/TIMER3.0 analyses supports a weak and method-dependent association between CD47 expression, FOXP3 transcripts, and estimated Treg infiltration. Hippo/Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) signaling serves as a potential upstream program contributing to this immune context. Full article