Search Results (3,972)

Background: The Prognostic Nutritional Index (PNI), calculated from serum albumin and lymphocyte count, indicates nutritional and immunological status. Its prognostic significance in colorectal cancer (CRC) is still being assessed. Methods: This retrospective study examined 489 patients who received curative resection for colorectal cancer (CRC). According to ROC analysis, patients were split into two groups: those with low PNI (<47.5) and those with high PNI (≥47.5). We compared the clinicopathological features, postoperative outcomes, and survival rates. Kaplan–Meier and Cox regression models were used to look at overall survival (OS) and disease-free survival (DFS). Results: A low PNI was strongly related to older age, having a lower BMI, hemoglobin, albumin, and lymphocyte levels (all p < 0.001). The low-PNI group had a higher early hospital mortality (4% vs. 1%, p = 0.031). Patients with low PNI had a significantly lower five-year OS and DFS (both p < 0.001). In multivariate analysis, low PNI independently predicted poor OS (HR = 0.640, p = 0.016) and DFS (HR = 0.570, p = 0.037), in addition to pathological stage, age, and perineural invasion. Conclusions: Preoperative PNI serves as an independent prognostic marker for survival in CRC. A low PNI demonstrates that a patient has low nutritional and immune reserves, which means they are more likely to have worse early and long-term outcomes. Including PNI in preoperative evaluation may help with personalized treatment plans. Full article

Immunotherapy has demonstrated significant efficacy in colorectal cancer (CRC), but its therapeutic effects remain limited in microsatellite stable (MSS) patients, indicating the critical role of the tumor immune microenvironment (TIME) in regulating immune responses. Lipid rafts, dynamic membrane microdomains enriched in cholesterol and sphingolipids, have emerged as potential targets for TIME remodeling through their integration of immune signal transduction, enrichment of cell death receptors, and regulation of immune cell functionality. This review outlines the pivotal mediating roles of lipid rafts in cellular survival, death, and tumor progression. Specifically, MSS-type CRC exhibits lipid raft structural remodeling driven by dysregulated lipid metabolism, which fosters multiple immune escape mechanisms through exosome-mediated immunosuppressive signaling, promotion of tumor-associated macrophage (TAM) M2 polarization, enhanced infiltration of regulatory T cells (Tregs), and functional exhaustion of effector cells, such as CD8⁺ T cells and NK cells. Finally, we discuss targeted therapeutic strategies based on lipid raft characteristics and CRC molecular profiles, proposing an innovative multidimensional treatment framework combining immune checkpoint inhibitors with lipid raft-targeted interventions and chemoradiotherapy. This approach provides theoretical and strategic support for overcoming CRC immunotherapy resistance and advancing clinical translation. Full article

Background/Objective: Culturally adapted frailty screening tools are essential for improving health outcomes, facilitating clinical decision-making, promoting effective care planning, and ensuring accurate frailty assessment across diverse cultural contexts; their use among clinicians and academics is therefore supported. The purpose of this study was to assess internal consistency, test–retest reliability, and validity of the Arabic FRAIL scale (FRAIL-AR scale) for Arabic-speaking populations with colorectal cancer (CRC). Methods: This cross-sectional study included 137 participants diagnosed with CRC who completed the FRAIL-AR scale, the EORTC QLQ-C30 physical function subscale, and functional performance-based Timed Up and Go (TUG) and Five Times Sit-to-Stand (5xSTS) tasks. Internal consistency was assessed using Kuder–Richardson formula 20 (KR-20), and test–retest reliability was determined using the two-way random intraclass correlation coefficient ICC _(2.1). Convergent validity was evaluated by assessing the correlation between the FRAIL-AR scale against the EORTC QLQ-C30 physical function scale, TUG, and 5xSTS. Results: The FRAIL-AR scale exhibited good internal consistency (KR-20 = 0.80) and test–retest reliability (ICC _(2.1) = 0.89, 95% CI 0.77–0.94). Correlation analysis showed a weak negative correlation between the overall FRAIL-AR scale scores and EORTC QLQ-C30 physical function scale scores (r = −0.38, p < 0.05), while it exhibited a moderate positive correlation with TUG (r = 0.75, p < 0.01) and 5xSTS (r = 0.63, p < 0.01) scores. FRAIL-AR scores showed significant known-groups validity with higher frailty scores in older-age individuals (p < 0.01), females (p < 0.05), and those with comorbid conditions (≥5) (p < 0.05). Conclusion: The FRAIL-AR scale’s validity and reliability make it an appropriate tool for geriatricians, oncologists, and healthcare providers to evaluate and monitor frailty among Arabic-speaking colorectal cancer patients. Full article

Despite advances in blood-based screening tests for colorectal cancer (CRC), most existing assays focus on DNA-based biomarkers, which predominantly reflect tumor-derived fragments released at later disease stages. In contrast, whole-blood transcriptomic profiling can capture systemic immune responses and tumor–host interactions, offering a complementary strategy for earlier disease detection. However, clinically validated whole-blood transcriptomic signatures remain limited. Here, we investigated a whole-blood RNA-based biomarker discovery strategy by integrating multi-cohort transcriptomic resources. Public GEO datasets (GSE164191 and GSE11545) were harmonized and analyzed, yielding 956 differentially expressed genes (DEGs). Multi-layer biological filtering incorporating PPI networks, transcription factors, CRC-related GWAS variants, whole-blood eQTL signals, DigSeE, and CoReCG disease associations refined these to 375 high-confidence transcripts (WB-PADs). In parallel, RNA-seq analysis of a Korean cohort (10 CRC vs. 10 controls) identified 217 DEGs (WB-K). Cross-dataset convergence highlighted seven overlapping transcripts, and five candidates (DLG5, CD177, SH2D1B, NQO2, and KRT73) were selected for validation. RT-qPCR in an independent clinical cohort (106 CRC and 123 healthy controls) confirmed four transcripts with significant discriminatory ability. A multivariable logistic regression model derived from the five-transcript signature achieved an AUC of 0.952 (95% CI 0.884–1.000), with sensitivities of 0.889 and 0.667 at fixed specificities of 90% and 95%, respectively, demonstrating strong applicability for screening-relevant thresholds. Notably, the model retained high accuracy in early-stage CRC (Stage I–II: AUC 0.929, 95% CI 0.868–0.989). Overall, this study provides a robust analytic framework for reproducible whole-blood RNA biomarker discovery and establishes a multi-gene signature with promising translational potential for minimally invasive and early CRC detection. Full article

Background/Objectives: This study presents and explores the potential of Updated Bayesian Deduction (UBD) using colorectal cancer (CRC) detection and prioritisation as a case example. Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, and its prognosis strongly depends on early detection and timely treatment. In Chile, colonoscopy waiting lists for symptomatic patients in public hospitals can exceed one year, limiting access to early diagnosis and reducing survival rates. Traditional single-test screening strategies, such as a single faecal immunochemical test (FIT), often yield uncertain results, contributing to inefficiencies in resource allocation. Methods: We propose a new approach that integrates evidence from multiple sequential and independent FITs to dynamically update the posterior probability of CRC. A case study is analysed with this Updated Bayesian Deduction over a four-round FIT protocol to assess how this could improve risk stratification compared to standard symptoms-based screening. Results: Our mathematical model shows that over 85% of colonoscopies for symptomatic patients were not urgent. We then demonstrate that, if 4-FIT UBD were used to screen Chile’s Metropolitan Region population, only 96 out of 100,000 people would require an urgent colonoscopy to detect the 19.6 out of 100,000 individuals with CRC in this region. Many countries cannot afford a colonoscopy-based population screening, such as what is performed in Germany. Performing 4x FITs + a very small number of colonoscopies would be much more affordable and would get more countries to adopt general CRC screening. Conclusions: In countries with limited colonoscopy availability, such as Chile, where symptomatic patients can wait over a year for treatment in public hospitals, implementing a UBD-based strategy could drastically reduce costs and optimise the use of resources. This would improve access to colonoscopies for critical cases and ultimately enhance five-year survival rates. These findings highlight UBD as a promising approach for evidence-based precision medicine in CRC screening and prioritisation that is both explainable and adaptable. Full article

Colorectal carcinoma (CRC) represents the third most common cancer worldwide. Approximately 20% of patients present with metastatic disease at diagnosis, and 30–50% experience disease recurrence over time. For metastatic CRC (mCRC), the standard treatment consists of chemotherapy combined with a targeted agent based on molecular profile, such as RAS, BRAF, and MSI status. Anti-angiogenic drugs, which inhibit the formation of new blood vessels, have an established role in the management of mCRC. Mounting evidence highlights the critical interplay among angiogenesis, hypoxia, and the immune response in tumor progression. These insights have paved the way for testing novel combinations and molecules to control cancer progression. In particular, combining anti-angiogenic agents with immune checkpoint inhibitors has shown promise in improving outcomes for mCRC patients. Among emerging therapies, the novel anti-angiogenic agent fruquintinib has recently demonstrated clinical efficacy in the treatment of mCRC. Based on the data discussed in the present narrative review, the therapeutic landscape of mCRC appears poised for significant evolution in the near future. While numerous challenges and unanswered questions remain, the emergence of innovative therapeutic combinations and agents provides a promising opportunity for improving patient outcomes in mCRC. Full article

Despite the availability of conventional serum markers for colorectal cancer (CEA, CA 19-9), there remains a need for more sensitive and specific biomarkers, particularly for early-stage detection. This study evaluated the diagnostic usefulness of serum Relaxin-2 (RLN2) and Chitinase-3-like protein 1 (YKL-40) as potential adjunct markers in patients with CRC. Serum concentrations of all the proteins were measured using a multiplexing assay and CMIA and were subsequently compared using non-parametric statistical tests. The concentrations of YKL-40, CEA, and CA 19-9 were elevated in CRC patients relative to controls (p < 0.05), but not so for RLN2. The concentrations of YKL-40 were also significantly elevated in patients undergoing chemotherapy or preoperative radiotherapy referral. Kruskal–Wallis and post-hoc testing found that YKL-40 and CEA were associated with tumor progression, but RLN2 and CA 19-9 were increased primarily in advanced, metastatic disease. No statistically significant differences in marker levels were observed between cancer subtypes or between histologic grades. Performance analysis for diagnostic purposes showed YKL-40 was moderately sensitive (65%) but very specific (77.5%), and its AUC was 0.702, higher than CA 19-9 (AUC = 0.632) but lower than CEA (AUC = 0.869) (all p < 0.05). RLN2 did not reach statistical significance (AUC = 0.593, p = 0.09). Correlation analysis demonstrated the best correlation with disease stage for CEA and weaker positive correlations for YKL-40, CA 19-9, and RLN2. These findings suggest that YKL-40 may serve as a useful adjunct serum biomarker for CRC diagnosis, especially when combined with conventional markers such as CEA. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, and detecting circulating tumor cells (CTCs) is crucial for early diagnosis and metastasis monitoring. Conventional staining-based cytology is costly, time-consuming, and often compromises sample integrity. In this study, we employed a combined digital holography (DH) and fluorescence imaging approach to develop a virtual staining framework for transforming quantitative phase imaging (QPI) data into interpretable pseudo-stained images. To the best of our knowledge, this is the first application of such a framework to colorectal cancer CTC detection. In our experiments, green fluorescent protein (GFP)-labeled HCT116 cells—generated through lentiviral transfection—were mixed with peripheral blood mononuclear cells (PBMCs) to create training datasets. The trained network achieved 99% classification accuracy and demonstrated strong generalization to unseen donors. This DH–fluorescence-based virtual staining method preserves cell integrity while enabling rapid, label-free, and low-cost liquid cytology diagnostics, highlighting its potential for non-invasive cancer detection and monitoring. Full article

Background/Objectives: Colorectal cancer (CRC) exhibits significant molecular heterogeneity, as reflected in Consensus Molecular Subtype (CMS) classification, and demonstrates extensive crosstalk with the microbiome. However, the role of the microbiome in determining subtypes of CRC, and CMS4 in particular, which represents an aggressive, stromal-rich variant associated with poor prognosis, remains poorly understood. Here, we reveal the role of the tumor microbiome in shaping the tumor microenvironment (TME) and its impact on CMS4 determination. Methods: A total of 25 CRC tissues were analyzed using RNA sequencing and classified with CMScaller to identify significantly enriched microbial species. Functional studies were performed using these CMS-specific microbial species and CMS2 organoids co-cultured with stromal (18Co) and immune (THP-1) cells. Results: 16S rRNA profiling of matched CRC tissues showed that Bacteroides fragilis was significantly enriched in CMS4 tumors (linear discriminant analysis score = 4.7). Functional studies revealed that exposure to enterotoxigenic Bacteroides fragilis (ETBF) induced CMS4-like features, including enhanced growth and gene expression patterns resembling those of primary CMS4 tumors. Conclusions: These findings suggest that ETBF contributes to the development of CMS4 and may facilitate the acquisition of aggressive phenotype associated with this CRC subtype. Full article

Background: Endoscopic Electroporation (EE) is an innovative minimally invasive therapy that utilises short electrical pulses combined with intratumoural (IT) calcium or IT/intravenous (IV) chemotherapy to induce tumour cell death in colorectal cancer (CRC). Based on electrochemotherapy protocols developed for the treatment of skin cancers, EE has shown promising results in salvage therapy, local tumour control, and symptom palliation, particularly in patients who are unsuitable for surgery or standard treatments. Objective: To establish, for the first time, a comprehensive and standardised protocol for setting up a Salvage Endoscopic Electroporation (SEE) service in CRC clinical practice, covering multidisciplinary patient selection, procedural steps, equipment needs, and follow-up care. Methods: Drawing from the European Standard Operating Procedures of Electrochemotherapy (ESOPE) and emerging clinical evidence on EE from King’s College London, we detail infrastructure, treatment delivery, and monitoring for CRC. Key procedural elements, safety considerations, and patient management strategies are outlined. Electroporation pulses were delivered using the Conformité Européenne (CE) approved ePORE^® electroporation generator and single-use CE-marked EndoVE^® probe (Mirai Medical, Galway, Ireland). Results: Tumour assessment involves both clinical evaluation and endoscopic imaging, with radiological correlation. EE treatment has been safely carried out under sedation using specialised endoscopic probes, leading to effective local tumour response, symptomatic relief, and improved quality of life. Follow-up schedules allow for timely assessment of treatment response and enable repeat treatments if needed. Conclusions: This novel protocol provides a practical framework for centres aiming to implement SEE services, promoting consistency, safety, and better patient outcomes. Future prospective studies will refine indications and improve integration of this approach into colorectal cancer management pathways. Full article

Urolithin A (UA), a metabolite of dietary ellagitannins produced by the gut microbiome, is a potential dual-purpose bioactive compound that may interfere with the shared pathogenic pathways linking colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM). This review summarizes recent preclinical and clinical data on UA’s mechanisms, therapeutic potential, and translational challenges. In CRC models, UA promotes G2/M cell cycle arrest, triggers both intrinsic and extrinsic caspase-mediated apoptosis, enhances CD8+ T-cell mitophagy and memory functions, suppresses Wnt/β-catenin signaling, and reduces chemoresistance, especially to 5-FU. For T2DM, UA enhances autophagic flux, mitophagy, insulin signaling, and GLUT4-mediated glucose uptake through the AMPK and PI3K/AKT pathways, reduces fasting glucose and insulin resistance in animal studies, and promotes adipose tissue browning and mitochondrial beta-oxidation. Human biomarker research is limited but indicates positive changes following interventions that increase UA. Future priorities include biomarker-driven, dose-finding trials stratified by metabotype, developing colon-targeted vs. systemic formulations, and testing combinations with chemotherapy and immunotherapy to determine safety and effectiveness. Full article

Background: Cardiovascular disease (CVD) is a common cause of death among colorectal cancer (CRC) patients. We examined whether neighborhood disadvantage is associated with CVD mortality in CRC patients. Methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program for primary CRC patients diagnosed between 2006 and 2017. Neighborhood disadvantage was measured using the quintiles of the Yost Index, a socioeconomic composite measure. Cause-specific mortality (CVD-specific and CRC-specific mortality) was evaluated using a competing risk cause-specific hazard model, controlling for demographic and clinical covariates. Cumulative incidence function (CIF) and restricted mean survival time (RMST) analyses were performed to provide complementary estimates of absolute risk and survival differences. Results: The study included 316,549 patients with CRC. Cancer-specific mortality was the leading cause of death (62.1%), while CVD accounted for 9.6% of deaths. Multivariable competing risk Cox regression showed that the lowest-SES neighborhoods (Group 1) had a higher CVD-specific mortality (HR, 1.39; 95% CI, 1.30–1.48; p < 0.001) compared to the highest-SES neighborhoods (Group 5). RMST and CIF analyses revealed a similar dose–response pattern, with progressively higher CVD mortality associated with increasing levels of neighborhood disadvantage. Effect modification analyses indicated stronger associations in older patients and men, but no modifications by race. Conclusions: Among CRC patients, residing in disadvantaged neighborhoods was independently associated with higher CVD mortality, suggesting the importance of addressing cardiovascular risk in disadvantaged populations. Full article

Colorectal cancer (CRC) is the second most common global malignancy with high mortality, and timely early polyp detection is critical to halt its progression. Yet, polyp image segmentation—an essential tool—faces challenges: blurred edges, small sizes, and artifacts from intestinal folds, bubbles, and mucus. To address these, we proposed a novel segmentation model with multi-scale feature extraction. Its encoder uses Multiscale Attention-based Pyramid Vision Transformer v2 (PVTv2) for hierarchical features (lower-stage modules expand receptive field), while the decoder adopts a Parallel Multi-level Aggregation structure, plus multi-branch and improved reverse attention modules. Ablation experiments validated key modules. Compared to nine state-of-the-art networks across five benchmarks, the model showed superiority: optimal mDice/mIoU on polyp datasets, 0.2% higher mDice than MEGANet on Kvasir-SEG, and outperformance over UHA-Net and CSCA-U-Net on CVC-ClinicDB. Full article

Background: Multidrug resistance (MDR) remains a major obstacle in cancer chemotherapy, and overexpression of ABCB1 plays a critical role in the pathogenesis of MDR. Despite decades of research, significant clinical progress in the development of ABCB1 inhibitors has yet to be achieved. The small-molecule H89 is originally identified as an inhibitor of protein kinase A (PKA), but it also exhibits various functions unrelated to the PKA. This study investigates H89 as a novel ABCB1-inhibitor to reverse MDR in colorectal cancer (CRC). Methods: Cytotoxicity assays were performed on ABCB1-overexpressing MDR cell line HCT-8/V and parental CRC cell line HCT-8. Drug accumulation was quantified via flow cytometry, and cell cycle effects were analyzed using propidium iodide staining. The ATPase activity of ABCB1 was detected using an ATPase activity assay kit. Molecular docking utilized the ABCB1 crystal structure. Results: Both 3 μM and 10 μM H89 significantly reverses resistance to two ABCB1 substrate drugs (doxorubicin and vincristine) in HCT-8/V cells in a dose-dependent manner, with no such effect observed inHCT-8 cells. The combination of H89 and doxorubicin or vincristine resulted in a significant increase in the proportion ofHCT-8/Vcells in the sub-G1 and G2/M phases. Further mechanistic studies reveal that H89 exerts its effect by inhibiting the drug efflux function of ABCB1, thereby increasing the intracellular accumulation of the substrate drugs and reversing multidrug resistance. Furthermore, H89 did not alter the expression of ABCB1. H89 effectively inhibited the ATPase activity of ABCB1. Molecular docking simulations revealed the binding mode of H89 with ABCB1. Conclusions: The combination of H89 with ABCB1 substrate drugs significantly reverses multidrug resistance in colorectal cancer. These findings provide a strong theoretical and experimental foundation for the development of novel MDR-reversing agents targeting ABCB1. Full article

Background/Objectives: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that significantly increases the colorectal cancer (CRC) risk. This study used nationwide data on intractable diseases to clarify the clinical epidemiology of UC-related CRC in Japan. Methods: Patients diagnosed with UC between FY 2003 and 2011 were included. The relative incidence ratio (RR) was calculated using the standardized incidence ratio from the National Cancer Registry. To compare prognostic factors, outcomes were evaluated using the Cox proportional hazards model analysis for cancer occurrence, and a prognostic prediction model was developed using machine learning. Results: Among 78,556 patients with UC, CRC was identified in 141 patients. The RR of CRC peaked in both males and females in the 25–39 age group. Univariate analysis revealed several risk factors, including pseudo-polyps observed during endoscopy (hazard ratio 2.92, p = 0.001), abnormal crypt architecture (hazard ratio 3.14, p < 0.001), and dysplasia (hazard ratio 11.31, p < 0.001) in biopsy. Conversely, 5-ASA was associated with reduced CRC risk (hazard ratio 0.36, p = 0.003). The machine learning model categorized patients into three groups, demonstrating that the group with the highest number of patients with pancolitis had a significantly higher risk of CRC than did the other groups. Conclusions: Pseudo-polyps and dysplasia represent CRC risk factors in patients with UC. Additionally, machine learning analysis indicates that pancolitis in individuals in their 50s increases the risk of colon cancer, while proctitis in those in their 30s raises rectal cancer risk. These findings aim to enhance early detection and improve prevention efforts for UC-related CRC. Full article