Search Results (1,254)

Colorectal cancer (CRC) is a significant public health issue, representing one of the greatest causes of both cancer diagnosis and mortality globally. While the incidence is highest in high-income countries, it is rising across the world, including in the Middle East and North Africa (MENA) region. Many countries have implemented national screening programmes to reduce the burden of CRC, utilising mostly stool tests and colonoscopy, but this has yet to occur across most MENA countries. Uptake of screening opportunities is generally poor. System-level barriers to establishing screening programmes include cost constraints and limited screening infrastructure. Patient-level barriers include embarrassment, fear of a cancer diagnosis, and limited awareness/education. Screening programmes across the MENA region would likely reduce the CRC incidence. These barriers must be overcome through patient education and government action to ensure appropriate patient uptake. This study aims to examine CRC screening practices across MENA, identify key barriers, and propose solutions for sustainable CRC management in the region, through a narrative review and expert input from the Middle East and North Africa Colorectal Cancer (MENA-CRC) Screening and Prevention collaborators. Full article

Fermentation represents a sustainable biotechnological approach for enhancing bioactive properties of plant-based foods, yet its anticancer effects remain underexplored. We evaluated the antiproliferative activity of fermented (with commercial probiotic lactic acid bacteria consortium) and unfermented plant-based beverages derived from tiger nut, carob, and rice using an in vitro model. Following INFOGEST 2.0 gastrointestinal digestion, bioaccessible fractions were applied to Caco-2 colorectal adenocarcinoma cells at 1:15 v/v dilution for 24 h. Analyses included cell viability, apoptosis detection, cell cycle distribution, reactive oxygen species production, glutathione content, mitochondrial membrane potential, and intracellular calcium levels. Fermented tiger nut achieved superior (p < 0.05) cytotoxicity compared to unfermented counterpart (39.6% vs. 77.4% cell viability) through dual mechanisms: depleting cellular antioxidant defenses (glutathione reduced to 55.9%) while inducing oxidative stress (180.3% ROS overproduction). This evoked irreversible apoptosis (76.9% early apoptosis) and extensive DNA fragmentation (84.8% SubG₁ population) via calcium-independent pathways. Fermented carob operated through cytostatic mechanisms, inducing G₀/G₁ cell cycle arrest (74.7% vs. 44.2% in blank digestion cells) without oxidative stress. Fermentation reduced (p < 0.05) rice beverage antiproliferative activity (90.2% vs. 71.9% unfermented beverage cell viability). These findings establish lactic acid fermentation as effective for developing plant-based beverages with anticancer mechanisms, offering dietary strategies for colorectal cancer prevention. Full article

Lateral Spreading Tumors (LSTs) are a type of non-polypoid lesion known for their flat morphology, which often leads to them going undetected. However, especially nongranular (NG) LSTs have the potential for malignant transformation. Recent advances in endoscopic technologies have improved the detection of these lesions. Despite growing research interest in their role in colorectal cancer (CRC) development, a comprehensive molecular characterization of LSTs is still lacking. The aim of this review is to highlight the current knowledge of the molecular characteristics of LSTs, that may help in determining whether LSTs can be prognostic indicators and identifying cases where they may rapidly progress to CRC through characteristic molecular pathways. From a mutational point of view, LSTs seem to be more closely associated with inflammatory bowel diseases (IBDs) than with polypoid lesions. Nonetheless, they have peculiar epigenetic and genetic traits, which set them apart from other adenomas or bowel diseases. Elucidating their role in CRC development would provide benefits for their classification and management, by enhancing clinical surveillance strategies for patients diagnosed with these lesions in order to improve the efficient prevention of colorectal cancer. Full article

Colorectal cancer is one of the three most common cancers worldwide. Early detection and assessment of polyps can significantly reduce the risk of developing colorectal cancer. Physicians can obtain information about polyp regions through polyp segmentation techniques, enabling the provision of targeted treatment plans. This study systematically reviews polyp segmentation methods. We investigated 146 papers published between 2018 and 2024 and conducted an in-depth analysis of the methodologies employed. Based on the selected literature, we systematically organized this review. First, we analyzed the development and evolution of the polyp segmentation field. Second, we provided a comprehensive overview of deep learning-based polyp image segmentation methods and the Mamba method, as well as video polyp segmentation methods categorized by network architecture, addressing the challenges faced in polyp segmentation. Subsequently, we evaluated the performance of 44 models, including segmentation performance metrics and real-time analysis capabilities. Additionally, we introduced commonly used datasets for polyp images and videos, along with metrics for assessing segmentation models. Finally, we discussed existing issues and potential future trends in this area. Full article

Background: Early detection and prevention of colorectal cancer (CRC) are key goals of population-based screening. Several diagnostic tests have been proposed for CRC screening. This study compares the diagnostic accuracy of colon capsule endoscopy (CCE), colonoscopy (COL) and computed tomographic colonography (CTC), focusing on risk factors such as polyps. Methods: We conducted a systematic review with meta-analyses and network meta-analysis. Pooled estimates of sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) were calculated using a random-effects model. Diagnostic performance was assessed for first- and second-level screening based on effect size estimates. Results: For first-level screening, sensitivity was 0.79 (95% CI: 0.60–0.91) and specificity 0.95 (95% CI: 0.88–0.98); PPV and NPV were 0.89 and 0.97, respectively. In second-level screening, sensitivity was 0.75 (95% CI: 0.65–0.83), specificity 0.95 (95% CI: 0.92–0.97), PPV 0.76 and NPV 0.95. The indirect sensitivity estimate of CCE vs. COL (SMD = 0.30; 95% CI: 0.12–0.47) was lower than the direct estimate for CTC (SMD = 0.44; 95% CI: 0.29–0.59). CCE showed better comparative performance than CTC relative to COL (CCE SMD = −0.18; 95% CI: −0.29 to −0.06 vs. CTC SMD = −0.98; 95% CI: −1.07 to −0.90). However, both CCE and CTC had lower specificity than COL. Conclusions: CCE represents a valuable tool for early CRC detection. Test selection should be guided by clinical and epidemiological settings to optimize screening strategies. Full article

Ulcerative colitis (UC) is associated with an elevated risk of colorectal cancer (CRC), driven by chronic inflammation and a distinct inflammation–dysplasia–carcinoma pathway. Conventional surveillance relies on colonoscopy and histologic assessment, but flat, multifocal dysplasia and sampling limitations challenge early detection. Tissue-based biomarkers offer promise in improving risk stratification and identifying patients at high risk for UC-associated CRC (UC-CRC). This review explores key categories of tissue biomarkers with potential clinical utility, including genetic mutations, epigenetic alterations, microRNA expression profiles, and markers of genomic instability such as telomere shortening, copy number variants, and aneuploidy. Many of these molecular alterations precede histologic dysplasia and reflect a “field effect,” suggesting their potential role in early cancer detection. Despite compelling associations between these biomarkers and neoplastic progression, most lack prospective validation and are not yet ready for routine clinical use. Future research should prioritize the development of integrated biomarker panels and validate their predictive accuracy in longitudinal UC cohorts. Molecular profiling may ultimately enable personalized, risk-adapted surveillance strategies that improve early detection while minimizing unnecessary interventions. Full article

Background/Objectives: Aristolochia ringens, a medicinal plant widely used in traditional medicine, has shown potential therapeutic applications. This study aimed to investigate the anticancer mechanism of action of its crude extract against human colorectal adenocarcinoma cells (Caco-2 and HT-29). Methods: Cell viability was assessed using the MTT assay to determine IC₅₀ values. Immunofluorescence microscopy was used to examine nuclear morphology and microtubule integrity. Flow cytometry with PI staining was used for cell cycle analysis and Annexin V-FITC/PI staining for apoptosis detection. Mitochondrial membrane potential was evaluated using JC-1 dye. Bioactivity-guided fractionation was performed via HPLC, and GC–MS was used to profile active constituents. Results: The extract exhibited dose-dependent cytotoxicity with IC₅₀ values below 30 µg/mL in colon adenocarcinoma cell lines. Treated Caco-2 cells showed nuclear shrinkage and disrupted microtubules. PI-based flow cytometry revealed G₁ phase arrest, and Annexin V-FITC/PI staining indicated enhanced late apoptosis. JC-1 staining demonstrated mitochondrial depolarization. HPLC fractionation identified fractions 2 and 3 as active, and preliminary GC–MS analysis tentatively annotated the presence of alkaloids, sesquiterpenes/diterpenes, and steroidal compounds. Conclusions: A. ringens exerts anticancer effects through a mitochondria-mediated apoptotic pathway, involving G₁ checkpoint arrest and cytoskeletal disruption. These findings provide the first integrated cellular and mechanistic evidence of its anticancer potential in colorectal cancer, supporting its promise as a source of novel therapeutic lead compounds. Full article

Background: Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, emphasizing the urgent need for early, non-invasive, and accessible diagnostic tools. This study aimed to evaluate the effectiveness of a microelectromechanical systems (MEMS)-based electronic nose (E-nose) in combination with gas chromatography–mass spectrometry (GC-MS) for CRC detection through sweat volatile organic compounds (VOCs). Methods: A total of 136 sweat samples were collected from 68 volunteer participants. Samples were processed using solid-phase microextraction (SPME) and analyzed by GC-MS, while a custom-designed E-nose system comprising 14 gas sensors captured real-time VOC profiles. Data were analyzed using multivariate statistical techniques, including PCA and PLS-DA, and classified with machine learning algorithms (LDA, LR, SVM, k-NN). Results: GC-MS analysis revealed statistically significant differences between CRC patients and healthy controls (COs). Cross-validation showed that the highest classification accuracy for GC-MS data was 81% with the k-NN classifier, whereas E-nose data achieved up to 97% accuracy using the LDA classifier. Conclusions: Sweat volatilome analysis, supported by advanced data processing and complementary use of E-nose technology and GC-MS, demonstrates strong potential as a reliable, non-invasive approach for early CRC detection. Full article

Background/Objective: At least 25% of colorectal cancer (CRC) patients develop liver metastases (CRLM), and chemotherapeutic regimens based on the fluoropyrimidine (FP) drug 5-fluorouracil (5-FU) provide a survival advantage, but long-term survival is uncommon. The primary molecular target of FP drugs is thymidylate synthase (TS). Methods: A TS/Top1 dual-targeting cytotoxic mechanism for CF10/LV was confirmed by TS ternary complex detection by Western blot and by immunofluorescence detection of Top1 cleavage complexes. CF10/LV activated the ATR/Chk1 pathway consistent with enhanced replication stress and induced apoptosis. In vivo studies showed CF10 and CF10/LV eradicated liver metastasis in a CRLM model without scarring or weight loss, displaying therapeutic advantages relative to legacy FPs. Results: We demonstrated that a nanoscale FP polymer, CF10, displayed greater potency than expected based on FP content in part through more direct conversion to the TS-inhibitory metabolite, FdUMP. In this study, we tested CF10 for potency advantages relative to 5-FU and trifluorothymidine (TFT, the FP component of TAS-102) and confirmed a general potency advantage for CF10 in CRC cell lines in the Broad Institute PRISM screen. We demonstrated that this potency advantage is retained in CRC cells cultured with human-like folate levels and is enhanced by LV co-treatment to a similar extent as that by 5-FU. Our results confirm CF10 development proceeding as a CF10/LV combination. Mechanistically, CF10 cytotoxicity closely correlates with poisons of DNA topoisomerase 1 (Top1) in the PRISM screen relative to 5-FU and TFT. Conclusions: Our pre-clinical data support an early-phase clinical trial for CF10 for treating liver-metastatic CRC. Full article

Background: Enterotoxigenic Bacteroides fragilis (ETBF) carries the bft toxin gene, which influences the host immune response and inflammatory pathways and promotes colorectal cancer (CRC). This study investigated the potential role of ETBF in CRC liver metastasis. Methods: We reviewed the records of 226 consecutive patients who underwent curative-intent (R0) resection of CRC liver metastases. ETBF DNA in fresh-frozen metastasis specimens was quantified using droplet digital PCR (ddPCR). Patients were grouped into very-low (≤80%; N = 178), low (80–90%; N = 24), and high (>90%; N = 24) ETBF-DNA groups. Three tissue cores per specimen were stained for CD8, CD4, CD20, FOXP3, CD68, and CD163, and immune-cell densities were measured digitally (cells/mm²). Results: ETBF DNA was detected in 219 of 226 lesions (96.9%). The densities of cytotoxic CD8⁺ T-cells, effector CD4⁺ T-cells, CD20⁺ B-cells, and CD163⁺ macrophages did not differ significantly by ETBF-DNA group (P_trend all > 0.12). FOXP3⁺ regulatory T-cells (Tregs) decreased (P_trend = 0.010), and CD68⁺ macrophages increased (P_trend = 0.020) as ETBF-DNA levels increased. ETBF-DNA levels in CRC liver metastases were not associated with disease-free survival or overall survival or serum C-reactive protein levels. Conclusions: ETBF was present in almost all CRC liver metastases. Higher ETBF levels were associated with a tumor-immune microenvironment enriched in CD68⁺ macrophages and deficient in FOXP3⁺ Tregs, suggesting that ETBF facilitates immune evasion without loss of effector lymphocytes. Although ETBF-DNA levels did not predict survival in this single-center cohort, the potential role of ETBF in immune remodeling and as a candidate biomarker and therapeutic target in metastatic CRC warrants further study. Full article

Gastrointestinal (GI) cancers, particularly colorectal and gastric cancers, majorly contribute to global cancer mortality due to frequent late-stage diagnosis and poor therapeutic response in advanced disease. Earlier detection of GI cancers is needed for a better prognosis. This review examines both traditional and emerging biomarkers that contribute significantly to early detection, prognostication, and prediction of therapeutic resistance or sensitivity. Specifically, we highlight the diagnostic utility of non-invasive liquid biopsy biomarkers such as circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomes. Moreover, we discuss the prognostic and predictive value of conventional genetic alterations, including KRAS, BRAF, and HER2. Although new findings have shown the advantages of liquid biopsy over colonoscopy, there are still limitations to the technique, such as cost-effectiveness, technological gaps in low-resource settings, and uncertain detection rates. Further studies are required to test the validity and accessibility of liquid biopsy and its biomarkers in order to advance personalized diagnosis and treatments for GI cancers. Such a study will be helpful for clinicians to better manage patients with GI cancers. Full article

Introduction: Colorectal cancer (CRC) is the third most frequent malignancy and the second cause of cancer-related death worldwide. CRC is characterized by morphologic and biological heterogeneity, and molecular profiling is required to select appropriate treatment in the metastatic setting. Mutations in KRAS are detected in approximately 40% of CRCs, with prognostic and predictive value, and with the most frequent being p.G12D. Nonetheless, there are few data on the morphologic features in KRAS-mutated CRCs. Materials and Methods: We retrospectively collected clinicopathological features and molecular profiles of CRCs in a multicenter cohort. Results: A total of 2816 patients from 12 centers were included. KRAS mutation was found in 47.4% of cases; Gly12Asp was detected in 23.9%, with different mutation frequencies between centers. Clinicohistological features associated with Gly12Asp mutation included younger patient age (≤70 years of age), higher prevalence in males (58.6%), NOS histotype (87.1%), low pathologic grade (73.9%), high grade budding—Bd3 (43.8%), and tumoral lympho-vascular invasion (68.9%). Conclusions: Recent data have pinpointed the prognostic and predictive value of Gly12Asp mutation, and our results contribute to understanding its biology, with particular focus on peculiar clinicopathological features. Moreover, we found significant differences in pathology reports and assays for molecular profiling in different centers, which can affect a standardized therapeutic approach in CRC. Full article

Background/Objectives: Colorectal cancer (CRC) frequently metastasizes to the peritoneum, significantly worsening patient prognosis. While serum tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are routinely measured, their diagnostic or prognostic role in peritoneal fluid remains unclear. This study aimed to assess the relationship between CEA and CA 19-9 levels in both serum and peritoneal fluid, and the clinical stage of CRC, particularly focusing on the presence of peritoneal metastases and positive cytology. Methods: We retrospectively analyzed data from 89 patients with histologically confirmed CRC who underwent surgery between 2020 and 2023. All patients had preoperative assessment of CEA and CA 19-9 levels in serum and peritoneal fluid, along with cytological examination of peritoneal fluid samples. Patients were categorized based on the presence or absence of macroscopic peritoneal metastases and cytology results. Results: Elevated levels of CEA and CA 19-9 in peritoneal fluid were significantly associated with the presence of peritoneal metastases. A positive cytological finding also correlated with higher marker concentrations. Conclusions: CEA and CA 19-9 levels in peritoneal fluid strongly correlate with peritoneal dissemination in CRC. These markers may serve as additional predictive factors, aiding in early detection of peritoneal spread and improved risk stratification. Their assessment may be useful in guiding intraoperative and postoperative decision-making. Full article

Colorectal cancer (CRC) stands as one of the most prevalent and lethal forms of cancer worldwide with early detection playing a crucial role in improving the survival rate. Salivary biomarkers have emerged as a promising non-invasive alternative for CRC early detection. A comprehensive search of the Web of Science, Scopus, and PubMed databases was performed to identify relevant studies published between 2018 and April 2025. Inclusion criteria focused on studies analyzing salivary biomarkers in adult CRC patients, while pediatric studies, non-diagnostic applications, and studies with insufficient statistical power were excluded. A total of 12 studies were included in this review, identifying various salivary biomarkers associated with CRC. Salivary microbiota, including Fusobacterium nucleatum and other bacterial species, demonstrated potential as diagnostic markers. Metabolomic profiling revealed elevated levels of lactate and pyruvate, reflecting metabolic alterations in CRC. Several microRNAs, such as miR-92a and miR-29a, exhibited high sensitivity and specificity for CRC detection. Additionally, protein-based biomarkers, including chemerin and sHLA-G, were found to be significantly elevated in CRC patients. Salivary biomarkers show great promise as a non-invasive, cost-effective approach for CRC detection and prognosis. Their ability to reflect systemic disease processes makes them a valuable complement to existing screening methods. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite significant advances in screening and treatment, the prognosis for advanced-stage disease continues to be poor. One thriving area of research focuses on the use of epigenetic alterations for the diagnosis, prediction of treatment response, and prognosis of CRC. In this study, we evaluated original studies and meta-analyses published within the past five years to identify the most clinically relevant epigenetic biomarkers. DNA methylation-based assays, particularly those targeting SDC2 and SEPT9 in stool and plasma, exhibit superior diagnostic accuracy compared to other epigenetic modalities. Circulating microRNAs (miRNAs), including miR-211, miR-197, and miR-21, as well as specific long non-coding RNAs (lncRNAs) such as SNHG14, LINC01485, and ASB16-AS1, also show promising diagnostic potential. Furthermore, panels combining multiple epigenetic markers, especially those incorporating DNA methylation targets, have demonstrated improved sensitivity and specificity for early-stage CRC detection. In the context of therapeutic prediction, microRNAs such as miR-140, miR-21, and miR-4442 have been associated with chemotherapy resistance and recurrence risk. DNA methylation markers like LINE-1, mSEPT9 and ERCC1 have also shown predictive value, while lncRNAs including MALAT1 and GAS6-AS1 remain less validated. Regarding prognosis, miRNAs appear to be the most promising biomarkers, with miR-675-5p and miR-150 being associated with poor survival, while miR-767-5p and miR-215 predict favorable outcomes. Methylation of NKX6.1, IGFBP3, and LMX1A has been identified as an independent negative prognostic factor, while SFRP2 hypermethylation is linked to better prognosis. Selected lncRNAs, including THOR and LINC01094, have also demonstrated significant prognostic value. Despite these advances, challenges persist, including inconsistent reporting, limited external validation, and a lack of replication by independent research groups. Full article