Colorectal cancer (CRC), the third most common cancer globally, is linked to gut microbiota imbalances. This study explores the association between gut microbiota composition and CRC, focusing on the therapeutic potential of probiotic-derived cell-free supernatants (CFSs). 50 participants, including 25 CRC patients and 25 healthy controls, were recruited and assessed for the relative abundance of six targeted gut bacterial species, including three probiotic strains (Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, and Bifidobacteriumbreve) and three non-probiotic bacteria (Enterococcus faecalis, Streptococcus bovis, and Porphyromonas gingivalis), using absolute quantification real-time PCR (qRT-PCR). Additionally, the in vitro studies investigated the anti-inflammatory effects of CFSs extracted from cultured L. acidophilus, L. rhamnosus, and B. breve, both individually and as a combined cocktail. The results showed that CRC patients exhibited significant increases in non-probiotic bacteria alongside reductions in the beneficial probiotics. Moreover, while the CFSs from all three probiotics exhibited anti-inflammatory properties, the combined CFS cocktail demonstrated the most pronounced effect, significantly downregulating pro-inflammatory cytokines IL-6 and TNF-α in HT-29 colon epithelial cells. These findings emphasize microbial imbalances as potential biomarkers for early CRC detection and underscore the therapeutic promise of probiotic-derived CFSs, presenting innovative, non-invasive strategies for managing CRC-associated inflammation.

Colorectal cancer (CRC) shows a limited response to programmed death-ligand 1 (PD-L1) immunotherapies. Akkermansia muciniphila (AKK) may enhance tumor immunity. This study examines how its Outer Membrane Vesicles (OMVs) and Amuc_1434 influence PD-L1 expression and CD8+ T cell activity in CRC. OMVs were isolated and their characteristics were examined through transmission electron microscopy and Western blotting. PD-L1 expression was quantified via Western blot, while CD8+ T cell proliferation was measured using flow cytometry. Cytokine production (interferon-gamma (IFN-γ) and interleukin-2 (IL-2)) was evaluated using ELISA. A CRC mouse model was employed to examine its impact on tumor growth and immune cell infiltration. In CRC cells, treatment with AKK-derived OMVs (AKK-OMVs) significantly downregulated PD-L1 expression (p < 0.05) and markedly increased CD8+ T cell proliferation and the levels of IFN-γ and IL-2 (p < 0.01). Amuc_1434 was identified as the key protein mediating these effects. In vivo, AKK-OMVs treatment substantially reduced tumor volume (p < 0.01) and significantly enhanced CD8+ T cell infiltration into the tumor microenvironment (p < 0.01). Additionally, AKK-OMVs-treated mice showed increased expression of immune activation markers within the tumor tissue, further indicating enhanced antitumor immunity. This study reveals that AKK-OMVs, particularly those containing Amuc_1434, can modulate PD-L1 expression and potentiate CD8+ T cell-mediated antitumor immunity in CRC. These findings suggest a novel approach to overcoming resistance to immune checkpoint inhibitors in CRC.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Increasing evidence suggests that alterations in the immune system may play a pivotal role in the initiation and progression of CRC. However, the precise causal relationship between specific immune cell phenotypes and CRC remains incompletely understood. Elucidating this connection may unveil novel therapeutic targets for the treatment of CRC.

To explore the causal relationship between immune cell phenotypes and CRC, we conducted a comprehensive bidirectional Mendelian randomization (MR) analysis. Genetic variants were utilized as instrumental variables (IVs), with the inverse variance weighting (IVW) method employed to assess the effect of specific immune cell phenotypes on CRC risk. Sensitivity analysis were performed to evaluate the robustness of our findings, while heterogeneity analysis were conducted to minimize the potential impact of pleiotropy.

Our MR analysis revealed potential causal associations between various immune phenotypes and CRC. Specifically, 34 immune cell types were found to be potentially causally associated with colon cancer, while 29 immune cell types showed a potential causal relationship with rectal cancer. Sensitivity analysis further confirmed the robustness of these associations, suggesting that these immune cell phenotypes may play a significant role in the development of CRC.

Our study provides evidence for a causal relationship between immune cell phenotypes and CRC. These findings suggest that immune cell characteristics may serve as potential biomarkers for CRC and could represent novel therapeutic targets. However, further experimental research is needed to explore the underlying mechanisms in greater detail and to validate the clinical applicability of these findings.

Colorectal cancer (CRC) is one of the most prominent cancers globally, with its incidence rising among younger adults due to improved screening practices. However, existing algorithms for CRC prediction are frequently trained on datasets that primarily reflect older persons, thus limiting their usefulness in more diverse populations. Additionally, the part of nutrition in CRC deterrence and management is gaining significant attention, although computational approaches to analyzing the impact of diet on CRC remain underdeveloped. This research introduces the Nutritional Impact on CRC Prediction Framework (NICRP-Framework), which combines Natural Language Processing (NLP) techniques with Adaptive Tunicate Swarm Optimized Large Language Models (ATSO-LLMs) to present important insights into the part of the diet in CRC care across diverse populations. The colorectal cancer dietary and lifestyle dataset, encompassing >1000 participants, is collected from multiple regions and sources. The dataset includes structured and unstructured data, including textual descriptions of food ingredients. These descriptions are processed using standardization techniques, such as stop word removal, lowercasing, and punctuation elimination. Relevant terms are then extracted and visualized in a word cloud. The dataset also contained an imbalanced binary CRC outcome, which is rebalanced utilizing the random oversampling. ATSO-LLMs are employed to analyze the processed dietary data, identifying key nutritional factors and forecasting CRC and non-CRC phenotypes based on dietary patterns. The results show that combining NLP-derived features with ATSO-LLMs significantly enhances prediction accuracy (98.4 %), sensitivity (97.6 %) specificity (96.9 %) and F1-Score (96.2 %), with minimal misclassification rates. This framework represents a transformative advancement in life science by offering a new, data-driven approach to understanding the nutritional determinants of CRC, empowering healthcare professionals to make more precise predictions and adapted dietary interventions for diverse populations.

Colorectal cancer (CRC), as a highly prevalent malignant tumor globally, faces the dual challenges of drug resistance of cancer stem cells and immune escape in its treatment. Although the traditional Chinese medicine Yigong San (YGS) shows potential in improving the clinical adverse reactions of CRC, its core active components and mechanism of action remain unclear. Based on network pharmacology screening, this study for the first time discovered that Gomisin B might regulate the progression of CRC through the Toll-like receptor 4/Nuclear Factor-kappa B (TLR4/NF-κB) signaling pathway, and aimed to systematically reveal the molecular mechanisms by which YGS and Gomisin B inhibited the malignant phenotypes and immune escape of CRC cells.

The The Cancer Genome Atlas (TCGA) database was integrated with network pharmacology analysis to screen for the key target of CRC, Gomisin B, and its associated TLR4/NF-κB pathway. Through in vitro CRC stem cell models and mouse xenograft tumor models, techniques such as CCK-8, Transwell, flow cytometry, qPCR/WB were used to evaluate the effects of YGS and Gomisin B on proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT), and to detect the expression of TLR4 and downstream inflammatory factors.

Both YGS and Gomisin B inhibited the proliferation, migration and invasion of CRC stem cells and tumor tissues. Meanwhile, they promoted apoptosis but reduced the expression of the inflammatory factor TLR4 and proteins associated with the NF-κB pathway, thereby exerting suppressive effects on tumorigenesis and disease progression. YGS might also impede EMT progression through modulation of the NF-κB pathway.

This study for the first time elucidated the dual anti-tumor mechanisms of YGS, which sensitized CRC stem cells and inhibited immune escape by targeting the TLR4/NF-κB pathway through Gomisin B. It provides a pharmacological basis for the modern research of traditional Chinese medicine compound against CRC.

Not applicable.

The increased demand for markers for colorectal cancer (CRC) highlights the importance of investigating immune cells involved in CRC progression. This study aims to dissect the mast cells in CRC, characterize the role of mast cells in CRC development, coordinate molecular communication between mast cells and malignant cells, and construct and validate a prognostic classification model based on mast cell markers.

Single-cell transcriptome data of CRC patients were extracted from GSE146771 for cell classification and annotation. The malignant cells were identified by copykat and the communication between mast cells and malignant cells was analyzed by CellChat. Least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression analysis of mast cell markers were performed in the TCGA-COAD cohort to construct a prognostic classification model. qRT-PCR was performed to detect the mRNA expression of the molecules in the classification model in P815 and MC-9 cells. The co-culture experiment of MC38 and P815 cells were performed in 12-well transwell dish. Wound healing assay and Transwell assay were performed to detect cell migration and invasion.

10,186 high-quality cells in GSE146771 were annotated to 9 cell types. Six markers in mast cells (HDC, GATA2, ASAH1, BTBD19, TIMP1, FAM110A) were selected to construct a classification model. The high-risk score defined showed high infiltration of immunosuppressive cells, including endothelial cells, CAFs, Tregs and high angiogenesis and epithelial-mesenchymal transition (EMT) activities. In the model, HDC were abnormally low expressed in P815 cells, while BTBD19, FAM110A, GATA2, ASAH1 and TIMP1 showed excessive expression in P815 cells. Knockdown of GATA2 in the co-culture system of P815 and MC38 cells blocked cell migration and invasion.

This study identified the cell types within CRC, elaborated the cellular functions of mast cells in CRC development and their molecular communication to coordinate malignant cells, and highlighted the molecular components and biological features that constitute promising prognostic classification model.

Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies, necessitating the study of cellular and molecular changes within the tumor microenvironment. While pathological image analysis remains the gold standard, its labor-intensive nature limits its broad application. This study proposes a label-free CRC typing approach using intelligent optical time-stretch (OTS) imaging flow cytometry combined with multi-instance learning. Specifically, we construct a high-throughput cell image acquisition system by integrating OTS imaging with microfluidic cell focusing, capturing 363 931 cell images from 10 clinical samples. To address cell diversity and heterogeneity, we employ a multi-instance learning framework, which incorporates a multi-level attention mechanism to explore feature interactions at both channel and instance levels. Finally, we apply a majority voting mechanism to enable efficient label-free CRC typing. Our method achieves an accuracy of 85.78% in distinguishing normal and cancerous cells, while encouraging CRC typing performance across all 10 clinical samples.

Early diagnosis of colorectal cancer (CRC), a malignant tumor with high incidence and mortality rates worldwide, can significantly reduce both its incidence and mortality. Among cancer diagnostic methods, tumor fluorescence imaging provides a non-invasive approach, eliminating the need for tissue biopsy and minimizing patient discomfort. In this study, we identified a water-soluble quinolinium molecular fluorescent probe (CYI), which exhibits a dose-dependent quantum yield in PBS solution, reaching 5.96% at a concentration of 20 µM. The results demonstrated that CYI selectively enters CRC cells and maintains stable fluorescence intensity within them by specifically targeting the mitochondria and lysosomes, leading to probe accumulation and enhanced intracellular fluorescence. Importantly, toxicity assays at both the cellular and animal levels confirmed that CYI is highly biocompatible at fluorescence imaging doses, with no toxic effects observed in normal colorectal cells or organisms. This study identifies CYI as a water-soluble molecular fluorescent probe with a high biosafety profile, excellent imaging stability, and preferential uptake by CRC cells, demonstrating strong potential for early CRC screening and in vivo monitoring.

Aims/Background Colorectal cancer (CRC) is one of the major global health problems, with high morbidity and mortality, underscoring the need for new diagnostic and prognostic tools. Therefore, this study aims to evaluate the significance of integrating radiomics with genetic data in CRC prognostic assessment and improve the accuracy of prognosis prediction. Methods This study included computed tomography (CT) images from 225 CRC patients and RNA-seq information from 654 patients, obtained from the TICA database. Key radiomics features and genes were identified through radiomics feature extraction, least absolute shrinkage and selection operator (LASSO) regression analysis, and Kaplan-Meier survival analysis. Furthermore, a CRC prognostic model was constructed using these key genes and radiomics features. Results This study identified 170 key radiomics features. Out of them, five were significantly associated with CRC prognosis. Transcriptome data analysis identified 8 key genes, among which the high expressions of Inhibin Subunit Beta B (INHBB), Potassium Voltage-Gated Channel Subfamily Q Member 2 (KCNQ2), and Ubiquilin Like (UBQLNL) were significantly correlated with poor prognosis. Age, tumor stage, pathological T stage, and pathological N stage were determined as independent prognostic factors. Moreover, immune infiltration analysis demonstrated that the immune score of the low-risk group was higher than that of the high-risk group, with significant differences in some immune cells, and key genes were correlated with immune cells. Additionally, the constructed CRC prognostic model incorporating three genes, INHBB, KCNQ2, and UBQLNL, exhibited high prediction accuracy in the validation set, with area under the curve (AUC) values of 0.80, 0.87, and 0.84 at 1-year, 3-year, and 5-year, respectively, indicating good prediction performance and reliability of the model. Conclusion The multimodal data combining radiomics features and gene expression data can improve the accuracy of CRC prognostic assessment, providing a valuable prognostic prediction tool for clinical practice and helping to guide the selection and optimization of treatment regimens.

Colorectal cancer (CRC) is a prevalent malignant tumor characterized by a high mortality rate, with significant challenges persisting in the identification and management of its metastatic stage. The role of checkpoint kinase 1 (CHEK1), a cell cycle checkpoint kinase, in CRC has not been fully clarified. We hypothesize that the upregulation of CHEK1 may enhance the proliferation of CRC cells, indicating its potential as a novel therapeutic target for CRC therapy.

To investigate the expression and function of CHEK1 in CRC, this study utilizes single-cell RNA sequencing and tissue microarray data.

Single-cell RNA sequencing technology was employed to analyze CRC cells from the GSE144735 dataset, and immunohistochemistry was conducted to confirm the expression of CHEK1 in CRC and adjacent tissues. We also integrated mRNA expression data from multiple public databases to assess global CHEK1 expression in CRC. Molecular docking experiments were performed to explore the interaction between CHEK1 and the potential drug nitidine chloride (NC), as well as to investigate the influence of CHEK1 on CRC cell proliferation.

We found comparatively elevated CHEK1 expression in the malignant epithelial cells of CRC, with marked upregulation of its mRNA levels in CRC tissues. Immunohistochemical analysis further confirmed the high expression of CHEK1 in CRC tissues, and the receiver operating characteristic curve demonstrated high accuracy (area under the curve = 0.964) for CHEK1 as a biomarker. Analysis of global datasets indicated a statistically significant overexpression of CHEK1 in CRC (standard mean difference = 1.81, P < 0.01), with summary receiver operating characteristic analysis yielding sensitivity and specificity values of 0.83 and 0.88, respectively. Molecular docking studies indicated that NC specifically targeted CHEK1, while clustered regularly interspaced short palindromic repeats knockout experiments demonstrated that CHEK1 promoted CRC cell proliferation.

Upregulation of CHEK1 promotes CRC cell proliferation. However, the dataset's diversity is limited, requiring further investigation into its specific mechanisms.

Background: This study aims to objectively evaluate the overall quality of colonoscopies using a specially trained deep learning-based semantic segmentation neural network. This represents a modern and valuable approach for the analysis of colonoscopy frames. Methods: We collected thousands of colonoscopy frames extracted from a set of video colonoscopy files. A color-based image processing method was used to extract color features from specific regions of each colonoscopy frame, namely, the intestinal mucosa, residues, artifacts, and lumen. With these features, we automatically annotated all the colonoscopy frames and then selected the best of them to train a semantic segmentation network. This trained network was used to classify the four region types in a different set of test colonoscopy frames and extract pixel statistics that are relevant to quality evaluation. The test colonoscopies were also evaluated by colonoscopy experts using the Boston scale. Results: The deep learning semantic segmentation method obtained good results, in terms of classifying the four key regions in colonoscopy frames, and produced pixel statistics that are efficient in terms of objective quality assessment. The Spearman correlation results were as follows: BBPS vs. pixel scores: 0.69; BBPS vs. mucosa pixel percentage: 0.63; BBPS vs. residue pixel percentage: -0.47; BBPS vs. Artifact Pixel Percentage: -0.65. The agreement analysis using Cohen's Kappa yielded a value of 0.28. The colonoscopy evaluation based on the extracted pixel statistics showed a fair level of compatibility with the experts' evaluations. Conclusions: Our proposed deep learning semantic segmentation approach is shown to be a promising tool for evaluating the overall quality of colonoscopies and goes beyond the Boston Bowel Preparation Scale in terms of assessing colonoscopy quality. In particular, while the Boston scale focuses solely on the amount of residual content, our method can identify and quantify the percentage of colonic mucosa, residues, and artifacts, providing a more comprehensive and objective evaluation.

Rose Bengal (RB) is a promising photosensitizer (PS) for photodynamic therapy (PDT), but its application to colorectal carcinoma remains largely unexplored. Herein, we employ in vitro assays to demonstrate that incorporation of RB has substantial phototoxicity against Caco-2 cells, with more than 80% reduction in cell viability for 24 h incubation with 5 × 10-6 mol/L RB followed by irradiation. In contrast, RB had minimal toxicity without irradiation. The mechanisms of RB action were further elucidated using confocal fluorescence microscopy, Langmuir monolayers as cell membrane models, and flow cytometry to determine the cell death pathways. Flow cytometry revealed that the primary mode of cell death was late apoptosis. RB incorporation affected Caco-2 plasma membrane morphology under light irradiation, and membrane interactions were confirmed using Langmuir monolayers of Caco-2 lipid extracts. Incorporation of RB into the monolayers shifted the pressure-area isotherms toward larger molecular areas, especially at low surface pressures and increasing RB concentrations (1, 10, and 25 × 10-6 mol/L). RB adsorption also caused a decrease in the in-plane elasticity (Cs1-) of the Caco-2 monolayers, with a large increase in monolayer flexibility as RB concentration increased. According to polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), the anionic RB interacted electrostatically with positively charged phospholipid groups. Moreover, the changes in surface area observed in the monolayers upon RB incorporation and irradiation could be attributed to hydroperoxidation reactions triggered by the generation of singlet oxygen (1O2). These findings indicate that RB may be used as a PS in the PDT of colorectal cancer, providing detailed insights into its mechanism of action and phototoxicity.

Colorectal cancer (CRC) is a prevalent malignancy worldwide, often treated with chemotherapy despite its limitations, including adverse effects and resistance. The traditional Chinese medicine (TCM) Jianpi formula has been demonstrated to improve efficacy of chemotherapy, however the underlying mechanisms still need to be explored. In this study, we aim to screen bioactive peptides derived from the blood of CRC patients through peptidomics and explore the molecular mechanisms of the candidate peptides in the inhibition of CRC using multi-omics analysis.

In this study, we recruited 10 patients with CRC who had received either adjuvant chemotherapy or adjuvant chemotherapy combined with the traditional Chinese medicine Jianpi formula after surgery. We collected plasma samples at 2 cycles of adjuvant therapy and performed peptidomic analysis on these samples. The differentially bioactive peptides were screened using a model of HCT116 cells in vitro. To investigate the molecular mechanism underlying YG-22's inhibition of the colorectal cancer cell line HCT116, we performed a multi-omics analysis, including transcriptome, metabolome, chromatin accessibility, H3K4Me3 histone methylation, and NF-κB binding site analyses.

Differential peptides were identified in plasma samples from patients treated with adjuvant chemotherapy combined with the Jianpi formula. Among these peptides, YG-22 exhibited the strongest cytotoxic effect on HCT116 cells, reducing cell viability in a dose- and time-dependent manner. Transcriptome analysis highlighted that YG-22 treatment in CRC modulates key pathways associated with lysosome-mediated degradation and apoptosis. Metabolomic profiling further indicated disruptions in tumor-supportive metabolic pathways. Chromatin accessibility and histone modification analyses suggested that YG-22 induces epigenetic reprogramming. Additionally, treatment with YG-22 resulted in significant changes in NF-κB binding and pathway activation.

This study demonstrates that combining chemotherapy with TCM Jianpi formula enriches the molecular landscape and generates bioactive peptides with strong antitumor activity. Furthermore, this study also lays the foundation for further development of peptide-based therapies and highlights the value of combining traditional and modern therapeutic strategies for CRC management.

Despite the proven effectiveness of colorectal cancer (CRC) screening in reducing mortality, adherence rates for fecal occult blood testing (FOBT) and colonoscopy remain low among Turkish adults. This study aimed to assess the stages of adoption of CRC screening behaviors, identify the factors influencing adoption, and examine the perceived benefits and barriers to screening.

A cross-sectional study was conducted in Istanbul's Anatolian region from May to June 2022, involving 498 adults aged 50-70 years. Multistage cluster sampling was used to select 20 primary healthcare centers. A structured questionnaire was administered to assess sociodemographic characteristics, health perceptions, knowledge of colorectal cancer (CRC) screening, and readiness for screening based on the transtheoretical model. The benefits and barriers to screening were evaluated using the Turkish version of "The Instruments to Measure CRC Screening Benefits and Barriers."

The participants (mean age: 59.10 ± 5.71 years) showed greater recognition of colonoscopy (68.7%) than FOBT (39.8%). Most participants were in the precontemplation stage for FOBT (58.6%) and colonoscopy (63.9%). Perceptions of benefits were associated with education, employment, income, health status, familial CRC history, and screening knowledge (p < 0.05). Perceived barriers were linked to lack of knowledge and provider recommendations (p < 0.05). The participants in the precontemplation stage reported fewer benefits and more barriers compared to those in advanced stages (p < 0.05).

Colonoscopy is more widely recognized than FOBT among the Turkish adult population; however, a significant proportion remains in the precontemplation stage for screening. Perceptions of benefits and barriers are influenced by sociodemographic factors, health status, and CRC knowledge. Interventions addressing these barriers and raising awareness could improve CRC screening uptake and help reduce the disease burden.

Interferon-Induced Protein with Tetratricopeptide Repeats 3 (IFIT3) plays a dual role in innate immunity and tumor immunity, functioning as both a viral defense molecule and a regulator of tumor progression. This review explores the mechanisms through which IFIT3 modulates immune responses, including interferon signaling, RIG-I-like receptors, and the NF-κB pathway. IFIT3 facilitates immune evasion and promotes inflammation-mediated tumor growth by regulating immune checkpoints and the tumor microenvironment, its emerging role as a target for cancer immunotherapy opens new avenues for therapeutic strategies. Finally, this paper underscores IFIT3's potential clinical applications in the modulation of tumor immunity, highlighting the need for further research on IFIT3-targeted therapies.

Colorectal cancer (CRC) is a serious threat to human health with the third morbidity and the second cancer-related mortality worldwide. It is urgent to explore more effective strategy for CRC because of the acquired treatment resistance from the non-surgical conventional therapies, including radiation, chemotherapy, targeted therapy and immunotherapy. Ferroptosis is a novel form of programmed cell death characterized by iron-dependent lipid peroxidation species (ROS) accumulation and has been identified as a promising target for cancer treatment, especially for those with treatment resistance. In this review, we mainly summarize the recent studies on the influence and regulation of ferroptosis by which (including gut microbiota) modulating the metabolism of iron, amino acid and lipid. Thus this analysis may provide potential targets for inducing CRC ferroptosis and shed lights on the future application of ferroptosis in CRC.

Colorectal cancer, ranking second place in global cancer mortality, arises from diverse causes. There is growing recognition of the substantial involvement of the epigenetic modifications of histones at the DNA level in the occurrence of CRC.

To assess the expression of p53, HDAC1, and HDAC3 proteins in a cohort of CRC patients and to analyze potential relationship between their expression and the stages of CRC progression.

The retrospective investigation was carried out on 95 paraffin-embedded CRC tissue samples. The expression of p53, HDAC1, and HDAC3 was assessed immunohistochemically.

Notably, the expression of the p53 protein in CRC tissue samples exhibited a prominent correlation with the protein expression of both HDAC1 (p < 0.001, rho = 0.522) and HDAC3 (p < 0.001, rho = 0.411), as well as the advanced TNM staging of CRC (p = 0.002, rho = 0.313). Downregulation of p53 was correlated with underexpressed HDAC1 and HDAC3. Nevertheless, the observed expression of p53 exhibited a significant negative correlation with the age of the patients.

The data on HDACs-p53 co-expression suggest a possible mechanism of interaction between the expression of these proteins.

Colorectal cancer (CRC), characterized by its complex genetic heterogeneity and varied responses to treatment, is a leading cause of cancer-related mortality worldwide. The role of N1-methyladenosine (m1A)-related genes in tumor biology remains underexplored. This study aimed to investigate the prognostic value of m1A-related genes in CRC, characterize their role in tumor molecular subtyping, and explore their influence on the tumor microenvironment (TME) and immune infiltration.

To identify prognostic markers, univariate Cox analysis was performed using multiple datasets, including TCGA and GEO, identifying 43 m1A-related genes. Four distinct molecular subtypes of CRC were defined based on the expression of these genes using non-negative matrix factorization (NMF). Immune infiltration analysis was conducted, and the TIDE algorithm was used to predict response to immune checkpoint inhibitors (ICIs). Furthermore, a prognostic model based on m1A-related genes was constructed and validated across multiple datasets.

The results demonstrated that the four CRC molecular subtypes exhibited significant differences in survival outcomes and clinical characteristics. Stromal cells showed higher m1A scores, suggesting a regulatory role in the TME. There was a positive correlation between m1A-related gene expression and immune checkpoint genes. Moreover, the constructed prognostic model showed robust predictive performance and outperformed other recently published models.

The findings suggest that m1A-related genes are not only valuable biomarkers for CRC prognosis but also have significant implications for the immune landscape and could serve as potential targets for therapeutic intervention, particularly in the context of immunotherapy. For instance, SLC12A2 was found to enhance invasion, proliferation, and migration of colorectal cancer cells while inhibiting apoptosis. Further studies are needed to understand the functional roles of m1A modifications across different cell types within the TME.

Colorectal cancer (CRC) is the third most frequently diagnosed malignancy worldwide. Currently, irinotecan (CPT-11) is used alone or in combination with other drugs to treat patients with advanced CRC. However, the 5-year survival rate for metastatic CRC remains below 10 %, largely due to chemotherapy resistance. Several genes, including ABCG2, CYP3A4, MCL1, and MLH1 contribute to irinotecan resistance. This study aimed to identify microRNAs that simultaneously regulate the expression of these genes in irinotecan-resistant cell lines and study their effect on resistant colorectal cancer cells.

Irinotecan-resistant colorectal cancer cell lines were developed by intermittently exposing HCT116 and SW480 cell lines to gradually increasing doses of irinotecan over four generations. These resistant cell lines were designated HCT116-R1, HCT116-R2, HCT116-R3, HCT116-R4 and SW480-R1, SW480-R2, SW480-R3, SW480-R4. The induction of resistance was confirmed using MTT assays, by calculating IC50 values for each generation and comparing them to the parental cells. The expression levels of the ABCG2, CYP3A4, MCL1, and MLH1 genes, along with miR-3664-3p, were initially measured in all resistant and parental cell lines using quantitative real-time PCR. Following transfection of HCT116-R3 and SW480-R3 cells with pre-miR-3664-3p, the expression levels of ABCG2, CYP3A4, MCL1, MLH1, and miR-3664-3p were re-evaluated using real-time PCR.

In resistant cell lines derived from HCT116 and SW480, increased expression of the ABCG2, CYP3A4, and MCL1 genes was observed. However, a reduction in CYP3A4 expression was noted in the final resistant lines from both cell lines. Additionally, while MLH1 expression increased in HCT116-derived cell lines, no significant increase was observed in SW480-derived lines. A consistent decrease in miR-3664-3p expression was found across all resistant cell lines. When we transfected HCT116-R3 and SW480-R3 cells with pre-miR-3664-3p, there was an increase in miR-3664-3p expression and a reduction in ABCG2, CYP3A4, MCL1, and MLH1 gene expression. This led to increased sensitivity to irinotecan.

It can be concluded that miR-3664-3p can be considered a regulator of resistance to irinotecan by modulating the expression of ABCG2, CYP3A4, MCL1, and MLH1 genes.

To explore the risk factors for cardiotoxicity in patients with gastrointestinal (GI) tumors treated with fluorouracil drugs.

This study included patients with GI tumors who received fluorouracil at our hospital between January 2018 and April 2022. The demographic and clinical characteristics were collected. The risk factors associated with the cardiotoxicity of fluorouracil were explored using multivariable logistic regression.

A total of 300 patients were finally included and divided into the cardiotoxicity (n = 81) and non-cardiotoxicity groups (n = 219). The occurrence of fluorouracil-induced cardiotoxicity was higher in patients with hypertension, hyperlipidemia, diabetes mellitus, older age, those treated with capecitabine, and combined radiotherapy. The multivariable logistic regression showed that treatment with capecitabine, history of hyperlipidemia, history of diabetes, older age, and combined radiotherapy were independent risk factors for the cardiotoxicity of fluorouracil.

Hyperlipidemia, diabetes, older age, treatment with capecitabine, and adjuvant radiotherapy might be independent risk factors for the cardiotoxicity of fluorouracil in patients with GI tumors.

(1) Background: Colorectal cancer is one of the leading causes of cancer-related death, while early detection decreases incidence and mortality. Current screening programs involving fecal immunological testing and colonoscopy commonly bring about unnecessary colonoscopies, which adds burden to healthcare systems. The objective of this study was to provide an assessment of the diagnostic performance of an electronic nose serving as a complementary screening tool to improve current screening programs in clinical settings. (2) Methods: We conducted a case-control study that included patients from a medical center with colorectal cancer and non-colorectal cancer controls. We analyzed the composition of volatile organic compounds in their exhaled breath using the electronic nose. We then used machine learning algorithms to develop predictive models and provided the estimated accuracy and reliability of the breath testing. (3) Results: We enrolled 77 patients, with 40 cases and 37 controls. The area under the curve, Kappa coefficient, sensitivity, and specificity of the selected model were 0.87 (95% CI 0.76-0.95), 0.66 (95% CI 0.49-0.83), 0.81, and 0.85. For subjects at an early stage of disease, the sensitivity and specificity were 0.90 and 0.85. Excluding smokers, the sensitivity and specificity were 0.88 and 0.92. (4) Conclusions: This study highlights the promising potential of breath testing using an electronic nose for enabling early detection and reducing unnecessary treatments. However, more independent data for external validation are required to ensure applicability and generalizability.

Several clinical studies have evaluated the relationship between copper on colorectal cancer (CRC), but the results are contradictory. This study aimed to conduct a systematic review and meta-analysis to investigate copper measured in two biological matrices (serum/plasma/blood and tissue) and dietary intake in CRC patients compared to healthy controls. We conducted a comprehensive and systematic search in PubMed, Scopus, Embase, and Web of Science. We included studies that reported copper levels in serum/plasma/blood, tissue, or from the diet, with an observational study design (cohort and case-control studies). Study quality was assessed with the Newcastle-Ottawa scale and potential causes of heterogeneity were evaluated. Standardized mean differences (SMD) with 95% confidence interval (CI) were pooled using random-effect models. Overall pooled odds ratio and 95% CI for the risk of CRC were calculated. Twenty-six studies (23 case-control and 3 cohort studies) with a total of 227 354 participants were included. Most of the studies presented low (50%) or moderate quality (42.3%). No differences in serum/plasma/blood copper levels (SMD = 0.23; 95% CI: -0.23, 0.70; I2 = 97.3%, 19 studies), tissue copper levels (SMD = -1.69; 95% CI: -3.41, 0.03; I2 = 85.6%, 2 studies), or copper/zinc ratio (SMD = 1.19; 95% CI: 0.54, 1.84; I2 = 95.3%, 6 studies) were found between CRC patients and healthy controls. Regarding dietary copper, CRC patients had a lower intake (SMD = -0.27; 95% CI: -0.51, -0.03; I2 = 0.0%, 2 studies). No differences were found in copper levels between CRC patients and healthy controls. However, evidence shows mostly low or moderate quality, and results were heterogeneous. More prospective studies with an adequate methodological approach are needed.

Aggressive biological behavior leads to unfavorable survival of colorectal cancer (CRC) patients. Dysregulation of TXNIP has been reported to be associated with the occurrence, proliferation and metastasis of malignancies such as liver cancer, lung cancer, kidney cancer, gastric cancer, and pancreatic cancer. MiR-424-5p has been reported as a negative regulator of TXNIP involved in lipopolysaccharide-induced acute kidney injury. And disordered Hippo pathway and YAP/TAZ-TEAD activity are related to tumor progression. The study was designed to clarify the function of miR-424-5p and thioredoxin interacting protein (TXNIP) in the progression of CRC.

The expression pattern of TXNIP and miR-424-5p was detected by immunohistochemistry, qRT-PCR and/or Western blotting. CCK-8 assays and transwell assays were applied to investigate the effect of TXNIP and miR-424-5p on cell proliferation, invasion and migration. Luciferase reporter assays were used to verify the transcriptional regulation among TXNIP, miR-424-5p and Hippo signaling pathway.

TXNIP was poorly expressed whereas miR-424-5p was highly expressed in CRC tissues and cells. TXNIP overexpression suppressed proliferation, invasion and migration of CRC cells. It also suppressed the malignant behavior of the CRC cells promoted by miR-424-5p. Mechanically, TXNIP overexpression significantly inhibited YAP/TAZ transcriptional activity, and the highly expressed miR-424-5p in CRC targeted TXNIP mRNA.

The study clarify a novel miR-424-5p/TXNIP/Hippo signaling pathway that facilitated CRC cells proliferation, migration and invasion. The above findings suggested that miR-424-5p and TXNIP might serve as the potential therapeutic targets for CRC patients.

Colorectal cancer (CRC) is the third most prevalent malignancy and the second leading cause of cancer-related mortality worldwide, with an increasing shift towards younger age of onset. In recent years, there has been increasing recognition of the significance of tRNA-derived small RNAs (tsRNAs), encompassing tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs). Their involvement in regulating translation, gene expression, reverse transcription, and epigenetics has gradually come to light. Emerging research has revealed dysregulation of tsRNAs in CRC, implicating their role in CRC initiation and progression, and highlighting their potential in early diagnosis, prognosis, and therapeutic strategies. Although the clinical application of tsRNAs is still in its early stages, recent findings highlight a close relationship between the biogenesis and function of tsRNAs, tRNA chemical modifications, and the tumor immune microenvironment (TIME). Additionally, similar to other small RNAs, tsRNAs can be effectively delivered via nanoparticles (NPs). Consequently, future research should focus on elucidating the clinical significance of tsRNAs concerning base modifications, TIME regulation, cancer immunotherapy, and NPs delivery systems to facilitate their clinical translation.

Cancer immunotherapy has emerged as one of the most promising modalities for cancer treatment providing hopes of cancer patients with the significant advantages over traditional antitumor therapy methods. Supramolecular assemblies based on host-guest interactions have been widely explored in the field of cancer immunotherapy as the delivery systems. A variety of supramolecular materials show unique features for efficient drug encapsulation, targeting delivery and release, which are favorable to activate antitumor immune responses especially through combination of different treatment strategies. In this review article, we summarize the research progresses of supramolecular assemblies via host-guest interactions for tumor immunotherapy. The construction of various drug delivery systems including hydrogels, liposomes, and polymeric nanoparticles, the drug encapsulation and delivery, as well as advantages and disadvantages are discussed. The perspectives related to future developments in this field are also described.

Long non-coding RNA (lncRNA) is a type of non-coding RNA distinguished by a length exceeding 200 nucleotides. Recent studies indicated that lncRNAs participate in various biological processes, such as chromatin remodeling, transcriptional and post-transcriptional regulation, and the modulation of cell proliferation, death, and differentiation, hence influencing gene expression and cellular function. ADAMTS9-AS1, an antisense long non-coding RNA situated on human chromosome 3p14.1, has garnered significant interest due to its pivotal involvement in the advancement and spread of diverse malignant tumors. ADAMTS9-AS1 functions as a competitive endogenous RNA (ceRNA) that interacts with multiple microRNAs (miRNAs) and plays a crucial role in regulating gene expression and cellular functions by modulating essential signaling pathways, including PI3K/AKT/mTOR, Wnt/β-catenin, and Ras/MAPK pathways. Dysregulation of this factor has been linked to tumor development, migration, invasion, and resistance to apoptotic mechanisms, including as iron-induced apoptosis, underscoring its intricate function in cancer pathology. While current research has clarified certain pathways involved in cancer formation, additional clinical and in vivo investigations are necessary to enhance comprehension of its specific involvement across various cancer types. This review encapsulates the recent discoveries on the correlation of ADAMTS9-AS1 with numerous malignancies, clarifying its molecular mechanisms and its prospective role as a therapeutic target in oncology. Furthermore, it identifies ADAMTS9-AS1 as a potential early diagnostic biomarker and therapeutic target, offering novel opportunities for targeted intervention in oncology.

Epidemiological studies have suggested that following long-term, low-dose daily aspirin (LTLDA) administration for more than 5 years at 75-100 mg/day, 20-30% of patients (50-80 years old) had a lower risk of developing colorectal cancer (CRC) and about the same proportion in developing iron deficiency anemia (IDA). In cases of IDA, an increase in iron excretion is suspected, which is caused by aspirin chelating metabolites (ACMs): salicylic acid, salicyluric acid, 2,5-dihydroxybenzoic acid, and 2,3-dihydroxybenzoic acid. The ACMs constitute 70% of the administered aspirin dose and have much longer half-lives than aspirin in blood and tissues. The mechanisms of cancer risk reduction in LTLDA users is likely due to the ACM's targeting of iron involved in free radical damage, iron-containing toxins, iron proteins, and associated metabolic pathways such as ferroptosis. The ACMs from non-absorbed aspirin (about 30%) may also mitigate the toxicity of heme and nitroso-heme and other iron toxins from food, which are responsible for the cause of colorectal cancer. The mode of action of aspirin as a chelating antioxidant pro-drug of the ACMs, with continuous presence in LTLDA users, increases the prospect for prophylaxis in cancer and other diseases. It is suggested that the anticancer effects of aspirin depend primarily on the iron-chelating antioxidant activity of the ACMs. The role of aspirin in cancer and other diseases is incomplete without considering its rapid biotransformation and the longer half-life of the ACMs.

Colostomy is important in the treatment of colorectal cancer. However, surgical site wound infections after colostomy seriously affect patients' physical recovery and quality of life.

To investigate the ability of high-quality nursing care to prevent surgical site wound infections and reduce post-colostomy complications in patients with colorectal cancer.

Eighty patients with colorectal cancer who underwent colostomy at our hospital between January 2023 and January 2024 were selected as research subjects. The random number table method was used to divide the participants into control and research groups (n = 40 each). The control group received routine nursing care, while the research group received high-quality nursing care. The differences in indicators were compared between groups.

The baseline characteristics did not differ between the research (n = 40) and control (n = 40) groups (P > 0.05). The incidences of wound infection, inflammation, and delayed wound healing were significantly lower in the research (5.00%) vs control (25.00%) group (P = 0.028). The incidence of postoperative complications, including fistula stenosis, fistula hemorrhage, fistula prolapse, peristome dermatitis, urinary retention, pulmonary infection, and intestinal obstruction, was significantly lower in the research (5.00%) vs control (27.50%) group (P = 0.015). In addition, the time to first exhaust (51.40 ± 2.22 vs 63.80 ± 2.66, respectively; P < 0.001), time to first bowel movement (61.30 ± 2.21 vs 71.80 ± 2.74, respectively; P < 0.001), and average hospital stay (7.94 ± 0.77 vs 10.44 ± 0.63, respectively; P < 0.001) were significantly shorter in the research vs control group. The mean Newcastle satisfaction with nursing scale score was also significantly higher in the research (91.22 ± 0.96) vs control (71.13 ± 1.52) group (P < 0.001).

High-quality nursing interventions can effectively reduce the risk of wound infections and complications in patients undergoing colostomy, promote their postoperative recovery, and improve their satisfaction with the nursing care received.

The objective of this study was to evaluate the predictive value of 18F-fluorodeoxyglucose [18F]FDG positron emission tomography (PET-CT) radiomic parameters in relation to KRAS/BRAF/EGFR mutations in patients with metastatic colorectal cancer (mCRC).

Blood samples were collected from 90 mCRC patients to assess KRAS G13V, BRAF V600E, and EGFR exon 20 mutations. [18F]FDG PET-CT scans were performed, and radiomic parameters, including the SUV max, max TBR, total MTV, and total TLG, were calculated and correlated with different genotypes and haplotypes of the aforementioned mutations.

The SUV max, TLG, and TBR were significantly greater in patients with the KRAS G13V and BRAF V600E mutations than in patients with the wild-type genotype. The SUVmax was also significantly greater in patients with EGFR exon 20 mutations. Haplotype analysis revealed that the SUVmax was significantly greater in patients with KRAS/BRAF/EGFR mutations than in other patients, with a specificity of 68.18% and sensitivity of 65.28%.

The results suggest that [18F] FDG PET-CT radiomic parameters, particularly the SUV max, have the potential to serve as noninvasive tools for predicting the KRAS/BRAF/EGFR mutation status in mCRC patients.

There is growing evidence that the protein family of Gasdermins (GSDMs) play an essential role during the progression of colorectal cancer (CRC). However, it is not completely clear that how GSDMB, abundantly expressed in epithelial cells of gastrointestinal tract, regulates the tumorigenesis of CRC. A wealth of evidence linking GSDMB to the pathogenesis of cancer has come from genome-wide association studies. Here, we provide evidence that aberrantly upregulated GSDMB is responsible for suppressing the CRC progression by using in vitro cell and intestinal organoid, as well as in vivo GSDMB transgenic mice models. Mechanistically, GSDMB interacts with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which directly binds to and recognizes the 3'-UTR of dual specificity phosphatase 6 (DUSP6) mRNA, enhances the translation of DUSP6 protein and inhibits downstream ERK phosphorylation, thereby facilitating cell death and restraining cell proliferation. Our results suggest that GSDMB has potential as a novel therapeutic target for CRC treatment.

The expression levels of small extracellular vesicles (sEVs) are closely associated with several significant biological processes, which can be used as a crucial biomarker for cancer diagnosis, such as colorectal cancer. More efforts are still necessary to amplify sEV detection sensitivity, as their expression is minimal during the early stages of colorectal cancer. Through the integration of a catalytic assembly-triggered DNAzyme motor and gold nanoparticle (AuNP) aggregation, we have developed a triple signal amplified biosensor for the detection of sEVs. In this method, the catalytic assembly triggered DNAzyme motor continuously cleaved on the hairpin probe which is fixed on the surface of AuNPs, leaving a single-stranded sequence on the surface of AuNPs to induce the aggregation. This approach employs a triple signal amplification process to enhance the efficiency of the reaction and circumvent the issue of expensive and readily degradable proteases. The signal output system is based on dynamic light scattering technology, which enables ultra-sensitive detection of sEVs with a detection limit of 3.08 particles per μL. The present strategy exhibits significant potential for the analysis of a variety of additional analytes in clinical research disciplines due to its appealing analytical capabilities.

This study aims to explore the potential targets and anticancer mechanisms of dendrobine from Dendrobium nobile in the treatment of colorectal cancer through network pharmacology, and to experimentally validate its specific effects.

Initially, potential targets of dendrobine were identified using the ITCM Traditional Chinese Medicine database, while colorectal cancer-related genes were obtained from the NCBI Gene database, with the intersection of these datasets taken for further analysis. Functional enrichment analysis was conducted using the Metascape database, and a protein-protein interaction (PPI) network was constructed. Additionally, cell culture, cell proliferation assays, and wound healing assays were performed. The Wnt/β-catenin and NF-κB/COX-2/PGE2 signaling pathways were analyzed using PCR and Western blot experiments.

The PPI network constructed from 152 intersecting genes revealed that these genes play crucial roles in processes such as cell proliferation, apoptosis, and signal transduction. Cell-based assays demonstrated that dendrobine significantly inhibits the proliferation and migration of colorectal cancer cells. Furthermore, PCR and Western blot results indicated that dendrobine suppresses colorectal cancer cell proliferation and migration by modulating the Wnt/β-catenin and NF-κB/COX-2/PGE2 signaling pathways.

Dendrobine exhibits significant anticancer potential against colorectal cancer by regulating the Wnt/β-catenin and NF-κB/COX-2/PGE2 signaling pathways, providing a theoretical foundation and experimental evidence for its therapeutic application in colorectal cancer.

New technologies have shown that most of the genome comprises transcripts that cannot code for proteins and are referred to as non-coding RNAs (ncRNAs). Some ncRNAs, like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), are of substantial interest because of their critical function in controlling genes and numerous biological activities. The expression levels and function of miRNAs and lncRNAs are rigorously monitored throughout developmental processes and the maintenance of physiological homeostasis. Due to their critical roles, any dysregulation or changes in their expression can significantly influence the pathogenesis of various human diseases. The interactions between miRNAs and lncRNAs have been found to influence gene expression in various ways. These interactions significantly influence the understanding of disease etiology, cellular processes, and potential therapeutic targets. Different experimental and in silico methods can be used to investigate miRNA-lncRNA interactions. By aiding the elucidation of miRNA-lncRNA interactions and deepening the understanding of post-transcriptional gene regulation, researchers can open a new window for designing hypotheses, conducting experiments, and discovering methods for diagnosing and treating complex human diseases. This review briefly summarizes miRNA and lncRNA functions, discusses their interaction mechanisms, and examines the experimental and computational methods used to study these interactions. Additionally, we highlight significant studies on lncRNA and miRNA interactions in various diseases from 2000 to 2024, using the academic research databases such as PubMed, Google Scholar, ScienceDirect, and Scopus.

Olaparib (OLA) and regorafenib (REG) are metabolized by the CYP3A4 isoenzyme of cytochrome P450. Both drugs are also substrates and inhibitors of the membrane transporters P-glycoprotein and BCRP. Therefore, the potential concomitant use of OLA and REG may result in clinically relevant drug-drug interactions. Knowledge of the influence of membrane transporters and cytochrome P450 enzymes on the pharmacokinetics of drugs makes it possible to assess their impact on the efficacy and safety of therapy.

The study aimed to evaluate the bilateral pharmacokinetic interactions of OLA and REG and its active metabolites after a single administration in healthy rats.

The study was performed in male Wistar rats (n = 24) randomly divided into three groups: one study group, IREG+OLA (n = 8), received REG with OLA, and two control groups, IIREG (n = 8) and IIIOLA (n = 8), received REG and OLA, respectively. The concentrations of OLA, REG, REG-N-oxide (M-2), and N-desmethyl-REG-N-oxide (M-5) were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The values of the pharmacokinetic parameters of OLA, REG, M-2, and M-5 were determined by non-compartmental analysis with linear interpolation.

After OLA administration, the pharmacokinetic parameters of REG (AUC0-∞, tmax, and t0.5) increased significantly by 3.38-, 2.66-, and 1.82-fold, respectively. On the other hand, REG elimination parameters, i.e., kel and Cl/F, were significantly reduced in the study group by 1.77- and 1.70-fold, respectively. In the study group, Cmax and AUC0-t values were also 7.22- and 8.86-fold higher for M-2 and 16.32- and 17.83-fold higher for M-5, respectively. The Metabolite M-2/Parent and Metabolite M-5/Parent ratios for Cmax and AUC0-t increased by 6.52-, 10.74-, 28-, and 13-fold, respectively. After administration of OLA with REG, the Cmax, AUC0-t, and AUC0-∞ of OLA increased by 2.0-, 3.4-, and 3.4-fold, respectively, compared to the control group. Meanwhile, Cl/F and Vd/F of OLA were significantly decreased in the presence of REG.

OLA was shown to significantly affect the pharmacokinetics of REG and its active metabolites M-2 and M-5 in rats after co-administration of both drugs. There was also a significant effect of REG on the pharmacokinetics of OLA, which may have clinical relevance. The AUC ratios (study group/control group) were 3.41 and 3.39 for REG and OLA, respectively, indicating that REG and OLA were moderate inhibitors in this preclinical study. The results obtained need to be confirmed in clinical studies. This study may provide guidance on the safety of using both drugs in clinical practice.

Over the past century, colorectal cancer (CRC) has become one of the most devastating cancers impacting the human population. To gain a deeper understanding of the molecular mechanisms driving this solid tumor, researchers have increasingly turned their attention to the tumor microenvironment (TME). Spatial transcriptomics and proteomics have emerged as a particularly powerful technology for deciphering the complexity of CRC tumors, given that the TME and its spatial organization are critical determinants of disease progression and treatment response. Spatial transcriptomics enables high-resolution mapping of the whole transcriptome. While spatial proteomics maps protein expression and function across tissue sections. Together, they provide a detailed view of the molecular landscape and cellular interactions within the TME. In this review, we delve into recent advances in spatial biology technologies applied to CRC research, highlighting both the methodologies and the challenges associated with their use, such as the substantial tissue heterogeneity characteristic of CRC. We also discuss the limitations of current approaches and the need for novel computational tools to manage and interpret these complex datasets. To conclude, we emphasize the importance of further developing and integrating spatial transcriptomics into CRC precision medicine strategies to enhance therapeutic targeting and improve patient outcomes.

Computer-aided detection (CADe) devices have been shown to increase adenoma detection rates and adenomas per colonoscopy compared to standard colonoscopies. Questions remain about whether CADe colonoscopies are mainly increasing the detection of small, nonneoplastic lesions or if they are detecting more pathologically meaningful polyps. In this analysis, we compare the true histology rate (defined as polyps with confirmation of clinically relevant histopathology) of CADe-identified polyps with polyps identified during standard colonoscopies.

Using data from the SKOUT trial, we compared the true histology rate (THR) between CADe and standard colonoscopies. We also conducted a subgroup analysis by patient, procedural, and endoscopist factors. To account for multiple testing of comparisons, we used the false discovery rate.

A total of 1423 participants were included (CADe, n = 714; standard, n = 709). Overall, THR was similar between the CADe and standard colonoscopy arms for adenomas, sessile serrated lesions, and large hyperplastic polyps. Higher THR with CADe colonoscopy was observed in some subgroups for adenomas. Endoscopists with 11 to 20 years of experience and procedures occurring after 12 pm had significantly higher adenoma THRs in the CADe cohort. Patients younger than 65 years, male patients, and procedures with a withdrawal time of ≥8 minutes had borderline significance in the CADe device adenoma THR subgroup.

CADe colonoscopies may hold the key to improving endoscopic quality measures, provided that the polyps identified by the CADe device are those of clinical relevance. Although the benefit and significance in the CADe group were demonstrated in this analysis, further research is warranted to ensure that the true histology is maintained when applied in real-world applications.

The combination of trifluridine/tipiracil (FTD/TPI) and bevacizumab has demonstrated promising efficacy and safety in the treatment of colorectal cancer (CRC). This study aims to evaluate the cost-effectiveness of trifluridine/tipiracil combined with bevacizumab vs. trifluridine/tipiracil monotherapy as a third-line treatment regimen for colorectal cancer within the Chinese healthcare system, providing an economic basis for clinical application.

Based on data from the SUNLIGHT Phase III clinical trial, a dynamic Markov model was constructed with a cycle length of 4 weeks and a simulation duration of 10 years. Direct medical costs and quality-adjusted life years (QALYs) were calculated. The incremental cost-effectiveness ratio (ICER) was compared with the willingness-to-pay threshold (WTP = ¥268,200.00/QALY) to assess the economic viability of the treatment regimen. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to verify the robustness of the model results.

The cost of trifluridine/tipiracil combined with bevacizumab treatment (¥838,492.74) was higher than that of trifluridine/tipiracil monotherapy (¥357,396.97), with greater health benefits (2.45 QALYs vs. 1.54 QALYs). The ICER was ¥527,577.36/QALY, exceeding the willingness-to-pay threshold. One-way sensitivity analysis indicated that drug costs and utility values during the progression-free period significantly impacted model outputs. Probabilistic sensitivity analysis further confirmed the robustness of the results, showing that at a willingness-to-pay threshold of ¥494,000.00, the probability of the combined treatment being cost-effective was 50%.

Trifluridine/tipiracil combined with bevacizumab, as a third-line treatment for colorectal cancer, does not have a cost-effectiveness advantage compared to trifluridine/tipiracil monotherapy in economic evaluations.

Colorectal cancer (CRC) involves various genetic alterations, with liver metastasis posing a significant clinical challenge. Furthermore, CRC cells mostly show an increase in resistance to traditional treatments like chemotherapy. It is essential to investigate more advanced and effective therapies to prevent medication resistance and metastases and extend patient life. As a result, it is anticipated that small interfering RNAs (siRNAs) would be exceptional instruments that can control gene expression by RNA interference (RNAi). In eukaryotes, RNAi is a biological mechanism that destroys specific messenger RNA (mRNA) molecules, thereby inhibiting gene expression. In the management of CRC, this method of treatment represents a potential therapeutic agent. However, it is important to acknowledge that siRNA therapies have significant issues, such as low serum stability and nonspecific absorption into biological systems. Delivery mechanisms are thus being created to address these issues. In the current work, we address the potential benefits of siRNA therapy and outline the difficulties in treating CRCby focusing on the primary signaling pathways linked to metastasis as well as genes implicated in the multi-drug resistance (MDR) process.

Dihydroartemisinin (DHA), a compound extracted from the herbal medicine Artemisia annua, has shown promise as a clinical treatment strategy for colorectal cancer. However, its clinical use is hindered by its low water solubility and bioavailability. A pH/glutathione (GSH) dual-responsive nano-herb delivery system (PMDC NPs) has been developed for the targeted delivery of DHA, accompanied by abundant carbon monoxide (CO) release. Due to the passive enhanced permeability and retention (EPR) effect and active targeting mediated by pHCT74 peptide binding to overexpressed α-enolase on colorectal cancer cells, the pHCT74/MOF-5@DHA&CORM-401 nanoparticles (PMDC NPs) exhibited specific targeting capacity against colorectal cancer cells. Once reaching the tumor site, the pH/GSH dual-responsive behavior of metal-organic framework-5 (MOF-5) enabled the rapid release of cargo, including DHA and CORM-401, in the acidic tumor microenvironment. Subsequently, DHA stimulated CORM-401 to release CO, which facilitated ROS-induced ferroptosis and apoptosis, leading to immunogenic cell death (ICD) and a sustained antitumor response through the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Overall, PMDC NPs enhanced the bioavailability of DHA and exhibited outstanding therapeutic effectiveness both in vitro and in vivo, indicating their potential as a promising and feasible alternative for synergistic treatment with immunotherapy and gas therapy in the clinical management of colorectal cancer.

Colorectal cancer (CRC) represents the second leading cause of cancer-related mortality worldwide, with a significant portion of patients presenting with metastatic disease at diagnosis. Resistance to initial anti-EGFR therapy, a key treatment for RAS wild-type metastatic CRC, remains a major challenge. This study aimed to assess the efficacy and safety of rechallenge with anti-EGFR therapy in patients with metastatic CRC who have progressed after prior treatments.

A systematic search was conducted across PubMed, Web of Science, Cochrane, and Scopus. Studies were included if they were randomized controlled trials (RCTs) or observational studies involving patients with EGFR-mutated metastatic CRC who received anti-EGFR therapy as a rechallenge. Endpoints included objective response rate (ORR), disease control rate (DCR), and the incidence of adverse events. Statistical analyses were performed using the DerSimonian/Laird random effect model, with heterogeneity assessed via I2 statistics. R, version 4.2.3, was used for statistical analyses.

Fourteen studies were included with 520 patients; 50.3% were male, and the median age was 63 years old. The median progression-free survival (mPFS) ranged between 2.4 and 4.9 months, while the median overall survival (mOS) ranged from 5 to 17.8 months. Our pooled analysis demonstrated an objective response rate (ORR) of 17.70% (95% CI, 8.58-26.82%) and a disease control rate (DCR) of 61.72% (95% CI, 53.32-70.11%), both with significant heterogeneity (I2, 84% and 80%, respectively; p < 0.01). In the subgroup analysis, cetuximab showed an ORR of 18.31% (95% CI, 4.67-31.94%), and panitumumab an ORR of 10.9% (95% CI, 0.00-26.82%), while the combination of both resulted in an ORR of 29.24% (95% CI, 0.00-65.84%). For DCR, cetuximab resulted in 62.1% (95% CI, 49.32-74.87%), panitumumab in 63.05% (95% CI, 52.13-73.97%), and the combination in 60.34% (95% CI, 31.92-88.77%), all with significant heterogeneity. Adverse events included anemia (15.39%), diarrhea (4.20%), hypomagnesemia (6.40%), neutropenia (22.57%), and skin rash (13.22%).

Rechallenge with anti-EGFR therapy in metastatic CRC patients shows moderate efficacy with manageable safety profiles. These findings highlight the need for careful patient selection and monitoring to optimize outcomes. Further studies are warranted to refine strategies for maximizing the therapeutic benefits of anti-EGFR rechallenge.

Glucose is an important energy source for tumors, however the molecular mechanisms by which tumor cells regulate glucose uptake remain unclear. In this study, we aimed to investigate the regulation mechanism of the WNT7B/β-catenin pathway for glucose transporter 1 (GLUT1)-mediated glucose metabolism in colorectal cancer. Here, we found that WNT7B expression levels were significantly increased in colorectal cancer tissues and closely associated with the clinical stage and lymph node metastasis in patients with colorectal cancer. Next, we confirmed that WNT7B significantly increased the glucose consumption and lactic acid levels in SW480 cells by overexpressing WNT7B. Additionally, gene and protein levels of GLUT1 were increased in WNT7B-overexpressing SW480 cells. However, WNT7B knockdown reversed these effects. WNT7B also enhanced GLUT1-mediated cell proliferation, invasion, and migration. WNT7B overexpression inhibited the effect of glucose deprivation on apoptosis. The WNT/β-catenin signaling pathway inhibitor, LGK974, inhibited WNT7B secretion, leading to GLUT1 levels downregulation and promotion of cell apoptosis. Ectopic tumor xenograft model experiments revealed that WNT7B promoted tumor progression in mice. Overall, our results suggest that WNT7B promotes β-catenin entry into the nucleus to initiates GLUT1 transcription, increases glucose transport and consumption, and enhances aerobic glycolysis, thus promoting tumor progression in colorectal cancer cells.

It is projected that, by 2040, the number of new cases of colorectal cancer (CRC) will increase to 3.2 million, and the number of deaths to 1.6 million, highlighting the need for prevention strategies, early detection and adequate follow-up. In this study, we aimed to provide an overview of the progress in personalized medicine of CRC in Serbia, with results and insights from the Institute for Oncology and Radiology of Serbia (IORS), and to propose guidance for tackling observed challenges in the future.

Epidemiological data were derived from official global and national cancer registries and IORS electronic medical records. Germline genetic testing for Lynch syndrome was performed by Next Generation Sequencing. RAS and BRAF mutation analyses were performed using qPCR diagnostic kits.

Epidemiology and risk factors, prevention and early detection programs, as well as treatment options and scientific advances have been described in detail. Out of 103 patients who underwent germline testing for Lynch syndrome, 19 (18.4%) showed a mutation in MMR genes with pathogenic or likely pathogenic significance and 8 (7.8%) in other CRC-associated genes (APC, CHEK2, MUTYH). Of 6369 tested patients, 50.43% had a mutation in KRAS or NRAS genes, while 9.54% had the V600 mutation in the BRAF gene.

Although significant improvements in CRC management have occurred globally in recent years, a strategic approach leading to population-based systemic solutions is required. The high incidence of young-onset CRC and the growing elderly population due to a rise in life expectancy will be especially important factors for countries with limited healthcare resources like Serbia.