Endoplasmic reticulum stress (ERS) has been implicated in the pathogenesis of various cancers, including colon cancer, by regulating tumor cell survival, growth, and immune response. However, the specific genes involved in ERS that could serve as prognostic markers in colon cancer remain underexplored. This study aims to identify and validate endoplasmic reticulum stress related genes (ERSRGs) in colon cancer that correlate with patient prognosis, thereby enhancing the understanding of ERS in oncological outcomes and potential therapeutic targeting. We utilized bioinformatics analyses to identify ERSRGs from publicly available colon cancer datasets. Differential expression analysis and survival analysis were performed to assess the prognostic significance of these genes. Validation was conducted through quantitative real-time PCR (RT-qPCR) on selected colon cancer cell lines. Our study identified nine ERS related genes (ASNS, ATF4, ATF6B, BOK, CLU, DDIT3, MANF, SLC39A14, TRAF2) involved in critical pathways including IL-12, PI3K-AKT, IL-7, and IL-23 signaling, and linked to 1-, 3-, and 5-year survival of patients with colon cancer. A multivariate Cox model based on these ERS related genes demonstrated significant prognostic power. Further, TRAF2 strong correlated with immune cells infiltration, suggesting its potential roles in modulating immune responses in the tumor microenvironment. The RT-qPCR validation confirmed the differential expression of these genes in human colon cancer cell lines versus human normal colonic epithelial cell line. The identified ERSRGs could serve as valuable prognostic markers and may offer new insights into the therapeutic targeting of ERS in colon cancer.

The present study aimed to investigate clinicopathological factors affecting local recurrence and survival in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) and to create a risk-scoring model predicting local control (LC) and survival. The clinical and pathological data of 115 patients who received nCRT for LARC between February 2010 and December 2020 were reviewed retrospectively. A risk-scoring model was developed to predict LC and survival using statistically significant prognostic factors in univariate and multivariate analyses. In the multivariate analysis, the LC rate was improved in patients with a good pathological response to nCRT. By contrast, the disease-free survival (DFS) rate was significantly worse in patients with perineural invasion (PNI). The overall survival (OS) rate was significantly worse in patients who were >60 years of age, who had tumors ≥5 cm, who were PNI-positive and who had pathological N2 stage disease. Patients were grouped to analyze the ability of the scoring system to predict LC and survival. The total score was derived by assigning points to the prognostic factors in univariate and multivariate analyses and was subsequently divided into three groups according to tertile. The median LC times in groups 1-3 were significantly different at 143.6, 97.2 and 93.6 months, respectively. The median DFS times in groups 1-3 were significantly different at 136.1, 108.5 and 67.2 months, respectively, while the median OS times in groups 1-3 were significantly different at 138.3, 87.2 and 64.6 months, respectively. In conclusion, risk score modeling with prognostic factors effectively determined the difference in LC and survival between the groups. Adding effective systemic therapy to nCRT may improve results, especially in patients with multiple poor prognostic factors, including larger tumors, PNI and multiple nodal involvement.

Fusobacterium nucleatum (Fn), an oral anaerobic commensal, has recently been identified as a crucial oncogenic contributor to colorectal cancer pathogenesis through its ectopic colonization in the gastrointestinal tract. Accumulating evidence reveals its multifaceted involvement in colorectal cancer initiation, progression, metastasis, and therapeutic resistance to conventional treatments, including chemotherapy, radiotherapy, and immunotherapy. This perspective highlights recent advances in anti-Fn strategies, including small-molecule inhibitors, nanomedicines, and biopharmaceuticals, while critically analyzing the translational barriers in developing targeted antimicrobial interventions. We further propose potential strategies to overcome current challenges in Fn modulation, aiming to pave the way for more effective therapeutic interventions and better clinical outcomes.

Identifying tumor budding (TB) in colorectal cancer (CRC) is vital for better prognostic assessment as it may signify the initial stage of metastasis. Despite its importance, TB detection remains challenging due to subjectivity in manual evaluations. Identifying TBs remains difficult, especially at high magnification levels, leading to inconsistencies in prognosis. To address these issues, we propose an automated system for TB classification using deep learning.

We trained a deep learning model to identify TBs through weakly supervised learning by aggregating positive and negative bags from the tumor invasive front. We assessed various foundation models for feature extraction and compared their performance. Attention heatmaps generated by attention-based multi-instance learning (ABMIL) were analyzed to verify alignment with TBs, providing insights into the interpretability of the features. The dataset includes 29 WSIs for training and 70 whole slide images (WSIs) for the hold-out test set.

In six-fold cross-validation, Phikon-v2 achieved the highest average AUC (0.984 ± 0.003), precision (0.876 ± 0.004), and recall (0.947 ± 0.009). Phikon-v2 again achieved the highest AUC (0.979) and precision (0.980) on the external hold-out test set. Moreover, its recall rate (0.910) was still higher than that of UNI's (0.879). UNI exhibited a balanced performance on the hold-out test set, with an AUC of 0.960 and a precision of 0.968. CtransPath showed strong precision on the external hold-out test set (0.947) but had a slightly lower recall (0.911).

The proposed technique enhances the accuracy of TB assessment, offering potential applications for CRC and other cancer types.

Malignant bowel obstruction (MBO) is a common and complex condition in clinical practice, which seriously affects the quality of life and prognosis of patients. However, the current lack of effective prognostic models for MBO has greatly limited clinical precision treatment and patient management. Focusing on this issue, this study aims to construct and validate a prognostic model for the overall survival (OS) of MBO patients, providing crucial support for clinical decision - making and improving the prognosis of patients. In this study, 41 items of real - world data from 192 patients in the Affiliated Hospital of Nantong University from January 2022 to January 2024 were collected, including 39 independent variables, survival time, and survival status. Subsequently, the patients were randomly divided into groups at a ratio of 7:3. Predictor variables were screened using the Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression, and then a Cox model was constructed. The model was validated using the Concordance index (C - index), time - dependent Receiver Operating Characteristic (ROC) curve, and Decision Curve Analysis (DCA). Finally, a nomogram of the model was created. The study found that significant risk factors affecting patient mortality included chemoradiotherapy (β = - 1.24; HR = 0.29;95%CI, 0.14-0.59), conservative treatment (β = 1.34; HR = 3.81; 95%CI, 1.69-8.55), new cases (β = - 0.96; HR = 0.38; 95%CI, 0.19-0.77), AJCC T stage 4 (β = 2.16; HR = 8.64; 95%CI, 1.47-50.76), red blood cell count (RBC, β = - 0.63; HR = 0.53; ; 95%CI, 0.38-0.80), prothrombin time (PT, β = 0.37; HR = 1.45; ; 95%CI, 1.07-1.97), aspartate aminotransferase (AST, β = 0.01; HR = 1.01; 95%CI, 1.00-1.02), and intestinal necrosis (β = 1.73; HR = 5.62; 95%CI, 1.11-28.27). In the development set, the AUC and C - index values of the prognostic models for 30 - day, 90 - day, and 180 - day are 0.87, 0.94, and 0.92 respectively. In the validation set, the corresponding values are 0.83, 0.96, and 0.89. The results of DCA analysis indicated that the model was reliable and could effectively predict the 30 - day, 90 - day, and 180 - day survival periods of MBO patients. This study successfully constructed and validated a prognostic model for the overall survival of MBO patients. This model identified multiple key prognostic factors and exhibited good predictive performance. It provides important reference for clinicians to predict the survival period of MBO patients and develop personalized treatment plans, and is expected to improve the clinical outcomes of MBO patients.

Tumor mutations and the composition of the tumor microenvironment have prognostic and therapeutic significance in colorectal cancer (CRC). However, immunotherapy remains a challenge for patients with proficient mismatch repair (pMMR) CRC. In this paper, the association between tumor-infiltrating lymphocytes (TILs) and tumor mutations on survival outcomes in patients with localized pMMR CRC was examined.

A systematic review of the literature and a meta-analysis were conducted in accordance with the PRISMA guidelines. The literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. The outcomes of interest were overall survival, disease-free survival, and cancer-specific survival. The risk of bias was assessed through the Newcastle-Ottawa Scale and the quality of the cumulative evidence was evaluated through the modified GRADE approach.

In total, 8498 articles were screened for eligibility and 44 articles were included in the meta-analysis with 33,704 patients in total. Patients with high infiltration of any TILs showed significantly improved overall survival (HR = 0.57, 95 % CI: 0.49-0.67, I2: 0 %), especially for the subgroup of CD3 + (HR = 0.52, 95 % CI: 0.38-0.71, I2: 0 %) and CD8 + (HR = 0.60, 95 % CI: 0.37-0.99, I2: 10 %) TILs. Patients with BRAF mutation (HR = 2.68, 95 % CI: 1.47-4.89, I2: 83 %) and KRAS mutation (HR = 1.25, 95 % CI: 1.18-1.33, I2: 0 %) showed decreased overall survival.

High infiltration of TILs, especially CD3 + and CD8 + , was associated with significantly improved survival, while BRAF and KRAS mutations were correlated with worse survival outcomes for patients with non-metastatic pMMR CRC.

To evaluate the clinical value of multi-slice spiral CT in preoperative TNN staging and postoperative recurrence and metastasis of colon carcinoma, and to provide evidence for the reliability of CT in the diagnosis of colon carcinoma METHODS: 89 patients with colon carcinoma diagnosed pathologically in our hospital from July 2020 to April 2023 were selected retrospectively. The preoperative TNN staging and postoperative recurrence and metastasis were monitored by 64 row 128 layer spiral CT. The diagnostic coincidence rate, TNM staging coincidence rate and postoperative recurrent TNM staging accuracy were evaluated according to the pathological diagnosis RESULTS: The diagnostic coincidence rate of multi-slice spiral CT was 97.8 % (87/89), and the detection rate of lymph nodes was 86.1 % (31/36). The coincidence rate of T staging was 93.3 % (83/89), N staging was 91.0 % (81/89), M staging was 100 % (Kappa=0.897,0.879, 1.000). The diagnosis of recurrent TNM stage was consistent (Kappa=0.893, 0.801, 1.000) CONCLUSION: Multi-slice spiral CT is of high diagnostic coincidence rate, high accuracy of TNM staging and rapid noninvasive examination. It can obtain reliable results in preoperative staging and postoperative recurrence and metastasis diagnosis, which is worth popularizing in clinic.

Background/Objectives: Colorectal cancer (CRC) is a major global health concern with rising incidence and mortality. MicroRNAs (miRNAs) play key roles in tumor progression, invasion, and metastasis. This study aimed to analyze the expression of miR-101-3p, miR-106a-5p, and miR-326 in CRC patients and assess their association with tumor grading and tissue invasion. Methods: A total of 40 CRC patients were included in the study. miRNA expression levels were measured using quantitative reverse transcription PCR (qRT-PCR). Statistical analyses, including regression models, were performed to evaluate correlations between miRNA expression, tumor grade, and invasion patterns. Results: MiR-101-3p was significantly downregulated in advanced tumors, while miR-106a-5p expression peaked in Grade 2 CRC. MiR-326 expression was associated with organ metastasis. Regression models confirmed complex interaction patterns among these miRNAs, suggesting their potential role in CRC progression. Conclusions: These findings indicate that miR-101-3p, miR-106a-5p, and miR-326 are associated with CRC severity and invasion. Their expression patterns suggest potential utility as biomarkers for early detection and targeted therapies. Further studies with larger cohorts are needed to validate these results and explore their clinical applications.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths globally, with incidence and mortality rates exhibiting geographical disparities.

This study aims to outline the pathological profile of CRC.

The study was conducted in the anatomopathological laboratories of the Souss Massa region (SMR) in Morocco.

The study examined the epidemiological and anatomopathological profile of CRC among patients diagnosed. We reviewed 238 anatomopathological results during the study period. Fisher's exact test and analysis of variance were performed using Statistical Package for Social Sciences (SPSS) version 20.

Rectum and sigmoid colon were the most common sites for CRC (76.9%), with adenocarcinomas emerging as the predominant histological variant (93.3%). Most tumours were moderately differentiated (96.6%), with many (83.1%) in advanced stages (T3, T4). The presence of vascular embolism in 31.9% of patients indicates aggressive disease progression. Additionally, the study discerned a slight male dominance (52.9%) in the prevalence of CRC and an average age of 59 among patients. Notably, sex showed a significant association with the manifestation of CRC across various organs (p = 0.028), as did histological types across different organs (p = 0.010). Age-related analysis found older patients (over 50 years) with advanced-stage CRC more frequently.

The histopathological features of these tumours are associated with an alarming delay in diagnosis and a significant presence of vascular embolism in patients.

Delay in diagnosis of CRC is significant in the SMR. There is an urgent need to strengthen screening strategies and examine social determinants of health for earlier diagnosis.

Immunotherapy of cancer is now an essential pillar of treatment for patients with many individual tumor types. Novel immune targets and technical advances are driving a rapid exploration of new treatment strategies incorporating immune agents in cancer clinical practice. Immunotherapies perturb a complex system of interactions among genomically unstable tumor cells, diverse cells within the tumor microenvironment including the systemic adaptive and innate immune cells. The drive to develop increasingly effective immunotherapy regimens is tempered by the risk of immune-related adverse events. Evidence-based biomarkers that measure the potential for therapeutic response and/or toxicity are critical to guide optimal patient care and contextualize the results of immunotherapy clinical trials. Responding to the lack of guidance on biomarker testing in early-phase immunotherapy clinical trials, we propose a definition and listing of essential biomarkers recommended for inclusion in all such protocols. These recommendations are based on consensus provided by the Society for Immunotherapy of Cancer (SITC) Clinical Immuno-Oncology Network (SCION) faculty with input from the SITC Pathology and Biomarker Committees and the Journal for ImmunoTherapy of Cancer readership. A consensus-based selection of essential biomarkers was conducted using a Delphi survey of SCION faculty. Regular updates to these recommendations are planned. The inaugural list of essential biomarkers includes complete blood count with differential to generate a neutrophil-to-lymphocyte ratio or systemic immune-inflammation index, serum lactate dehydrogenase and albumin, programmed death-ligand 1 immunohistochemistry, microsatellite stability assessment, and tumor mutational burden. Inclusion of these biomarkers across early-phase immunotherapy clinical trials will capture variation among trials, provide deeper insight into the novel and established therapies, and support improved patient selection and stratification for later-phase clinical trials.

Background: Patients with rectal cancer may be exposed to a loss of muscle strength and quality. This study aimed to assess the role of preoperative CT-based sarcopenia on postoperative clinical, pathological, and oncological outcomes after rectal cancer surgery. Methods: This retrospective monocentric study included patients who underwent elective oncologic resection for rectal adenocarcinoma between 01/2014 and 03/2022. The skeletal muscle index (SMI) was measured using CT at the third lumbar vertebral level, and sarcopenia was defined based on pre-established sex-specific cut-offs. Patients with sarcopenia were compared to those without sarcopenia in terms of outcomes. A Cox proportional hazard regression analysis was used to determine the independent prognostic factors of disease-free survival (DFS) and overall survival (OS). Results: A total of 208 patients were included, and 123 (59%) had preoperative sarcopenia. Patients with sarcopenia were significantly older (66 vs. 61 years, p = 0.003), had lower BMI (24 vs. 28 kg/m2, p < 0.001), and were mainly men (76 vs. 48%, p < 0.001). There was no difference in overall and major complication rates between the sarcopenia and non-sarcopenia group (43 vs. 37%, p = 0.389, and 17 vs. 17%, p = 1.000, respectively). Preoperative and postoperative features related to rectal surgery were comparable. The only predictive factor impacting OS was R1/R2 resection (HR 4.915, 95% CI, 1.141-11.282, p < 0.001), while sarcopenia (HR 2.013, 95% CI 0.972-4.173, p = 0.050) and T3/T4 status (HR 2.108, 95% CI 1.058-4.203, p = 0.034) were independently associated with DFS. Conclusions: A majority of patients undergoing rectal cancer surgery had preoperative CT-based sarcopenia. In this cohort, sarcopenia had no impact on postoperative morbidity and OS but was independently associated with DFS.

BackgroundRadiomics analysis is widely used to assess tumor prognosis.PurposeTo explore the value of computed tomography (CT) radiomics nomogram in predicting disease-free survival (DFS) of patients with colorectal cancer (CRC) after operation.Material and MethodsA total of 522 CRC patients from three centers were retrospectively included. Radiomics features were extracted from CT images, and the least absolute shrinkage and selection operator Cox regression algorithm was employed to select radiomics features. Clinical risk factors associated with DFS were selected through univariate and multivariate Cox regression analysis to build the clinical model. A predictive nomogram was developed by amalgamating pertinent clinical risk factors and radiomics features. The predictive performance of the nomogram was evaluated using the C-index, calibration curve, and decision curve. DFS probabilities were estimated using the Kaplan-Meier method.ResultsIntegrating the retained eight radiomics features and three clinical risk factors (pathological N stage, microsatellite instability, perineural invasion), a nomogram was constructed. The C-index for the nomogram were 0.819 (95% CI=0.794-0.844), 0.782 (95% CI=0.740-0.824), 0.786 (95% CI=0.753-0.819), and 0.803 (95% CI=0.765-0.841) in the training set, internal validation set, external validation set 1, and external validation set 2, respectively. The calibration curves demonstrated a favorable congruence between the predicted and observed values as depicted by the nomogram. The decision curve analysis underscored that the nomogram yielded a heightened clinical net benefit.ConclusionThe constructed radiomics nomogram, amalgamating the radiomics features and clinical risk factors, exhibited commendable performance in the individualized prediction of postoperative DFS in CRC patients.

Globally, colorectal cancer (CRC) continues to rank among the leading causes of cancer-related death. Systemic toxicity, multidrug resistance, and nonspecific targeting often pose challenges to conventional therapy for CRC. Because it is a complex disease with a complex genetic and environmental pathophysiology, advanced therapeutic strategies are needed. Nanotechnology presents a potential solution that may maximize therapeutic efficacy while minimizing negative effects by enabling personalized delivery of anticancer drugs. This review focuses on recent developments in colorectal drug delivery systems based on nanotechnology. Numerous nanomaterials, including liposomes, dendrimers, micelles, exosomes, and gold nanoparticles, are developed and used. Distinctive characteristics of mentioned nanocarriers are discussed along with strategies that can be employed for enhancing the delivery of drugs to colorectal cancer cells. The review also quotes the most relevant preclinical and clinical studies that show how these nanomaterials improve drug solubility, stability, and targeted delivery while overcoming the shortcomings of conventional therapies. Nanotechnology has made CRC treatment very efficient and advanced, which has opened up new possibilities for targeted drug delivery. Preclinical and clinical studies have also proved that the use of nano-formulations in colon-specific delivery systems have significant results, indicating potential for better patient outcomes. Future research can be done in order to overcome the hurdles regarding biocompatibility, expansion, and regulatory challenges. Large-scale clinical trials and nanomaterial formulation optimization should be the main goals of future research to confirm the efficacy and safety of these novel treatments.

Metformin, widely used for the treatment of type 2 diabetes, has recently gained attention for its potential anticancer properties. Several studies have shown that metformin treatment inhibits cell viability in colon adenocarcinoma (COAD); however, the research related to the tumor-node-metastasis (TNM) stage is limited. As COAD is frequently diagnosed at an advanced stage, understanding the genetic factors that regulate the pathogenesis of COAD at each TNM stage and the effects of metformin for potential treatment. Therefore, we identified differentially expressed factors at the TNM stage in metformin-treated COAD cells and investigated their regulatory mechanisms using microRNAs (miRNAs). Through bioinformatics analyses, four-jointed box kinase 1 (FJX1) and hsa-miR-1306-3p were identified as differentially expressed in COAD upon metformin treatment. Metformin treatment significantly reduced cell viability, with an observed decrease of approximately 50%. Analysis using quantitative real-time PCR showed an increase in hsa-miR-1306-3p and a decrease in FJX1 expression upon metformin treatment compared to untreated cells. Luciferase assay confirmed the sequence-specific binding of hsa-miR-1306-3p to FJX1. These findings highlight the potential of metformin as a therapeutic agent for COAD by modulating FJX1 expression via upregulation of hsa-miR-1306-3p, revealing novel avenues for COAD treatment.

There are various histological characteristics which have been proposed to predict the survival rate in colon cancer. However, there is no definitive model to accurately predict the survival. Therefore, it is important to find out one model for the prediction of survival in colon cancer which may also include the preoperative, and operative factors in addition to histopathology.

To construct a postoperative recurrence prediction model for patients with T1 colorectal cancer after endoscopic resection and surgical operation via survival machine learning algorithms.

Based on two tertiary-level affiliated hospitals, case data of 580 patients with T1 colorectal cancer treated by endoscopic resection and surgery were obtained, and patients' personal information, treatment modalities, and pathology-related information were extracted. After Boruta's algorithmic feature selection, predictors with significant contributions were identified. The patients were divided into a train set and a test set at a ratio of 7:3, and five survival machine learning models were subsequently built, namely, Randomized Survival Forest (RSF), Gradient Boosting (GB), Survival Tree (ST), CoxPH and Coxnet. Interpretability analysis of the model is based on the SHAP algorithm.

Patients at high risk of lymph node metastasis have a poor prognosis, but different treatment modalities do not significantly affect the prognosis of patients with recurrence. The Random Survival Forest model shows better performance, with a C-index and Integrated Brier Score of 0.848 and 0.098 in the test set, respectively, and its time-dependent AUC is 0.918. The interpretability analysis of the model revealed that submucosal invasion depth < 1000 μm, tumor budding grade of BD1, lymphovascular invasion and perineural invasion are absent, well differentiated cancer cells, and tumor size < 20 mm have positive effects on the model, lts negative gain characteristics are a contributing factor to patient relapse.

The prognostic model constructed via survival machine learning for patients with T1 colorectal cancer has good performance, and can provide accurate individualized predictions.

This study aimed to investigate the association between lymph node yield (LNY) and cancer-specific survival (CSS) in patients with T1 colorectal cancer (CRC) via data from two large cohorts.

We analyzed data from 4186 patients in the SEER cohort (2010-2015) and 533 patients from CHCAMS (2014-2019). Patients were categorized into two groups based on whether their LNY was above or below the guideline-recommended threshold of 12 nodes. Propensity score matching was used to adjust for confounding factors, and survival analysis was conducted using Kaplan-Meier and Cox proportional hazards models.

No significant difference in CSS was found between patients with LNY ≥ 12 and those with LNY < 12 in either the SEER or CHCAMS cohorts (log-rank P > 0.05 for both). After multivariate adjustment, LNY was not independently associated with CSS. Factors such as age, tumor location, elevated preoperative CEA levels, and adjuvant chemotherapy were significant prognostic factors in the SEER cohort. In the CHCAMS cohort, lymph node metastasis (LNM) emerged as the sole independent predictor of CSS.

Our findings suggest that LNY is not significantly associated with CSS in patients with T1 CRC, challenging the necessity of adhering to the 12-node benchmark for early-stage disease. Instead, factors such as tumor biology, LNM, and patient demographics may be more relevant in determining survival outcomes. Further prospective studies are needed to validate these findings and refine guidelines for lymph node assessment in early-stage CRC.

Microsatellite high instability/deficient mismatch repair (MSI-H/dMMR) colorectal cancer (CRC) has an active tumor microenvironment, rendering it more sensitive to immune checkpoint inhibitors. Given that studies involving patients with MSI-H colorectal cancer with RAS mutations are scarce, we explored the effect of RAS mutations on the TME in patients with MSI-H/dMMR cancer and identified potential prognostic factors.

Seventy-five patients diagnosed with MSI-H/dMMR colorectal cancer were retrospectively enrolled and divided into RAS-mutant and -wild-type groups. The expression levels of CD11c+ dendritic cells, CD4+ T cells, CD8+ T cells, and regulatory T cell (Treg) markers were detected, and prognostic factors were analyzed.

RAS-mutant MSI-H colorectal patients were more likely to have: (1) higher platelet values; (2) shorter disease-free survival (DFS); (3) lower infiltrated numbers of CD11c+ dendritic cells, CD4+ T lymphocytes, and CD8+ T lymphocytes, and higher infiltrated numbers of Foxp3+ Treg cells. In MSI-H/dMMR CRC patients: (1) the high CD11c + , CD4 +,  and CD8 +  cells infiltration group had longer DFS than the low-infiltration group, and Foxp3 + cells infiltration was not significantly correlated with DFS; (2) the RAS mutation status, number of CD11c+ cells infiltrated, and carbohydrate antigen 19-9 (CA19-9) level were the potential prognostic factors.

RAS mutations in patients with MSI-H/dMMR CRC may reduce the infiltration of CD11c+ dendritic cells, CD4+ T cells, and CD8+ T cells, and increase the infiltration of Foxp3+ Treg cells to affect the tumor microenvironment of patients. RAS gene status, CD11c + cells infiltration, and CA19-9 level were potential prognostic factors for MSI-H/dMMR CRC.

Despite TNM (Tumour, Node, Metastasis) classification being the gold standard for estimating the prognosis of early-stage colorectal cancer, significant variability in long-term survival persists among patients within the same TNM stage, underscoring the importance of the disease's biological heterogeneity and the need for novel markers. This study investigates the determinants of 5-year mortality in patients with colon or rectal cancer through the analysis of 448 diagnostic tumour samples from a prospective multicentre cohort. We assessed sociodemographic, clinical, and pathological data, as well as the apoptotic index (AI) measured by the terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) technique. Overall survival was the primary outcome, and Cox regression was used to estimate the hazard ratio (HR). Multivariate 5-year survival analysis identified the highest risk associated with TNM stages IV [p<0.001, HR 12.06, confidence interval (CI) 5.75-25.31] and III (p<0.001, HR 3.52, CI 1.88-6.62), followed by an AI >1.8% (p<0.001, HR 2.16, CI 1.46-3.20), male biological sex (p<0.05, HR 1.58, CI 1.05-2.37), tumour location on the right colon (p<0.024, HR 1.55, CI 1.06-2.27), and age (p<0.001, HR 1.05, CI 1.04-1.07). Our findings underscore the long-term prognostic value of a high AI as a determinant of poor prognosis in colorectal cancer and highlight the need to refine conventional prognostic markers to enable more precise risk stratification.

Colorectal cancer (CRC) is one of the most common and deadly forms of cancer worldwide, necessitating accurate and early detection to improve treatment outcomes. Traditional diagnostic methods often rely on manual examination of pathological images, which can be time-consuming and prone to human error. This study presents an advanced approach for colorectal cancer detection using a Random Hinge Exponential Distribution coupled Attention Network (RHED-CANet) on pathological images. The input dataset is sourced from the TCGA-CRC-DX cohort and the CRC dataset, both widely recognized for their comprehensive coverage of colorectal cancer cases. Pre-processing and feature extraction are performed using a Modified Square Root Sage-Husa Adaptive Kalman Filter combined with a Spike-Driven Transformer, enhancing noise reduction and feature clarity. Segmentation is achieved through an EfficientNetV2L Inception Transformer, ensuring precise delineation of cancerous regions. The final classification utilizes the RHED-CANet, a network tailored to handle the complexities of pathological data with high accuracy. This methodology achieved remarkable results, with an accuracy of 99.9% and a precision of 99.7%. These performance metrics underscore the method's ability to minimize false positives and enhance diagnostic accuracy. The proposed approach offers significant advantages, including a reduction in diagnostic time and a substantial improvement in detection accuracy, making it a promising tool for clinical applications. Despite its excellent accuracy, the suggested RHED-CANet technique has drawbacks, such as overfitting the TCGA-CRC-DX and CRC datasets by reducing generalizability on other datasets comprising other cancer types or image qualities. The actual application of the techniques in real-time clinical applications may be hampered by this computational load, especially in settings with limited resources, and the model's potential computational complexity due to multiple advanced processing steps. Additionally, the efficiency of training may be impacted by biased inputs, particularly for minor CRC subtypes.

Lymphovascular invasion (LVI) is a well-known risk factor in colorectal cancer that is associated with a worse prognosis. The present study aimed to assess the characteristics of patients with LVI-positive colon cancer according to the status of nodal metastases and to study the association between LVI-nodal status and survival.

This retrospective study assessed the association between LVI and lymph node metastases in colon cancer, using data from the National Cancer Database. Patients were classified according to the pathological N stage into pN0 and pN1-2. The risk factors for LVI were determined in each group using multivariable regression analyses. The primary outcome was LVI and the secondary outcome was 5-year overall survival (OS). A modification of the tumour, node, metastasis (TNM) staging system that incorporates LVI in each stage was proposed.

The study included 357 724 patients (51.1% female, median age 70 years). LVI was detected in 11.6% and 52.5% of patients with node-negative and node-positive disease, respectively. The independent predictors of LVI in pN0 stage were poorly differentiated carcinomas (OR: 3.6, p < 0.001), undifferentiated carcinomas (OR: 3.3, p < 0.001), mucinous carcinomas (OR: 0.61, p < 0.001), and perineural invasion (OR: 4.2, p < 0.001). The independent predictors of LVI in pN1-2 disease were poorly differentiated carcinomas (OR: 2.36, p < 0.001), undifferentiated carcinomas (OR: 3.23, p < 0.001), and perineural invasion (OR: 3.33, p < 0.001). LVI was significantly associated with worse 5-year OS and the adverse survival impact of LVI was higher in pN1-2 disease (HR: 1.47, p < 0.001) than in pN0 disease (HR: 1.28, p < 0.001). When LVI was present, the 5-year OS was reduced by 1.5% in stage I, 5.6% in stage II, and 11.5% in stage III.

LVI was more prevalent in patients with colon cancer with lymph node metastases than in patients with node-negative disease. However, LVI was not detected in approximately half of patients with nodal disease. The adverse survival effect of LVI was proportional to the stage of colon cancer.

The prognosis of colorectal cancer (CRC) patients is notably influenced by both inflammation and nutritional status. The prognostic nutritional index (PNI) and systemic inflammatory response index (SIRI) have been reported in prognostic studies of various tumors. However, the efficacy of the combination of the two in predicting the prognosis of CRC patients has not been studied.

To evaluate the effectiveness of PNI and SIRI in predicting the prognosis of patients with CRC.

We retrospectively gathered data from 470 CRC patients who underwent feasible radical surgery at Xinjiang Cancer Hospital. The optimal cut-off values for SIRI and PNI, along with their predictive power for survival, were determined through area under the receiver operating characteristic curve using time-dependent receiver operating characteristic analysis. The Kaplan-Meier method and log-rank test were applied to assess prognostic impact, and a multifactorial Cox proportional hazards model was employed for analysis. Additionally, a new model, PSIRI, was developed and assessed for its survival prediction capability.

The optimal cutoff values for PNI and SIRI were determined to be 47.80 and 1.38, respectively. Based on these values, patients were categorized into high PNI and low PNI groups, as well as high SIRI and low SIRI groups. Significant differences in age, T stage, neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) subgroups were observed between the PNI groups in the baseline profile. In the SIRI group, notable differences were found in gender, T stage, nerve invasion, intravascular tumor emboli, NLR, MLR, and PLR subgroups. Both low PNI and high SIRI were identified as independent risk factors for poor prognosis in CRC patients. When combined into the PSIRI model, it was shown that patients with a PSIRI ≤ 1 had a higher risk of death compared to those with a PSIRI of 2.

We assessed the impact of PNI and SIRI on the prognostic survival of CRC patients and developed a new model, PSIRI. This model demonstrated superior predictive accuracy, with a concordance index of 0.767.

The debate regarding the two possible roles of lymphadenectomy in surgical oncology, prognostic or therapeutic, is still ongoing. Furthermore, the use of lymphadenectomy as a proxy for the quality of the surgical procedure is another feature of discussion. Nevertheless, this reckoning depends on patient conditions, aggressiveness of the tumor, the surgeon, and the pathologist, and then it is not an absolute surrogate for the surgical quality. The international guidelines recommend a minimum of 12 lymph nodes harvested for pathological examination in colorectal cancer (CRC) surgery. There is a growing literature on reporting better survival when the lymph node yield is high, even when these nodes are negative for malignancy. On the other hand, there are studies reporting no survival benefit with high lymph node yield in stage I-II of CRC. Herein we review the roles of the lymphadenectomy in CRC, and discuss the results of studies on lymph node harvesting.

Colorectal cancer (CRC) is a major public health concern and identifying prognostic molecular biomarkers can help stratify patients based on risk profiles, thus enabling personalized medicine. Epitranscriptomic modifications play a relevant role in controlling gene expression, N6-methyladenosine (m6A) regulators play crucial roles in cancer progression, but their clinical significance in CRC cancer has thus far not been elucidated. Thus, we aimed to examine by immunohistochemical techniques and RT-qPCR, protein levels and RNAs expression of m6A writers (METTL3, WTAP) and eraser (FTO) in a cohort of 10 patients affected by CRC. The patients were followed for 5 years and values of METTL3, WTAP and FTO RNAs in alive vs dead patients were compared. Proteins expression and RNAs expression had a different trend, METTL3, WTAP and FTO proteins' expression showed an increasing trend from non-cancerous adjacent (N) tissue vs carcinoma (CA) tissue G1 stage, and then a decreasing trend from G1 to G2 and G3 stages. The most marked increase was observed in WTAP that, from a 40% of protein expression positivity in N tissue raised to the 81% of positivity in G1 stage K tissue. RNAs expression of METTL3, WTAP and FTO genes in N tissue vs G1 stage CA tissue was significantly different, the analysis and comparison of RNAs values in patient alive after 5 years (0.58±0.04) vs patients dead after 5 years (1.69±0.29) showed that only WTAP values resulted significantly high in dead patients. The fact that WTAP protein expression levels lower while WTAP RNA expression remains high, lets us hypothesize a sort of inhibition of protein expression, but further studies are needed to clarify the mechanism. Although the results suggest a relationship between biological meaning and prognostic utility of WTAP, this prognostic utility must be confirmed by further studies on a larger sample.

Lymphovascular invasion (LVI) is an important prognosticator in rectal cancer (RC). We aimed to determine predictors for LVI in RC and incorporate them into a predictive risk score (PRS).

Case-control analysis of predictors of LVI in RC using data from a national database (2010-2019). Main outcome was LVI in RC and its predictors. Odds ratios of significant independent predictors of LVI were incorporated into a PRS.

55,178 patients were included (60.9% male; mean age: 61.3 years). LVI was detected in 10,446 (18.9%). Independent predictors were carcinomas that were signet-ring cell (OR: 1.98, p < 0.001), moderately differentiated (OR: 1.58, p < 0.001), poorly differentiated (OR: 3.9, p < 0.001), or undifferentiated carcinomas (OR: 4.1, p < 0.001), cN1 (OR: 1.21, p < 0.001), and cN2 (OR: 1.49, p < 0.001), stage and incorporated into a PRS (0-8). Incidence of LVI was 16.3% in the low-risk group, 27.8% in the intermediate-risk group, and 40.5% in the high-risk group (p < 0.001). The PPV of the score was 40.5%, NPV was 83.7%, accuracy was 82.4%, and specificity was 97.9%.

High-grade adenocarcinomas, signet-ring cell carcinomas, and lymph node involvement in clinical assessment were independently associated with LVI in RC. Incorporation of these predictors into a PRS conferred high specificity and good accuracy.

The CDK4/6 inhibitor Ribociclib has shown limited efficacy as a monotherapy in colorectal cancer (CRC). However, combining Ribociclib with targeted therapies could present a viable strategy for treating CRC. This study evaluated the combination of Ribociclib and the PI3K inhibitor Alpelisib across four distinct cell lines representing different mutational statuses (PIK3CA/KRAS wild-type, KRAS-mutated, PIK3CA-mutated, and PIK3CA/KRAS-mutated). We analyzed the drugs' impact on key proteins involved in the PI3K pathway, cell cycle regulation, and apoptosis. The combination of Alpelisib and Ribociclib demonstrated a synergistic anti-proliferative effect across all cell lines, leading to a simultaneous decrease in pRB, pAKT, and p-S6 levels, and a more comprehensive suppression of the PI3K/AKT/mTOR pathway. Additionally, there was an upregulation of the apoptotic marker, p-BCL2, in cells treated with the combination compared to controls. In vivo studies using Caco-2, LS1034, and SNUC4 xenografts revealed a significant reduction in tumour growth with the combination therapy compared to single-agent treatments. These findings suggest that combining Alpelisib and Ribociclib could be a promising therapeutic approach for CRC, warranting further clinical exploration.

Several studies have observed that some stage III colorectal cancer (CRC) patients cannot benefit from standard adjuvant chemotherapy. However, there is no unified screening standard to date.

Consecutive patients with pathologically confirmed colon adenocarcinoma treated in 3 centers between January 2016 and December 2018 were included. Patients were divided into four groups according to different stages and positive paracolic lymph-node ratio (P-LNR) [Cohort 1: pT1-3N0M0, Cohort 2: pT1-3N + (P-LNR ≤ 0.15)M0, Cohort 3: pT4N0M0, Cohort 4: stage III patients except for pT1-3N + (P-LNR ≤ 0.15)M0], and further overall survival was compared by Kaplan-Meier method. The univariate and multivariate analyses were employed for cox proportional hazards model.

We retrospectively reviewed 5581 consecutive CRC patients with, and 2861 eligible patients were enrolled for further analysis. The optimal cut-off value of P-LNR in our study was 0.15. There was no significant difference in OS (91.36 vs. 93.74%) and DFS (87.65 vs. 90.96%) between stage III patients with pT1-3N + (P-LNR ≤ 0.15)M0 and those with pT1-3N0M0. Further analysis demonstrated that CRC patients with pT1-3N + (P-LNR ≤ 0.15)M0 were less likely to benefit from 8 cycles of CAPOX or FOLFOX chemotherapy and suffered fewer adverse events from declining chemotherapy. Comparing with 0-4 cycles versus 8 cycles, the overall survival rates were 91.35 versus 90.19% (P = 0.79), and with a DFS of 87.50 versus 88.24% (P = 0.49), the duration of adjuvant chemotherapy was not an independent risk factor for patients with pT1-3N + (P-LNR ≤ 0.15)M0 (HR: 0.70, 95% CI 0.90-1.30, P = 0.42).

The concept of P-LNR we proposed might have a high clinical application value and accurately enable clinicians to screen out specific CRC patients who decline or prefer limited chemotherapy.

The clinical trial registration number: ChiCTR2300076883.

The current pathological and physiological evaluation system for colorectal cancer (CRC) is limited; thus, effective biological targets to diagnose and treat this disease are urgently needed. In this study, we used qRT-PCR for detecting mRNA levels of genes. The levels of protein were identified by western blot, immunohistochemistry, and immunofluorescence assays. In addition, functional experiments were used to evaluate the role of cytoskeleton associated protein (CKAP) 2 in CRC cells and human umbilical vein endothelial cells (HUVECs). Bioinformatics analysis was employed to predict the binding relationship of CKAP2 and TFDP1, which was confirmed through dual luciferase reporter assay and immunoprecipitation assay. Furthermore, we injected human colorectal carcinoma HCT116 cells into mice flanks, and we injected Luciferase-labeled HCT116 cells into mice tail vein. HE staining was used to detect tumor nodules. As a result, high CKAP2 expression was found in CRC cells and tissues. CKAP2 silencing reduced CRC cell migration, invasion, proliferation, and epithelial-mesenchymal transition. Moreover, CKAP2 expression was positively associated with M2 macrophage levels. CKAP2 promoted protein expression of CD86, CD206, IL-1β, and CCL17. Moreover, CKAP2 promoted the proliferation of HUVECs and angiogenesis via affecting the tumor microenvironment (TME). We also found that CKAP2 could interact with TFDP1. The inhibitory impacts of TFDP1 downregulation on CRC cell' proliferation, migration, and invasion were reversed via CKAP2 overexpression. In vivo silencing of CKAP2 repressed tumor growth and metastasis. Overall, CKAP2 was positively regulated by TFDP1, which promoted tumorigenesis and metastasis in CRC.

To evaluate the influence of MMR complex protein immunoexpression on disease-free survival in oropharyngeal SCC treated non-surgically.

85 cases of oropharyngeal SCC diagnosed and treated at the Ceará Cancer Institute were surveyed, from which clinical-pathological data and paraffin blocks of incisional biopsies were retrieved for immunohistochemical reaction for MSH2, MSH6, PMS2, MLH1 and p16. Disease-free survival was calculated and Kruskal-Wallis and Friedman/Dunn tests, chi-square and Fisher's exact, Log-Rank Mantel Cox and Cox regression were performed.

In p16- tumors, loss of MSH2 expression was associated with shorter disease-free survival (p = 0.035) and mean MSH6 expression was significantly higher than MSH2 (p = 0.001). Loss of MSH2 expression in p16 + tumors was associated with longer disease-free survival compared to p16- tumors. Imbalance in the MSH6/MSH2 ratio in p16 + tumors was associated with longer survival compared to p16- tumors. MLH1/PMS2 imbalance was significantly higher in p16 + with recurrence (p = 0.003). Low MSH2 immunoexpression increased the risk of relapse by 9.10 times (CI95% 1.99 to 83.06).

Microsatellite instability in oropharyngeal SCC is demonstrated by the association between loss of protein expression and its heterodimer imbalance with disease-free survival. It was demonstrated that the imbalance of the MMR complex can consequently lead to resistance to treatment and a decrease in disease-free survival in p16 + oropharyngeal SCC tumors.

Colorectal cancer (CRC) lymph node metastasis (LNM) is a crucial factor affecting the prognosis and treatment outcomes of CRC patients. It has been confirmed that altered glycosylation is a key event during CRC lymphatic metastases. Sialylation is one of the most significant glycosylation alterations in tumors. However, the predictive role of sialylation and sialylated protein in CRC remains elusive, especially in CRC-LNM. In this study, we explored and identified 1102 sialylated glycoproteins in CRC-LNM using metabolic labeling strategy and proteomics analysis. Combined with comprehensive analysis with bioinformatics and machine learning algorithms, we screened 25 prognostic sialylation-related genes (SRGs) to construct a new molecular phenotype (LRSRGs-Phenotype) and a prognostic SRG signature (LRSRGs-related Gene Signature) in CRC. Then, we further confirmed that patients in different phenotypes had different prognosis, molecular biological characteristics, immune cell infiltration and could be closely linked to three previously reported immune phenotypes: immune-excluded (Phenotype A), immune-desert (Phenotype B), and immune-inflamed (Phenotype C). Besides, we evaluated and validated the LRSRGs-related gene (ACADM, EHD4, FLOT1, GPC1, GSR, LRRC8A, NGFR, SDHB, and SEC61G) signature and found the risk score was an independent risk factor for CRC prognosis. CRC patients in different risk groups had different somatic mutation, tumor microenvironment and immunotherapy response. Finally, we also identified the potential therapeutic agents for CRC patients in different risk groups. In conclusion, we explored the key sialylated glycoproteins, which may play a key role in tumor LNM and clinical outcomes. And constructed the LRSRGs-phenotype and signature with prognostic and therapeutic predictive value in CRC, hoping to provide reliable scientific basis for future treatments in CRC patients.

To evaluate the influence of MMR proteins on clinicopathological characteristics and prognosis of salivary gland adenoid cystic carcinoma (ACC).

The solid pattern of ACC showed lower expression for MSH2 (p = 0.039). Significant imbalance in MSH2/MSH6 immunostaining was observed in all histological patterns (p < 0.001), and imbalance in PMS2/MLH1 immunostaining was observed in the cribriform pattern (p = 0.011). The presence of capsule was associated with high expression of MSH6 (p = 0.019), MLH1 (p = 0.045) and PMS2 (p = 0.009). The absence of cribriform pattern (p = 0.002) and capsule pattern (p = 0.025), as well as low expression for MSH6 (p = 0.006) and PMS2 (p = 0.037) were associated with lower overall survival. In multivariate analysis, loss of MSH2 (p = 0.039) and MLH1 (p = 0.017) were significantly associated with worse overall survival.

Twenty-four ACC were clinical-pathologically evaluated and we perform immunohistochemistry for MSH2, MSH6, PMS2 and MLH1. Percentage counting of positive cells was performed in 10 fields of each histological pattern (cribriform, tubular and solid) and the averages of the 30 fields were considered for evaluation with other clinical-pathological variables (Kruskal-Wallis/Dunn, Friedman/Dunn, chi-square, Log-Rank Mantel-Cox tests and Cox regression; SPSS v20.0, p < 0.05).

Salivary glands' ACC shows imbalance of the MMR complex and loss of expression of its components is associated with the overall survival of these patients.

Colorectal cancer (CRC) is a significant global health concern. Prognostication of CRC traditionally relies on the Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC) TNM staging classifications, yet clinical outcomes often vary independently of stage. Despite similarities, rectal and colon cancers are distinct in their diagnostic methodologies and treatments, with MRI and CT scans primarily used for staging rectal and colon cancers, respectively. This paper examines the challenges in accurately assessing prognostic factors of colon cancer such as primary tumor extramural extension, retroperitoneal surgical margin (RSM) involvement, extramural vessel invasion (EMVI), and lymph node metastases through preoperative CT and MRI. It highlights the importance of these factors in risk stratification, treatment decisions, and surgical planning for colon cancer patients. Advancements in imaging techniques are crucial for improving clinical management and optimizing patient outcomes, underscoring the necessity for ongoing research to refine diagnostic methods and incorporate novel findings into practice.

Early screening is crucial in reducing the mortality of colorectal cancer (CRC). Current screening methods, including fecal occult blood tests (FOBT) and colonoscopy, are primarily limited by low patient compliance and the invasive nature of the procedures. Several advanced imaging techniques such as computed tomography (CT) and histological imaging have been integrated with artificial intelligence (AI) to enhance the detection of CRC. There are still limitations because of the challenges associated with image acquisition and the cost. Kidney, ureter, and bladder (KUB) radiograph which is inexpensive and widely used for abdominal assessments in emergency settings and shows potential for detecting CRC when enhanced using advanced techniques. This study aimed to develop a deep learning model (DLM) to detect CRC using KUB radiographs. This retrospective study was conducted using data from the Tri-Service General Hospital (TSGH) between January 2011 and December 2020, including patients with at least one KUB radiograph. Patients were divided into development (n = 28,055), tuning (n = 11,234), and internal validation (n = 16,875) sets. An additional 15,876 patients were collected from a community hospital as the external validation set. A 121-layer DenseNet convolutional network was trained to classify KUB images for CRC detection. The model performance was evaluated using receiver operating characteristic curves, with sensitivity, specificity, and area under the curve (AUC) as metrics. The AUC, sensitivity, and specificity of the DLM in the internal and external validation sets achieved 0.738, 61.3%, and 74.4%, as well as 0.656, 47.7%, and 72.9%, respectively. The model performed better for high-grade CRC, with AUCs of 0.744 and 0.674 in the internal and external sets, respectively. Stratified analysis showed superior performance in females aged 55-64 with high-grade cancers. AI-positive predictions were associated with a higher long-term risk of all-cause mortality in both validation cohorts. AI-enhanced KUB X-ray analysis can enhance CRC screening coverage and effectiveness, providing a cost-effective alternative to traditional methods. Further prospective studies are necessary to validate these findings and fully integrate this technology into clinical practice.

The convergence of the economic crisis, COVID-19 pandemic, and Beirut Blast has precipitated unprecedented challenges for the healthcare system in Lebanon, particularly for cancer patients. Amidst these crises, our study evaluates its contribution to a concerning trend of operating on more late-stage and complex colorectal cancer (CRC) cases.

We included 155 patients operated for CRC between 2017 and 2023. Patients age; sex; operation type (emergency or elective); tumor size, grade, and location; tumour, node, metastasis stage; lymphatic, vascular and perineural invasions; American Society of Anesthesiologists (ASA) score, presentation and previous history, and complications were examined.

Surgical outcomes remained relatively consistent before and after the crisis. However, there was a notable increase, with patients being 3.59 times more likely to undergo resection of adjacent organs in metastatic disease post-crisis. Patient characteristics also exhibited notable shifts, with a 9.60-fold increase in the likelihood of having an ASA score of at least 2 after the crisis. Additionally, there was a 5.36-fold decrease in the odds of patients undergoing a colonoscopy before their diagnostic one post-crisis. Preoperative carcinoembryonic antigen levels were significantly elevated post-crisis compared to pre-crisis levels. Pathological findings revealed increased odds of perineural, vascular, and lymphatic invasion post-crisis. Additionally, there was a notable increase in the likelihood of hepatic synchronous metastases post-crisis. Furthermore, a trend to operate on complicated diseases was noted with an increased number of colostomies.

The economic crisis in Lebanon has profoundly affected early intervention and comprehensive treatment for CRC patients, resulting in a concerning rise in late-stage cases requiring surgical intervention.

The study explored the prognostic value of caudal-type homeobox transcription factor 2 (CDX2) in stage II and III gastric cancer.

This study evaluated the expression level of CDX2 in gastric cancer in a hospital cohort (n=197) using immunohistochemistry. According to a semiquantitative score used to determine CDX2 expression, the cases were divided into a low CDX2 group (116 cases) and a high CDX2 group (81 cases). The RNA-seq expression data from 291 patients with stage II and III gastric cancer from The Cancer Genome Atlas (TCGA) cohort were used to verify the immunohistochemistry results. Based on the median CDX2 expression value, the TCGA patients were divided into a low CDX2 group (145 cases) and a high CDX2 group (146 cases). The relationships among CDX2 expression and clinicopathological features were determined using the Chi-square test. Cox proportional hazards regression models were applied to estimate the independent prognostic factors. The probability of survival was determined using the Kaplan-Meier method and Log rank tests.

Based on the Cox multivariate analysis, CDX2 was the independent prognostic factor in the hospital and TCGA cohorts. In the hospital cohort, CDX2 expression was associated with an improved DFS (hazard ratio [HR] = 0.4076, 95% CI, 0.2675-0.6210, P = 0.0001) and OS (HR = 0.4183, 95% CI, 0.2744-0.6375, P = 0.0002). In the TCGA cohort, CDX2 expression also was associated with an improved DFS (HR = 0.5948, 95% CI, 0.4153-0.8521, P = 0.0054) and OS (HR = 0.5976, 95% CI, 0.4172-0.8561, P = 0.0058). Furthermore, the CDX2 expression level was correlated with an improved DFS (P = 0.0025) and OS (P = 0.0015) using the Kaplan-Meier Plotter database for gastric cancer.

CDX2 is a potential prognostic biomarker for stage II and III gastric cancer. In addition, CDX2 positive cancer patients are more likely to have resectable tumors and exhibit better survival rates.

Tumor tissue collections are used to uncover pathways associated with disease outcomes that can also serve as targets for cancer treatment, ideally by comparing the molecular properties of cancer tissues to matching normal tissues. The quality of such collections determines the value of the data and information generated from their analyses including expression and modifications of nucleic acids and proteins. These biomolecules are dysregulated upon ischemia and decompose once the living cells start to decay into inanimate matter. Therefore, ischemia time before final tissue preservation is the most important determinant of the quality of a tissue collection. Here we show the impact of ischemia time on tumor and matching adjacent normal tissue samples for mRNAs in 1664, proteins in 1818, and phosphosites in 1800 cases (tumor and matching normal samples) of four solid tumor types (CRC, HCC, LUAD, and LUSC NSCLC subtypes). In CRC, ischemia times exceeding 15 min impacted 12.5% (mRNA), 25% (protein), and 50% (phosphosites) of differentially expressed molecules in tumor versus normal tissues. This hypoxia- and decay-induced dysregulation increased with longer ischemia times and was observed across tumor types. Interestingly, the proteomics analysis revealed that specimen ischemia time above 15 min is mostly associated with a dysregulation of proteins in the immune-response pathway and less so with metabolic processes. We conclude that ischemia time is a crucial quality parameter for tissue collections used for target discovery and validation in cancer research.

Colorectal carcinoma is a leading cause of cancer morbidity and mortality globally. Its management includes the use of targeted therapy which require assessment for biomarkers to choose eligible patients. KRAS and BRAF mutations are biomarkers predictive of response to anti-EGFR therapy. This study aimed at determining the frequency of BRAF V600E and KRAS exon 2,3,4 mutations in colorectal carcinoma patients at the Aga Khan University Hospital Nairobi, Kenya.

Study participants were patients who had colectomy for colorectal carcinoma. They were identified from the laboratory information system. The patients age, gender and tumor location were determined from the medical records. The histological diagnosis, pathological tumor and nodal stage were confirmed by examining hematoxylin and eosin-stained slides prepared from the colectomy specimen. DNA was extracted from the specimens using Qiagen QIAamp DNA FFPE Tissue Kit and PCR performed using EntroGen KRAS/BRAF mutation analysis kit following manufacturer's protocol.

One hundred fourteen patients were enrolled. Colorectal carcinoma was significantly more common in males than females. The mean age at diagnosis was 58 years. Majority of the tumors were in the right colon, were of pathological tumor stage T3 and had nodal involvement. Forty six percent (46%) of the cases had KRAS mutations while 5.3% had BRAF V600E mutation. KRAS mutation was associated with a high pathological tumor stage and nodal involvement.

Colorectal carcinoma in our patients is more common in males and tend to occur at a younger age. The patients tend to have a high tumor pathological stage and nodal involvement at diagnosis. The high frequency of KRAS exon 2,3,4 mutation and low frequency of BRAF V600E mutations is similar to what has been reported in literature.

Crohn's disease (CD) exhibits variability in colorectal cancer (CRC) incidence and prognostic factors due to diverse clinical and behavioral characteristics, presenting inconsistencies between Western and Eastern patients.

This study compared clinical characteristics between CD patients with CRC from the US and Korean tertiary referral centers and defined the prognostic factors related to mortality.

Retrospective study.

We reviewed the electronic medical records of 236 adult CD patients with colorectal adenocarcinoma evaluated at Mayo Clinic Rochester, Florida, or Arizona (N = 200) and Asan Medical Center in Korea (N = 36) between January 1989 and August 2022.

Asan patients had a younger age, shorter CD duration, more colonic involvement (L2 plus L3), penetrating behavior, perianal fistula, and shorter biological treatment duration before CRC diagnosis than Mayo patients. Furthermore, despite significant differences in body mass index, smoking status, primary sclerosing cholangitis, immunomodulators, CRC diagnosis period, clinical presentation, CRC location, surgery, and some histopathological details between the two groups, overall survival was not statistically different (p value, 0.29, log-rank test). Advanced age (adjusted hazard ratio (aHR), 1.03 per year; 95% confidence interval (CI), 1.01-1.04; p value, <0.01), unresectable CRC (aHR, 5.02; 95% CI, 2.49-10.12; p value, <0.01), and advanced CRC stage (aHR, 1.45 per stage; 95% CI, 1.07-1.97; p value, 0.02) were significantly associated with increased risk of death. CD remission at CRC diagnosis (aHR, 0.26; 95% CI, 0.08-0.91; p value, 0.04), CRC diagnosis period of 2011-2022 (aHR relative to 1989-2000, 0.46; 95% CI, 0.25-0.87; p value, 0.02), and CRC diagnosis by surveillance (aHR, 0.56; 95% CI, 0.32-0.98; p value, 0.04) were significantly associated with decreased risk of death.

Notably, some clinical features of CD with CRC differed between Asan and Mayo patients; however, overall survival was not different. CD remission, CRC surveillance, and more recent diagnosis of CRC were associated with a reduced risk of death.

To explore the predictive value of dual-layer spectral detector CT (SDCT) quantitative parameters for determining differentiation grade, lymphovascular invasion (LVI) and perineural invasion (PNI) in colorectal adenocarcinoma (CRAC) patients.

A total of 106 eligible patients with CRAC were included in this study. Spectral parameters, including CT values at 40 and 100 keV, the effective atomic number (Zeff), the iodine concentration (IC), the slope of the spectral Hounsfield unit (HU) curve (λHU), and the normalized iodine concentration (NIC) in the arterial phase (AP) and venous phase (VP), were compared according to the differentiation grade and the status of LVI and PNI. The diagnostic accuracies of the quantitative parameters with statistical significance were determined via receiver operating characteristic (ROC) curves, and the area under the curve (AUC) was calculated.

There were 57 males and 49 females aged 43-86 (69 ± 10) years. The measured values of the spectral quantitative parameters of the CRAC were consistent within the observer (ICC range: 0.800-0.926). The 40 keV-AP, IC-AP, NIC-AP, 40 keV-VP, and IC-VP were significantly different among the different differentiation grades in the CRAC (P = 0.040, AUC = 0.673; P = 0.035, AUC = 0.684; P = 0.031, AUC = 0.639; P = 0.044, AUC = 0.663 and P = 0.035, AUC = 0.666, respectively). A statistically significant difference was observed in 40 keV-VP, 100 keV-VP, Zeff-VP, IC-VP, and λHU-VP between LVI-positive and LVI-negative patients (P = 0.003, AUC = 0.688; P = 0.015, AUC = 0.644; P = 0.001, AUC = 0.688; P = 0.001, AUC = 0.703 and P = 0.003, AUC = 0.677, respectively). There were no statistically significant differences in the values of the spectral parameters of the PNI state of patients with CRAC (P > 0.05).

The quantitative parameters of SDCT had good diagnostic efficacy in differentiating between different grades and statuses of LVI in patients with CRAC; however, SDCT did not have value for identifying the state of PNI.