Survival Of Colorectal Cancer Patients Research Articles

Identification of key lncRNAs associated with oxaliplatin resistance in colorectal cancer cells and isolated exosomes: From In-Silico prediction to In-Vitro validation.

One of the critical challenges in managing colorectal cancer (CRC) is the development of oxaliplatin (OXP) resistance. Long non-coding RNAs (lncRNAs) have a crucial role in CRC progression and chemotherapy resistance, with exosomal lncRNAs emerging as potential biomarkers. This study aimed to predict key lncRNAs involved in OXP-resistance using in-silico methods and validate them using RT-qPCR methods in CRC cells and their isolated exosomes. Two public datasets, GSE42387 and GSE119481, were downloaded from the GEO database to identify differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) associated with OXP-resistance in the HCT116 cell line. The analysis of GSE42387 revealed 210 DEGs, and GSE119481 identified 73 DEmiRNAs. A protein-protein interaction (PPI) network analysis of the DEGs identified 133 interconnected genes, from which the top ten genes with the highest degree scores were selected. By intersecting predicted miRNAs targeting these genes with the DEmiRNAs, 38 common miRNAs were found. Subsequently, 224 lncRNAs targeting these common miRNAs were predicted. LncRNA-miRNA-mRNA network were constructed and the top five lncRNAs with the highest degree scores were identified. Analysis using the Kaplan-Meier plotter database revealed that the key lncRNAs NEAT1, OIP5-AS1, and MALAT1 are significantly associated with the overall survival of CRC patients. To validate these lncRNAs, OXP-resistant HCT116 sub-cell line (HCT116/OXR) was developed by exposing parental HCT116 cells to gradually increasing concentrations of OXP. Exosomes derived from both HCT116 and HCT116/OXR cells were isolated and characterized utilizing dynamic light scattering (DLS), transmission electron microscopy (TEM), and Western blotting. RT-qPCR confirmed elevated levels of NEAT1, OIP5-AS1, and MALAT1 in HCT116/OXR cells and their exosomes compared to parental HCT116 cells and their exosomes. This study concludes that NEAT1, OIP5-AS1, and MALAT1 are associated with the OXP-resistance in CRC. The high levels of these lncRNAs in exosomes of resistant cells suggest their involvement in intercellular communication and resistance propagation. This positioning makes them promising biomarkers for OXP-resistance in CRC.

Evaluation of the prognostic effectiveness of liver metastasis volume by volumetric measurement in colorectal cancer.

Aim: To evaluate the relationship between liver metastasis volume and survival in colorectal cancer patients using the volumetric measurement method.Methods: 114 colorectal cancer patients with isolated liver metastases were included in the study. Liver tumor volume, total liver volume were calculated from the patients images at the time of diagnosis. Vitrea 7.14 imaging software was used for liver volume analysis and volume analysis of each metastasis.Results: Median overall survival(OS) in the group with tumor volume <42ml3 was 30.98months In the group with tumor volume ≥42ml3, median OS was 16.36months (p: 0.001). In patients who underwent metastasectomy, the median OS in the group with a tumor volume <42ml3 was 52.3months, the median OS in the group with a tumor volume ≥42ml3 was 22.2months. In patients who did not undergo metastasectomy, the median OS in the <42ml3 group was 20.23months, the median OS in the ≥42ml3 group was 15.63months.Conclusion: In our study, we found that liver metastasis volume was prognostic for OS. It is argued that tumor volume measurement by volumetric measurement is a widely used method in the decision for metastasectomy in liver metastatic colorectal cancer patients.

Bulk integrated single-cell-spatial transcriptomics reveals the impact of preoperative chemotherapy on cancer-associated fibroblasts and tumor cells in colorectal cancer, and construction of related predictive models using machine learning

BackgroundPreoperative chemotherapy (PC) is an important component of Colorectal cancer (CRC) treatment, but its effects on the biological functions of fibroblasts and epithelial cells in CRC are unclear. MethodsThis study utilized bulk, single-cell, and spatial transcriptomic sequencing data from 22 independent cohorts of CRC. Through bioinformatics analysis and in vitro experiments, the research investigated the impact of PC on fibroblast and epithelial cells in CRC. Subpopulations associated with PC and CRC prognosis were identified, and a predictive model was constructed using machine learning. ResultsPC significantly attenuated the pathways related to tumor progression in fibroblasts and epithelial cells. NOTCH3 + Fibroblast (NOTCH3 + Fib), TNNT1 + Epithelial (TNNT1 + Epi), and HSPA1A + Epithelial (HSPA1A + Epi) subpopulations were identified in the adjacent spatial region and were associated with poor prognosis in CRC. PC effectively diminished the presence of these subpopulations, concurrently inhibiting pathway activity and intercellular crosstalk. A risk signature model, named the Preoperative Chemotherapy Risk Signature Model (PCRSM), was constructed using machine learning. PCRSM emerged as an independent prognostic indicator for CRC, impacting both overall survival (OS) and recurrence-free survival (RFS), surpassing the performance of 89 previously published CRC risk signatures. Additionally, patients with a high PCRSM risk score showed sensitivity to fluorouracil-based adjuvant chemotherapy (FOLFOX) but resistance to single chemotherapy drugs (such as Bevacizumab and Oxaliplatin). Furthermore, this study predicted that patients with high PCRSM were resistant to anti-PD1therapy. ConclusionIn conclusion, this study identified three cell subpopulations (NOTCH3 + Fib, TNNT1 + Epi, and HSPA1A + Epi) associated with PC, which can be targeted to improve the prognosis of CRC patients. The PCRSM model shows promise in enhancing the survival and treatment of CRC patients.

Hypoxia-Associated GPNMB+ Macrophages Promote Malignant Progression of Colorectal Cancer and Its RelatedRisk Signature Are Powerful Predictive Tool for theTreatment of Colorectal Cancer Patients.

Colorectal cancer (CRC) is a highly malignant tumor with hypoxia being a crucial feature during its progression. This study utilized multiple independent CRC cohorts for bioinformatics analysis and in vitro experiments to investigate the role of hypoxia-related subgroups in CRC. Machine learning was employed to construct risk features associated with this subgroup and further explore its therapeutic value in CRC. The study identified the GPNMB+ Macrophage (GPNMB+ Macr) subgroup as most relevant to hypoxia. GPNMB+ Macr showed significantly higher infiltration in tumor tissues compared to non-tumor tissues, increasing with CRC stage. High infiltration of GPNMB+ Macr was associated with poor prognosis in terms of overall and recurrence-free survival in CRC patients. GPNMB+ Macrophages exhibit M2-like characteristics and have the ability to promote 5-FU resistance, proliferation, and metastasis of CRC cells. The study developed the Hypoxia-Related Macrophage Risk Score (HMRS), which not only served as an independent prognostic factor for CRC patients but also demonstrated robust prognostic performance compared to 84 previously published prognostic features. Patients with low HMRS were sensitive to fluorouracil, oxaliplatin (FOLFOX), and anti-PD-1 immunotherapy, while those with high HMRS showed resistance. Additionally, HMRS was identified as an independent prognostic factor in other digestive tract tumors (hepatocellular carcinoma, pancreatic cancer, esophageal cancer, and gastric cancer), indicating potential extrapolation to other tumor types. In conclusion, GPNMB+ Macr promotes the malignant progression of CRC, and HMRS serves as a powerful predictive tool for prognosis, chemotherapy, and immunotherapy in CRC patients, aiding in improving the quality of survival.

Sarcopenia Predicts Postoperative Complications and Survival of Colorectal Cancer Patients Undergoing Radical Surgery.

Aims/Background Previous literature has indicated that sarcopenia is related to poor outcomes after radical resection for colorectal cancer (CRC). However, its effect on the postoperative clinical outcomes of CRC remains controversial. This study aimed to elucidate the predictive value of sarcopenia for postoperative complications and survival in CRC patients. Methods This investigation retrospectively assessed the clinical data of 226 CRC patients who underwent radical resection at the Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University from January 2018 to December 2020. Sarcopenia was diagnosed according to the recommendations of the Asian Working Group for Sarcopenia in 2019, and patients were categorized into sarcopenia and non-sarcopenia groups. Multivariate and univariate analyses were employed to assess the risk factors for postoperative complications. The Kaplan-Meier method and survival curve were used to analyze postoperative survival time. Cox proportional hazards regression models were used to evaluate risk factors affecting the prognosis of CRC patients. Results This investigation included 226 patients, of which 68 were diagnosed with sarcopenia. Furthermore, it was revealed that sarcopenia was linked with older age (p < 0.001), low body mass index (p < 0.001), high prevalence of diabetes (p = 0.002), high cystatin level (p = 0.017), and low 3rd lumbar spine (L3) planar skeletal muscle index (p < 0.001), but was not related to the tumour stage or the gender. Moreover, sarcopenia was also correlated with increased occurrence of all postoperative complications (p = 0.050). The results of the multivariate analysis indicated that sarcopenia was an independent risk factor for postoperative complications (odds ratio (OR): 7.154; 95% confidence interval (CI): 2.261-22.633; p = 0.017). The Kaplan-Meier analysis revealed that sarcopenia patients had significantly lower 5-year disease-free survival (DFS) (48.5% vs 59.5%; log-rank p = 0.033) and 5-year overall survival (OS) (57.4% vs 77.2%; log-rank p < 0.001) rates. Sarcopenia was an independent risk factor for poor DFS (hazard ratio (HR) = 1.404; p = 0.016) and OS (HR = 1.290; p = 0.021). Conclusion In CRC patients undergoing radical surgery, sarcopenia is an independent risk factor for postoperative complications. Sarcopenia may be a predictive factor for the prognosis and survival of CRC patients undergoing radical resection.

Competing-Risk Nomogram for Predicting Cancer-Specific Survival in Multiple Primary Colorectal Cancer Patients after Surgery.

Cancer-specific survival (CSS) in multiple primary colorectal cancer (MPCC) patients is competitively affected by death from other causes. This study aimed to investigate CSS and associated risk factors by competing risk analysis in MPCC patients. The data of this study is from the SEER database. Using univariable and multivariable analysis of the competitive risk model to weaken the impact of competitive events, it explores the risk factors of CSS and develops a nomogram model. Then, the performance of the model is verified by the ROC curve, calibration curve, and DCA. The study encompasses a total of 8931 patients, with 6255 in the training cohort and 2676 in the validation cohort. Univariable and multivariable analyses showed that sex, Tumor Node Metastasis (TNM) stage, and tumor grade are independent risk factors for cancer-specific survival in MPCC patients. Based on the risk factors, we developed a diagram model to predict CSS. ROC curve, calibration curve, and DCA also show good results. In conclusion, a nomogram is developed that serves as a valuable tool for predicting CSS in MPCC patients, providing clinicians with crucial insights for personalized treatment planning.

The Impact of Preoperative and Postoperative Nutritional Interventions on Treatment Outcomes and Quality of Life in Colorectal Cancer Patients-A Comprehensive Review.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, with high morbidity and mortality rates. Nutritional status has emerged as a significant factor influencing the prognosis and survival of CRC patients. This comprehensive literature review examines the role of nutritional support in improving treatment outcomes, including the efficacy of interventions, patient quality of life (QoL), and the modulation of inflammatory responses. The findings suggest that tailored nutritional interventions improve clinical outcomes, enhance QoL, and reduce treatment-related complications, particularly by attenuating inflammation. Furthermore, the review highlights the cost-effectiveness of nutritional strategies and identifies key methods to enhance patient compliance with dietary recommendations. In conclusion, integrating nutritional support into CRC treatment plans is crucial for optimizing clinical management and improving patient well-being.

Overexpression of Osteopontin-a and Osteopontin-c Splice Variants Are Worse Prognostic Features in Colorectal Cancer

Background: Osteopontin (OPN) is a glycoprotein involved in various physiological and pathological processes, and its aberrant expression in cancer cells is closely linked to tumor progression. In colorectal cancer (CRC), OPN is overexpressed, but the roles of its splice variants (OPN-SVs), OPNa, OPNb, and OPNc, are not well understood. This study aimed to characterize the expression patterns of OPN-SVs and their potential diagnostic and prognostic implications in CRC using transcriptomic data deposited in TSVdb and TCGA. Methods: The expression patterns of each OPN-SV were analyzed using transcriptomic data deposited in TSVdb and TCGA, which were correlated to patient data available at cBioPortal. Results: Bioinformatic analysis revealed that OPNa, OPNb, and OPNc are overexpressed in CRC samples compared to non-tumor samples. Notably, OPNa and OPNc are overexpressed in CRC stages (II, III, and IV) compared to stage I. Higher levels of OPNa and OPNc transcripts are associated with worse overall survival (OS) and shorter progression-free survival (PFS) in CRC patients. Additionally, the expression of OPNa, OPNb, and OPNc is correlated with BRAFV600E mutations in CRC samples. Conclusions: These findings suggest that OPNa and OPNc, in particular, have potential as diagnostic and prognostic biomarkers, paving the way for their further evaluation in CRC diagnosis and prognosis.

Circulating tryptophan–kynurenine pathway metabolites are associated with all‐cause mortality among patients with stage I–III colorectal cancer

AbstractAlterations within the tryptophan–kynurenine metabolic pathway have been linked to the etiology of colorectal cancer (CRC), but the relevance of this pathway for prognostic outcomes in CRC patients needs further elucidation. Therefore, we investigated associations between circulating concentrations of tryptophan–kynurenine pathway metabolites and all‐cause mortality among CRC patients. This study utilizes data from 2102 stage I–III CRC patients participating in six prospective cohorts involved in the international FOCUS Consortium. Preoperative circulating concentrations of tryptophan, kynurenine, kynurenic acid (KA), 3‐hydroxykynurenine (HK), xanthurenic acid (XA), 3‐hydroxyanthranilic acid (HAA), anthranilic acid (AA), picolinic acid (PA), and quinolinic acid (QA) were measured by liquid chromatography–tandem mass spectrometry. Using Cox proportional hazards regression, we examined associations of above‐mentioned metabolites with all‐cause mortality, adjusted for potential confounders. During a median follow‐up of 3.2 years (interquartile range: 2.2–4.9), 290 patients (13.8%) deceased. Higher blood concentrations of tryptophan, XA, and PA were associated with a lower risk of all‐cause mortality (per doubling in concentrations: tryptophan: HR = 0.56; 95%CI:0.41,0.76, XA: HR = 0.74; 95%CI:0.64,0.85, PA: HR = 0.76; 95%CI:0.64,0.92), while higher concentrations of HK and QA were associated with an increased risk of death (per doubling in concentrations: HK: HR = 1.80; 95%CI:1.47,2.21, QA: HR = 1.31; 95%CI:1.05,1.63). A higher kynurenine‐to‐tryptophan ratio, a marker of cell‐mediated immune activation, was associated with an increased risk of death (per doubling: HR = 2.07; 95%CI:1.52,2.83). In conclusion, tryptophan–kynurenine pathway metabolites may be prognostic markers of survival in CRC patients.

A Novel Approach for Predicting the Survival of Colorectal Cancer Patients Using Machine Learning Techniques and Advanced Parameter Optimization Methods.

Colorectal cancer is one of the most prevalent forms of cancer and is associated with a high mortality rate. Additionally, an increasing number of adults under 50 are being diagnosed with the disease. This underscores the importance of leveraging modern technologies, such as artificial intelligence, for early diagnosis and treatment support. Eight classifiers were utilized in this research: Random Forest, XGBoost, CatBoost, LightGBM, Gradient Boosting, Extra Trees, the k-nearest neighbor algorithm (KNN), and decision trees. These algorithms were optimized using the frameworks Optuna, RayTune, and HyperOpt. This study was conducted on a public dataset from Brazil, containing information on tens of thousands of patients. The models developed in this study demonstrated high classification accuracy in predicting one-, three-, and five-year survival, as well as overall mortality and cancer-specific mortality. The CatBoost, LightGBM, Gradient Boosting, and Random Forest classifiers delivered the best performance, achieving an accuracy of approximately 80% across all the evaluated tasks. This research enabled the development of effective classification models that can be applied in clinical practice.

MiRNA expression affects survival in patients with obstructive sleep apnea and metastatic colorectal cancer

IntroductionThe relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs. MethodsThe expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients’ sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs. ResultsThe expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly. ConclusionsThis study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA.

Retrospective cohort study on the postoperative survival rate enhancement of patients with colorectal cancer using three traditional Chinese medicine formulations: evidence from 1,361 cases

Background: Prior studies have affirmed the safety and effectiveness of traditional Chinese medicine in treating colorectal cancer patients. However, definitive evidence regarding whether traditional Chinese medicine can significantly enhance the survival of colorectal cancer patients remains elusive. This study seeks to provide conclusive insights by examining the postoperative administration of Xihuang capsules, Pingxiao capsules, and Zilongjin tablets and its impact on the 5-year overall survival (OS) and disease-free survival (DFS) rates among colorectal cancer patients. Methods: A retrospective study was conducted, involving 1,361 patients selected from the medical center. This retrospective study was carried out at a medical center in Tianjin, China. We assessed differences in postoperative OS and DFS between the control group and the medication group using Kaplan–Meier survival analysis and Cox proportional hazards modeling. Additionally, propensity score matching was used to mitigate imbalances in baseline characteristics among patients. Results: Before propensity score matching, Xihuang capsules could prolong the 5-year OS (79.9% vs. 81.4%, P = 0.0480) and 5-year DFS (74.9% vs. 79.5%, P = 0.0046) of patients after surgery. Similar conclusions were obtained after propensity score matching: OS (74.8% vs. 78.3%, P = 0.0084), DFS (72.7% vs. 78.9%, P = 0.008). Patients taking Pingxiao capsules showed improved 5-year OS (77.2% vs. 84.0%, P = 0.0383) and 5-year DFS (69.9% vs. 80.0%, P = 0.0157) after propensity score matching. Patients taking Zilongjin tablets showed improvement in the 2-year OS (84.2% vs. 93.1%, P = 0.0390) and 1-year DFS (88.2% vs. 92.0%, P = 0.0320) after propensity score matching. Conclusion: Xihuang capsules and Pingxiao capsules significantly improved the 5-year OS and DFS of patients with colorectal cancer after surgery. Zilongjin tablets showed improvement in the 2-year OS and 1-year DFS after surgery for patients.

Prognostic Impact of Para-Aortic Lymph Node Dissection in Colorectal Cancer Patients Suspected of Para-Aortic Lymph Node Metastasis: A Retrospective Cohort Study

BackgroundPara-aortic lymph node metastasis (PALNM) is a rare occurrence in colorectal cancer (CRC), and the high risk of radical lymphadenectomy leads to persistent debate about the best treatment strategy. This study aims to evaluate the predictor for PALNM and the clinical value of para-aortic lymph node dissection (PALND) in CRC patients with radiologically suspected synchronous PALNM. MethodsPatients who has synchronous radiologically suspected PALNM and underwent primary tumor resection were included. Logistic regression and receiver operating characteristic curve analysis were used to assess the predictive value of lymph node short axis in preoperative CT, identifying the optimal cut-off value. Propensity score matching and Cox regression explored factors affecting overall and disease-free survival, while Kaplan-Meier curves and decision tree models identified patient characteristics suitable for synchronous paraaortic lymph node dissection. ResultsA total of 578 patients were enrolled, and 125 patients received synchronous PALND. We found that simultaneous PALND significantly improved overall survival (HR, 0.56; 95% CI, 0.35-0.91; P = .019) in multivariate analysis, while disease-free survival showed no significant difference (P = .41). The short axis diameter of PALN on preoperative CT is a crucial predictor of PALNM (P < .001, AUC = 0.759) with a threshold of > 7 mm. N-stage and distant metastasis were included as independent predictors in the diagnostic model to enhance accuracy. A larger short axis diameter of PALN correlated with advanced tumor stage and poorer prognosis. Subgroup analysis revealed that PALND offers survival benefits for colorectal cancer patients at all stages with a short axis diameter >10mm on preoperative CT (P = .037) and for stage III patients with a diameter between 7 to10 mm (P < .001, AUC = 0.810). ConclusionSynchronous PALND can improve overall survival in CRC patients with suspected PALNM, with the maximum short axis diameter of PALN serving as a key criterion for selecting patients for surgery.

Prognostic stratification of patients with pT4bN0M0 colorectal cancer following multivisceral resection: a multi-institutional case series analysis.

Colorectal cancer (CRC) patients with stage pT4b are a complex group as they show differences in tumor-infiltrated organs. Patients with the same stage often exhibit differences in prognosis after multivisceral resection (MVR). Thus far, some important prognostic factors have not been thoroughly investigated. Here, we identified the prognostic factors influencing CRC patients at the pT4bN0M0 stage to stratify the prognostic differences among patients. A retrospective analysis was conducted on patients diagnosed with locally advanced CRC and who underwent MVR at three medical institutions from January 2010 to December 2021. The prognostic factors affecting the survival of CRC patients at pT4bN0M0 stage were identified by multivariate Cox proportional hazard models. We then classified the prognosis into different grades on the basis of these independent prognostic factors. We enrolled 690 patients with locally advanced CRC who underwent MVR; of these, 172 patients with pT4bN0M0 were finally included. Patients with digestive system [overall survival (OS): hazard ratio (HR)=0.441; 95% confidence interval (CI)=0.217-0.900; P =0.024; disease-free survival (DFS): HR=0.416; 95% CI=0.218-0.796; P =0.008) or genitourinary system invasion (OS: HR=0.405; 95% CI=0.193-0.851; P =0.017; DFS: HR=0.505; 95% CI=0.267-0.954; P =0.035) exhibited significantly better OS and DFS as compared to those with gynecological system invasion, while the OS and DFS were similar between the digestive system and genitourinary system invasion groups (OS: HR=0.941; 95% CI=0.434-2.042; P =0.878; DFS: HR=1.211; 95% CI=0.611-2.403; P =0.583). Multivariate analysis showed that age (OS: HR=2.121; 95% CI=1.157-3.886; P =0.015; DFS: HR=1.869; 95% CI=1.116-3.131; P =0.017) and type of organs invaded by CRC (OS: HR=3.107; 95% CI=1.121-8.609; P =0.029; DFS: HR=2.827; 95% CI=1.142-6.997; P =0.025) were the independent prognostic factors that influenced the OS and DFS of CRC patients with pT4bN0M0 disease. The OS and DFS of patients showing invasion of the gynecological system group were significantly worse ( P =0.004 and P =0.003, respectively) than those of patients with invasion of the nongynecological system group. On the basis of the above-mentioned two independent prognostic factors, patients were assigned to high-risk, medium-risk, and low-risk groups. Subgroup analysis showed that the OS and DFS of the medium-risk and high-risk groups were significantly worse ( P =0.001 and P =0.001, respectively) than those of the low-risk group. Patients with pT4bN0M0 CRC show significant differences in their prognosis. The type of organs invaded by CRC is a valuable indicator for prognostic stratification of CRC patients with pT4bN0M0.

Cure models, survival probabilities, and solid organ transplantation for patients with colorectal cancer

A previous cancer diagnosis can preclude patients from consideration for solid organ transplantation. Statistical models may improve candidate selection. We fitted statistical cure models and estimated 5-year cancer-specific survival (5yCSS) for colorectal cancer patients in the United States using registry data. The median cure probability at cancer diagnosis for patients in the general population was 0.67. Among 956 colorectal cancer patients who underwent solid organ transplantation, the median time since diagnosis was 6.3 years and the median 5yCSS at transplantation was 0.96. Patients with a 5yCSS below 0.90 had increased posttransplant cancer-specific mortality (hazard ratio 3.31, 95% CI 1.52-7.21). Compared with recently published guidelines, our models suggested shorter wait times for some groups of colorectal cancer patients (eg, stage IIA cancers) and longer wait times for others (stages IIB, IIIB, IIIC, IV). In conclusion, colorectal cancer patients undergoing solid organ transplantation had excellent prognoses, reflecting selection incorporating existing guidelines and clinical judgment. Nonetheless, 5yCSS probabilities estimated from cure models offer additional prognostic information for patients considered for transplantation and identify situations where current guidelines might be revised. We developed a web-based tool for clinicians to calculate 5yCSS probabilities for use in transplant evaluation for individual colorectal cancer patients (https://dceg.cancer.gov/tools/risk-assessment/calculator-of-colorectal-cancer-survival-probability).

Integrative analysis of the immunological significances of guanylate binding protein family genes in microsatellite stability colorectal cancer

BackgroundMicrosatellite stability (MSS) colorectal cancer (CRC) has poor sensitivity to immunotherapy and its underlying mechanisms are still unclear. Guanylate binding proteins (GBPs) are a family of GTPase involving innate immune responses by providing defense against invading microbes and pathogens. However, the immunological significances of GBPs in MSS CRC remain unknown. MethodsWe utilized bioinformatic tools to comprehensively analysis the expression pattern, clinical relevance, prognostic value, biological function, and immunoregulation effect of distinct GBP members in MSS CRC. ResultsThe expression of all seven GBPs in MSS samples are remarkably decreased compared to microsatellite instability-high (MSI-H) samples. Among them, GBP1/2/4/5 are obviously correlated with distant metastasis status. High expression of GBP1/4/5/6 was remarkably related to favorable overall survival (OS) and progression-free survival (PFS) in CRC patients with MSS tumor. Subsequent enrichment analysis revealed that Interferon-gamma (IFN-γ) and NOD-like receptor signaling are the most relevant functions. Besides, the expression patterns of GBPs are remarkably associated with several tumor infiltrated immune cells (e.g. regulatory T cells, CD4+ T cells, and macrophages) and diverse immunoregulatory molecules (e.g. immune checkpoint biomarkers (ICBs) and major histocompatibility complex (MHC) molecules). Moreover, high GBP1/2/4/5 expression predicted better immunotherapy responsiveness in immunotherapy cohorts. ConclusionThese findings might provide novel insights for the identification of therapeutic targets and potential prognostic biomarkers of GBP family in CRC with MSS samples.

Silencing GDI2 inhibits proliferation, migration and invasion of colorectal cancer through activation of p53 signaling pathway

ObjectiveTo investigate the effect of silencing GDP dissociation inhibitor 2 (GDI2) on colorectal cancer development and possible mechanisms based on transcriptomic analysis. MethodsThe differences in the expression levels of GDI2 in normal colorectal tissues and tumor tissues of colorectal cancer (CRC) patients were detected. The correlation of GDI2 expression levels with survival and clinical characteristics of CRC patients was analyzed. The effects of GDI2 expression levels on the biological functions of CRC cells were examined by CCK-8 assay, plate clone formation assay, wound healing assay, and Transwell assay. The effect of GDI2 on the proliferation and growth of xenograft tumors was investigated by a xenograft tumor model of CRC in nude mice. Based on transcriptomics, we explored the possible mechanisms and associated pathways of the effect of silencing GDI2 on CRC cells. Cellular experiments and Western blot assays were performed to verify the potential mechanisms and related pathway of GDI2 action on CRC. ResultsThe expression levels of GDI2 in CRC tissues and cells were higher than those in normal tissues and cells. The expression level of GDI2 correlated with clinical characteristics such as lymphatic metastasis, tumor stage, tumor volume, and lymphocyte count. Silencing of GDI2 reduced the proliferative activity and migration and invasion ability of CRC cells, as well as inhibited the proliferation of CRC xenograft tumors. The differentially expressed genes were significantly enriched in biological processes such as cell cycle arrest and the p53 signaling pathway after GDI2 silencing. The percentage of G0/G1 phase cells in CRC cells was increased after silencing GDI2 as verified by flow cytometry. RAB5A was highly associated with the p53 pathway and could interact with TP53 via the ZFYVE20 protein. The mutual binding between GDI2 protein and RAB5A protein was verified by immunoprecipitation assay. Silencing GDI2 while overexpressing RAB5A reversed the reduced proliferation, migration, and invasion ability as well as cell cycle arrest of CRC cells. Meanwhile, the addition of p53 signaling pathway inhibitor Pifithrin-α (PFT-α) also reversed the biological effects of silencing GDI2 on CRC cells. The p-p21 and p-p53 protein expression levels were significantly greater in the sh-GDI2 group than in the sh-NC group. However, the p-p21 and p-p53 protein expression levels were reduced after silencing GDI2 while overexpressing RAB5A. ConclusionSilencing GDI2 activates the p53 signaling pathway by regulating RAB5A expression levels, which in turn induces cell cycle arrest and ultimately affects the proliferative activity, migration, and invasive ability of CRC cells.

Survival and predictors of mortality among colorectal cancer patients on follow-up in Hawassa University Comprehensive Specialized Hospital, Sidama region, Southern Ethiopia, 2022. A 5-year retrospective cohort study.

The incidence and mortality of colorectal cancer were still rising rapidly in many low-income and middle-income countries, which was linked to ongoing societal and economic status. Colorectal cancer is the leading cancer in Ethiopia with relatively lower survival. However, colorectal cancer patients' survival time and predictors have not been well studied in Southern Ethiopia. This study aimed to assess five-year survival and predictors of mortality among colorectal cancer patients at Hawassa Comprehensive Specialized Hospital, Ethiopia. Facility-based retrospective cohort study was conducted among 323 patients who visited Hawassa Comprehensive Specialized Hospital from May 1st, 2017 to April 30th, 2022. The Kaplan-Meier survival curve with the Log-rank test was used to estimate the survival time. Bivariable and multivariable Cox proportional hazards regression models were used to determine the net effect of each independent variable on time to death after diagnosis. Over the 5-year observation period, the overall mortality rate was 38.5%, with an incidence density of 31 fatalities per 100 person-years observation. Survival at 1, 2, 3, 4, and 5 years was 78%, 53, 32.4%, 23.3%, and 18.7% respectively. The multivariable analysis showed that metastatic disease (AHR = 4.2, CI: 1.5-11.5), baseline carcinoembryonic antigen level ≥5ng/ml (AHR: 2.4, CI: 1.2-5.8), living in rural areas (AHR = 2.2, CI:1.03-4.8) and mucinous carcinoma (AHR = 0.33, CI: 0.13-0.87) were independent predictors of colorectal cancer mortality. Overall survival of colorectal cancer patients in the study was low compared to similar studies in developing and developed worlds. A significantly low survival rate was observed for patients with advanced stage, elevated carcinoembryonic antigen levels, and rural residents indicating the key role of early detection and timely initiation of treatment to improve survival and quality of life of patients with colorectal cancer.

Exploring the diagnostic and prognostic significance of circulating tumor cells in stage II-IV colorectal cancer using a nano-based detection method.

Colorectal cancer (CRC) is a leading cause of cancer mortality globally, underscoring the urgency for a noninvasive and effective biomarker to enhance patient prognosis. Circulating tumor cells (CTCs), a potential marker for real-time tumor monitoring, are limited in clinical utility due to the low sensitivity of existing detection methods. Previously, we introduced a novel Nano-based CTCs detection method that relies on the electrical properties of cell surfaces, thus eliminating thereby obviating the need for specific molecular biomarkers. In this study, we employed this technique to evaluate the diagnostic and prognostic value of CTCs in stage II-IV CRC. A total of 194 participants were included, consisting of 136 CRC patients and 58 healthy individuals. The peripheral blood of the participants was collected, and CTCs enumeration was performed utilizing the Nano-based detection method that we newly developed. The Receiver Operating Characteristic (ROC) curve and multivariate Cox proportional-hazards analysis were employed to assess the effectiveness of CTCs for diagnosing CRC and predicting patient prognosis. The Nano-based method demonstrated an ability to differentiate CRC patients from healthy individuals with a sensitivity of 84.6% and a specificity of 94.8%. Furthermore, baseline CTCs levels were predictive of progression-free survival (PFS) in CRC patients, with lower levels associated with longer PFS compared to higher levels (4.5 months vs. 8.0 months at 15 CTCs/mL, p = 0.016; 4.4 months vs. 8.0 months at 20 CTCs/mL, p = 0.028). We also explored the dynamic changes in the number of CTCs after 1-5 cycles of chemotherapy. Patients with increasing CTCs levels typically experienced disease progression (PD), while those with decreasing levels often achieved a partial response (PR) or maintained stable disease (SD). These findings suggest that the dynamic fluctuations in CTCs counts are closely tied to the clinical course of the disease. Our study indicates the potential of Nano-based CTCs detection in diagnosing and predicting outcomes for patients with stage II-IV CRC.

Synthesis and quality assessment of combined time-series and static medical data using a real-world time-series generative adversarial network

This study addresses challenges related to privacy issues in utilizing medical data, particularly the protection of personal information. To overcome this obstacle, the research focuses on data synthesis using real-world time-series generative adversarial networks (RTSGAN). A total of 53,005 data were synthesized using the dataset of 15,799 patients with colorectal cancer. The results of the quantitative evaluation of the synthetic data’s quality are as follows: the Hellinger distance ranged from 0 to 0.25; the train on synthetic, test on real (TSTR) and train on real, test on synthetic (TRTS) results showed an average area under the curve of 0.99 and 0.98; a propensity mean squared error was 0.223. The synthetic and real data were similar in the qualitative methods including t-SNE and histogram analyses. The application of synthetic data in predicting five-year survival in colorectal cancer patients demonstrates comparable performance to models based on real data. This study employs distance to closest records and membership inference test to assess potential privacy exposure, revealing minimal risk. This study demonstrated that it is feasible to synthesize medical data, including time-series data, using the RTSGAN, and the synthetic data can be evaluated to accurately reflect the characteristics of real data through quantitative and qualitative methods as well as by utilizing real-world artificial intelligence models.