Outcome In Colorectal Cancer Patients Research Articles

Targeting the CDK7-MDK axis to suppresses irinotecan resistance in colorectal cancer

AimsColorectal cancer (CRC) remains a major global health issue, with metastatic cases presenting poor prognosis despite advances in chemotherapy and targeted therapy. Irinotecan, a key drug for advanced CRC treatment, faces challenges owing to the development of resistance. This study aimed to understand the mechanisms underlying irinotecan resistance in colorectal cancer. Main methodsWe created a cell line resistant to irinotecan using HT29 cells. These resistant cells were utilized to investigate the role of the CDK7-MDK axis. We employed bulk RNA sequencing, conducted in vivo experiments with mice, and analyzed patient tissues to examine the effects of the CDK7-MDK axis on the cellular response to irinotecan. Key findingsOur findings revealed that HT29 cells resistant to irinotecan, a crucial colorectal cancer medication, exhibited significant phenotypic and molecular alterations compared to their parental counterparts, including elevated stem cell characteristics and increased levels of cytokines and drug resistance proteins. Notably, CDK7 expression was substantially higher in these resistant cells, and targeting CDK7 effectively decreased their survival and tumor growth, enhancing irinotecan sensitivity. RNA-seq analysis indicated that suppression of CDK7 in irinotecan-resistant HT29 cells significantly reduced Midkine (MDK) expression. Decreased CDK7 and MDK levels, achieved through siRNA and the CDK7 inhibitor THZ1, enhanced the sensitivity of resistant HT29 cells to irinotecan. SignificanceOur study sheds light on how CDK7 and MDK influence irinotecan resistance in colorectal and highlights the potential of MDK-targeted therapies. We hypothesized that irinotecan sensitivity and overall treatment efficacy would improve by inhibiting MDK. This finding encourages a careful yet proactive investigation of MDK as a therapeutic target to enhance outcomes in colorectal cancer patients.

Developing and validating a Modified Cachexia Index to predict the outcomes for colorectal cancer after radical surgery.

It was reported that the cachexia index (CXI: ) was an essential index for predicting the prognosis of tumor patients. However, since for SMI needs to be measured by CT imaging methods and its calculation was inconvenient. Thus, we developed a modified cachexia index (mCXI: ). The purpose of this study was to evaluate the association between mCXI and prognosis in patients with colorectal cancer. An analysis of 215 patients with newly diagnosed colorectal cancer was carried out retrospectively. An optimal cut-off value of mCXI was established by the receiver operating characteristic (ROC) curves for predicting prognosis. Prognostic implications of mCXI were investigated using Kaplan-Meier curves and Cox regression analysis. A comparative assessment of the predictive capacity between mCXI and the CXI was performed using time-dependent receiver operating characteristic analysis. Patients were classified into two groups based on the cut-off value of mCXI: the LOW mCXI group (n = 60) and the HIGH mCXI group (n = 155). The 3-year Overall survival (OS) (76.6% vs 96.7%, p < 0.01) and 3-year Recurrence-free survival (RFS) (68.3% vs 94.1%, p < 0.01) were significantly worse in the LOW mCXI group in contrast to that in the HIGH mCXI group. In Cox multivariate regression analysis, mCXI was an independent prognostic factor for OS (HR = 8.951, 95%CI: 3.105-25.807, <0.01). Moreover, compared with CXI (AUC = 0.723), mCXI (AUC = 0.801) has better predictive efficacy, indicating that mCXI is more suitable for prognostic assessment. The mCXI significantly correlated with survival outcomes for colorectal cancer patients after radical surgery.

Association of Serum Proteases and Acute Phase Factors Levels with Survival Outcomes in Patients with Colorectal Cancer

Colorectal cancer (CRC) represents a substantial burden on global healthcare, contributing to significant morbidity and mortality worldwide. Despite advances in screening methodologies, its incidence remains high, necessitating continued efforts in early detection and treatment. Neoplastic invasion and metastasis are primary determinants of CRC lethality, emphasizing the urgency of understanding underlying mechanisms to develop effective therapeutic strategies. This study aimed to explore the potential of serum biomarkers in predicting survival outcomes in CRC patients, with a focus on cathepsin B (CB), leukocytic elastase (LE), total sialic acid (TSA), lipid-associated sialic acid (LASA), antitrypsin activity (ATA), C-reactive protein (CRP), and cystatin C (CC). We recruited 185 CRC patients and 35 healthy controls, assessing demographic variables, tumor characteristics, and 7 serum biomarker levels, including (1) CB, (2) LE, (3) TSA, (4) LASA, (5) ATA, (6) CRP, and (7) CC. Statistical analyses included ANOVA with Tukey’s post hoc tests and MANOVA for continuous variables. Student’s t-test was used for dependent samples, while non-parametric tests like Mann–Whitney U and Wilcoxon signed-rank tests were applied for variables deviating from the normal distribution. Categorical variables were assessed using chi-square and Kruskal-Wallis tests. Spearman’s rank correlation coefficient was utilized to examine variable correlations. Survival analysis employed the Kaplan–Meier method with a log-rank test for comparing survival times between groups. Significant associations were observed between CB (p = 0.04), LE (p = 0.01), and TSA (p = 0.008) levels and survival outcomes in CRC patients. Dukes’ classification stages also showed a significant correlation with survival (p = 0.001). However, no significant associations were found for LASA, ATA, CRP, and CC. Multivariate analysis of LE, TSA, and ATA demonstrated a notable correlation with survival (p = 0.041), notwithstanding ATA’s lack of significance in univariate analysis (p = 0.13). CB, LE, and TSA emerged as promising diagnostic markers with prognostic value in CRC, potentially aiding in early diagnosis and treatment planning. Further research is needed to validate these findings and explore additional prognostic indicators.

Association of Serum Proteases and Acute Phase Factors Levels with Survival Outcomes in Patients with Colorectal Cancer.

Colorectal cancer (CRC) represents a substantial burden on global healthcare, contributing to significant morbidity and mortality worldwide. Despite advances in screening methodologies, its incidence remains high, necessitating continued efforts in early detection and treatment. Neoplastic invasion and metastasis are primary determinants of CRC lethality, emphasizing the urgency of understanding underlying mechanisms to develop effective therapeutic strategies. This study aimed to explore the potential of serum biomarkers in predicting survival outcomes in CRC patients, with a focus on cathepsin B (CB), leukocytic elastase (LE), total sialic acid (TSA), lipid-associated sialic acid (LASA), antitrypsin activity (ATA), C-reactive protein (CRP), and cystatin C (CC). We recruited 185 CRC patients and 35 healthy controls, assessing demographic variables, tumor characteristics, and 7 serum biomarker levels, including (1) CB, (2) LE, (3) TSA, (4) LASA, (5) ATA, (6) CRP, and (7) CC. Statistical analyses included ANOVA with Tukey's post hoc tests and MANOVA for continuous variables. Student's t-test was used for dependent samples, while non-parametric tests like Mann-Whitney U and Wilcoxon signed-rank tests were applied for variables deviating from the normal distribution. Categorical variables were assessed using chi-square and Kruskal-Wallis tests. Spearman's rank correlation coefficient was utilized to examine variable correlations. Survival analysis employed the Kaplan-Meier method with a log-rank test for comparing survival times between groups. Significant associations were observed between CB (p = 0.04), LE (p = 0.01), and TSA (p = 0.008) levels and survival outcomes in CRC patients. Dukes' classification stages also showed a significant correlation with survival (p = 0.001). However, no significant associations were found for LASA, ATA, CRP, and CC. Multivariate analysis of LE, TSA, and ATA demonstrated a notable correlation with survival (p = 0.041), notwithstanding ATA's lack of significance in univariate analysis (p = 0.13). CB, LE, and TSA emerged as promising diagnostic markers with prognostic value in CRC, potentially aiding in early diagnosis and treatment planning. Further research is needed to validate these findings and explore additional prognostic indicators.

High expression of RUNX1 in colorectal cancer subtype accelerates malignancy by inhibiting HMGCR

Colorectal cancer (CRC) presents a complex landscape, characterized by both inter-tumor and intra-tumor heterogeneity. RUNX1, a gene implicated in modulating tumor cell growth, survival, and differentiation, remains incompletely understood regarding its impact on CRC prognosis. In our investigation, we discerned a positive correlation between elevated RUNX1 expression and aggressive phenotypes across various CRC subtypes. Notably, knockdown of RUNX1 demonstrated efficacy in restraining CRC proliferation both in vitro and in vivo, primarily through inducing apoptosis and impeding cell proliferation. Mechanistically, we unveiled a direct regulatory link between RUNX1 and cholesterol synthesis, mediated by its control over HMGCR expression. Knockdown of RUNX1 in CRC cells triggered HMGCR transcriptional activation, culminating in elevated cholesterol levels that subsequently hindered cancer progression. Clinically, heightened RUNX1 expression emerged as a prognostic marker for adverse outcomes in CRC patients. Our findings underscore the pivotal involvement of RUNX1 in CRC advancement and its potential as a therapeutic target. The unique influence of RUNX1 on cholesterol synthesis and HMGCR transcriptional regulation uncovers a novel pathway contributing to CRC progression.

Fear of progression among colorectal cancer patients: a latent profile analysis.

Fear of progression (FoP) leads to poor clinical outcomes in colorectal cancer patients. The study aimed to clarify the profiles and influencing factors of FoP among colorectal cancer patients. A cross-sectional study was conducted with 409 colorectal cancer patients. Convenience sampling method was used to select colorectal cancer patients hospitalized in a tertiary-level hospital in Nanjing as the survey subjects. General information questionnaire, Fear of Progression Questionnaire-Short Form, Distress Disclosure Index, and Social Support Rating Scale were used to collect the data. Latent profile analysis was used to explore the latent profiles of FoP in colorectal cancer patients. Additionally, the influencing factors of profiles were explored by Univariate Analysis and Binomial Logistic Regression Analysis. Latent profile analysis identified two subgroups of fear of disease progression: the "fear low-risk profile (83%)", and the "severe fear profile (17%)." Patients with low age, low social support utilization, first hospital admission, severe healthcare burden, and preoperative bowel symptoms were prone to severe fear of disease progression. There is some heterogeneity in the level of postoperative fear of disease progression in colorectal cancer patients. Doctors and nurses should focus on patients with severe fear and take targeted preventive and psychological care for patients' fear of disease progression as early as possible according to the distribution characteristics of different categories.

Characteristics and Outcomes of Colorectal Cancer Patients Cared for by the Multidisciplinary Team in the Reggio Emilia Province, Italy.

Colorectal cancer emerged as the third most prevalent malignancy worldwide, affecting nearly 2 million individuals in the year 2020. This study elucidates the pivotal role of a multidisciplinary team (MDT) in influencing the prognosis, as measured by relative survival rates, depending upon the stage and age. Cases recorded in an Italian Cancer Registry between 2017 and 2018 were included. Relative survival was reported at 1 and 3 years after diagnosis comparing MDT vs. no-MDT approaches. During the study period, 605 CRCs were recorded while 361 (59.7%) were taken care of by an MDT. Compared to no-MDT, MDT patients were younger with earlier stages and received more surgery. One year after diagnosis, survival was 78.7% (90% in MDT vs. 62% in no-MDT); stratifying by stage, in the MDT group there was no survival advantage for stage I (97.2% vs. 89.9%) and II (96.8% vs. 89.4%), but an advantage was observed for stage III (86.4% vs. 56.9%) and stage IV (63.7% vs. 27.4%). Similar values were observed at 3 years where a marked advantage was observed for stages III (69.9% vs. 35.1%) and IV (29.2% vs. 5.1%). The univariable analysis confirmed an excess risk in the no-MDT group (HR 2.6; 95% CI 2.0-3.3), also confirmed in the multivariable regression analysis (HR 2.0; 95% CI 1.5-2.5). Despite the increase in the number of MDT patients in 2018 (from 50% to 69%), this does not correspond to an improvement in outcome.

Plasma 25-hydroxyvitamin D deficiency in the peri-operative period is associated with survival outcome in colorectal cancer patients: a meta-analysis

AimSurgery had a significant impact on 25-hydroxyvitamin D (25-(OH)D) levels. Uncertainty still existed regarding the effects of peri-operative 25(OH)D deficiency on colorectal cancer (CRC) patients’ prognosis. The purpose of the present study was to explore the potential association between the peri-operative 25(OH)D deficiency and the survival outcome of CRC.MethodsSeven electronic databases [including PubMed, EMBASE, Web of Science, The Cochrane Library, OvidMEDLINE(R), China National Knowledge Infrastructure (CNKI) and Wangfang data] were searched without language limitations. The primary outcomes were overall survival and all-cause mortality. Secondary outcomes were the incidence of 25(OH)D deficiency and risk variables for low 25(OH)D level in the peri-operative period.Results14 eligible studies were obtained with 9324 patients for meta-analysis. In the peri-operative period, the pooled incidence of blood 25(OH)D deficiency was 59.61% (95% CI: 45.74–73.48). The incidence of blood 25(OH)D deficiency post-operatively (66.60%) was higher than that pre-operatively (52.65%, 95% CI: 32.94–72.36). Male (RR = 1.09, 95% CI: 1.03–1.16), rectum tumor (RR = 1.23, 95% CI: 1.03–1.47), spring and winter sampling (RR = 1.24, 95% CI: 1.02–1.49) were the risk factors for the 25(OH)D deficiency. The association between the low 25(OH)D post-operatively and short-term overall survival (HR = 0.43, 95% CI: 0.24–0.77) was most prominent, while a low 25(OH)D pre-operatively (HR = 0.47, 95% CI: 0.31–0.70) was more significantly associated with long-term all-cause mortality than that after surgery.ConclusionPeri-operative 25(OH)D impacted the CRC patients’ prognosis. Due to possible confounding effects of systemic inflammatory response (SIR), simultaneous measurement of vitamin D and SIR is essential for colorectal survival.

Inflammatory Burden Index as a promising new marker for predicting surgical and oncological outcomes in colorectal cancer

AbstractAimsThe prognosis of colorectal cancer (CRC) has been historically reliant on the Tumor Node Metastasis (TNM) staging system, but there is variability in outcomes among patients at similar stages. Therefore, there is an urgent need for more robust biomarkers. The aim of this study was to assess the clinical feasibility of the recently reported Inflammatory Burden Index (IBI) for predicting short‐ and long‐term outcomes in patients with CRC.MethodsThis was a retrospective observational study of 555 CRC patients undergoing surgery for primary tumor resection. We determined the prognostic value of preoperative IBI for disease‐free and overall survival, and its predictive value for perioperative risk of infectious complications, including surgical site infection.ResultsIncreased preoperative IBI was significantly associated with advanced disease stage and poor oncological outcome in CRC patients. Higher IBI was independently linked to poorer disease‐free and overall survival. Similar outcomes were observed in a subanalysis focused on high‐risk stage II and stage III CRC patients. Elevated preoperative IBI was significantly correlated with an increased risk of surgical site infection and other postoperative infectious complications. Propensity score‐matching analysis validated the impact of IBI on the prognosis in CRC patients.ConclusionWe established preoperative IBI as a valuable predictive biomarker for perioperative risks and oncological outcomes in CRC patients. Preoperative IBI is useful for designing effective perioperative management and postoperative oncological follow‐up.

Chemokines as Prognostic Factor in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.

Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes. Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications. A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2.70, 95%-CI: 1.57 to 4.66, p = 0.0003) as well as disease-free survival (HR = 2.68, 95%-CI: 1.41 to 5.08, p = 0.0026). All other chemokines showed either heterogeneous results or few studies were available. The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets.

Clinical Outcome of Colorectal Cancer Patients with Concomitant Hypertension: A Systematic Review and Meta-Analysis.

Arterial hypertension is regarded as a possible biomarker of treatment efficacy in colorectal cancer. Also, extended anti-angiogenic use in the metastatic treatment of the colorectal neoplasm may result in elevated blood pressure. We carried out a systematic review and meta-analysis to assess the clinical outcome of colorectal cancer patients with concomitant hypertension (HTN). We conducted a systematic search on Embase, Web of Science, Scopus, PubMed (Medline), the Cochrane Library, and CINAHL from inception until October 2023 for articles that addressed the relationship between HTN and progressive free survival (PFS), overall survival (OS), and overall response rate (ORR) for the first and second line of systemic therapy in patients with metastatic colorectal cancer. Eligibility criteria were met by 16 articles out of 802 screened studies. Pooled analysis showed that HTN was associated with significantly improved PFS (HR: 0.507, 95% CI: 0.460-0.558, p ≤ 0.001) and OS (HR: 0.677, 95% CI: 0.592-0.774, p ≤ 0.001) in patients with metastatic colorectal cancer. In addition, the pooled RR of HTN for the ORR (RR: 1.28, 95% CI: 1.108-1.495, p = 0.001) suggests that HTN could be a predictive factor of ORR in patients with metastatic colorectal cancer. Elevated blood pressure is associated with better clinical outcomes in patients with metastatic colorectal cancer.

The m6A reader HNRNPC predicts adverse prognosis and promotes the progression of colorectal cancer.

As a critical m6A RNA methylation regulator, HNRNPC has been revealed to serve as potential biomarkers in various human cancers. The specific expression and significance of HNRNPC in colorectal cancer remain unknown. This study aimed to confirm HNRNPC expression level and evaluate its function in colorectal cancer progression. 101 paired tissue samples were collected from colorectal cancer patients. HNRNPC levels in colorectal cancer were detected using PCR. CCK8 and transwell assays were conducted to estimate the effect of HNRNPC on cell growth and metastasis with the regulation of HNRNPC by cell transfection. Upregulated HNRNPC was observed in colorectal cancer compared with normal tissues and cells. The higher HNRNPC levels in tumor tissues were associated with the advanced TNM stage and positive lymph node metastasis. Meanwhile, HNRNPC upregulation could indicate adverse outcomes of colorectal cancer patients. In vitro, the knockdown of HNRNPC significantly suppressed the proliferation, migration, and invasion of colorectal cancer cells. Upregulated HNRNPC served as a biomarker for the prognosis and development of colorectal cancer, which provides a novel therapeutic target for colorectal cancer.

The Impact of Type 2 Diabetes Mellitus on Treatment Outcomes in Patients Operated for Stage III Rectal Adenocarcinoma

Introduction: Colorectal cancer (CRC) ranks as the world&amp;#39;s fourth most prevalent cancer and is the third leading cause of death globally. Stage III CRC indicates localized spread to nearby lymph nodes without metastasis to other body parts. While numerous studies have explored outcomes in CRC patients based on various predictive factors, a comprehensive literature review has identified a gap in research specifically investigating surgical outcomes for stage III rectal adenocarcinoma in individuals with type 2 diabetes mellitus (DM2).Aim: To explore the impact of DM2 on treatment outcomes in patients undergoing surgery for stage III rectal adenocarcinoma.Patients and methods: Our retrospective cohort study involved 95 patients who underwent elective radical anterior rectal resection with established mechanical colorectal anastomosis. Patients were categorized into two groups based on DM2 status.Results: Univariate regression analysis demonstrated that DM2 patients face a significantly higher risk of preoperatively elevated carcinoembryonic antigen levels and postoperative complications such as surgical site infection, urinary issues, and anastomotic leakage. Kaplan-Meier analysis indicated a shorter time to complication onset, particularly anastomotic leakage, and a diminished overall survival in DM2 patients.Conclusion: DM2 emerged as a significant prognostic factor influencing the treatment outcomes of patients undergoing surgery for stage III rectal adenocarcinoma.

Trends and disparities in colorectal cancer hospitalizations and outcomes: a 10-year joinpoint trend study

Background Colorectal cancer (CRC) poses a significant burden on healthcare systems globally. Sociodemographic factors intricately influence CRC epidemiology, yet their impact on inpatient care remains underexplored. This study aimed to assess trends in CRC hospitalization and the effect of sociodemographic factors on outcomes of CRC patients. Methods A retrospective longitudinal analysis was conducted using data from the Healthcare Cost and Utilization Project National Inpatient Sample. Trends in CRC admissions were assessed, stratified by sociodemographic variables. Disparities in hospital-associated outcomes were examined. Statistical methods included multivariable regression and joinpoint regression analysis. Results The prevalence of CRC hospitalizations uptrended from 760 per 100,000 hospitalizations in 2010 to 841 per 100,000 hospitalizations in 2019 (P trend < 0.001). The mean age decreased from 67 to 66 years (P < 0.001). Male gender and White race were predominant across the study period. Inpatient mortality decreased from 4.5% in 2010 to 4.16% in 2019 (P trend = 0.033). On sex subgroup analysis, men had a significantly higher mortality rate (P = 0.034). Racially, Blacks had the highest mortality rate (P = 0.550) and only Whites showed a significant decline in mortality over the study period (P = 0.003). Hospitalization length decreased while total hospital charges increased. Conclusion Our study highlights sociodemographic disparities in CRC outcomes, emphasizing the need for targeted interventions to address inequity in screening, diagnosis, and treatment. Continued research is needed to inform effective healthcare practices in mitigating these disparities and improving survival outcomes.

Molecular Landscape and Therapeutic Strategies against Colorectal Cancer.

Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Although the overall incidence of CRC is decreasing, the incidence of young-onset CRC, characterized by a diagnosis of CRC before age 50, is increasing. Outcomes for CRC patients are improving, partly due to comprehensive molecular characterization of tumors and novel therapeutic strategies. Advances in genomic and transcriptomic analyses using blood- and tumor-tissue-based sequencing have facilitated identification of distinct tumor subtypes harboring unique biological characteristics and therapeutic vulnerabilities. These insights have led to the development and incorporation of targeted therapies and immunotherapy in CRC treatment. In this review, we discuss the molecular landscape and key oncogenes/tumor suppressors contributing to CRC tumorigenesis, metastasis, and therapeutic resistance. We also discuss personalized therapeutic strategies for subsets of CRC patients and provide an overview of evolving novel treatments being evaluated in clinical trials.

The effects of a nurse-led discharge planning on the health outcomes of colorectal cancer patients with stomas: A randomized controlled trial

BackgroundNursing care of colorectal cancer patients with stomas presents unique challenges, particularly during the transition from hospital to home. Early discharge programs can assist patients during this critical period. However, the effects of delivering a nurse-led discharge planning program remain under-studied. ObjectiveEvaluate the effects of a nurse-led discharge planning on the quality of discharge education, stoma self-efficacy, readiness for hospital discharge, stoma quality of life, incidence of stoma complications, unplanned readmission rate, and length of stays. DesignAssessor-blind parallel-arm randomized controlled trial with a repeated-measures design. Setting(s)Participants were recruited from inpatients in the colorectal surgery unit of a university-affiliated hospital in Fujian, China. ParticipantsA total of 160 patients with colorectal cancer who received enterostomy surgery and were scheduled to be discharged to their homes. MethodParticipants were randomly allocated to the experimental and control groups. The former received nurse-led discharge planning in addition to the usual discharge education, while the control group received only the usual discharge education. The program included an assessment, health education, stoma care, stoma support, discharge review, discharge medication and checklist integration, discharge referral, and post-hospital follow-up. Baseline data were collected prior to the intervention (T0). Data on the quality of discharge teaching, readiness for hospital discharge, stoma self-efficacy, and stoma quality of life were measured on the day of discharge from the hospital (T1). Patients' stoma self-efficacy and quality of life were repeat-measured 30 (T2) and 90 days post-discharge (T3). Data on stoma complications (T1, T2, T3), length of stays (T1), and unplanned readmission (T2, T3) were collected from medical records. ResultsParticipants in the intervention group showed significant improvement in the quality of discharge teaching, readiness for hospital discharge, stoma self-efficacy, stoma quality of life, complications, and unplanned readmission, compared to the control group (p < 0.001). However, no statistically significant differences were observed in length of stays (p > 0.05). ConclusionsThe program was effective for improving quality of discharge teaching, readiness for hospital discharge, stoma self-efficacy, and stoma quality of life, as well as for reducing complications and unplanned readmission among stoma patients. Integration of discharge planning into the usual process of care is recommended for clinical practice to facilitate a successful transition from hospital to home. RegistrationThis study was registered at the Chinese clinical trial registry (ChiCTR2200058756) on April 16, 2022, and participant recruitment was initiated in May 2022.

Association of preoperative and recurrent serum carcinoembryonic antigen and outcome of colorectal cancer patients with metastatic relapse

BackgroundSeldom have the associations of preoperative CEA (p-CEA) and recurrent CEA (r-CEA) levels as well as changes in p-CEA and r-CEA with survival in patients with stage I–III colorectal cancer (CRC) who have experienced metastatic relapse, been thoroughly examined. Methods241 consecutive patients with stage I–III CRC who experienced metastatic relapse at Fudan University Shanghai Cancer Center (FUSCC) between January 2008 and January 2016 were investigated. The influence of p-CEA, r-CEA and CEA alteration on the overall survival (OS) and relapse-to-death survival (RDS) was evaluated. The restricted cubic spline regression model was employed to explore the optimal cut-off value of CEA. ResultsAll 241 patients were categorized into four groups built on their CEA alteration patterns as follows: A, patients presenting elevated p-CEA levels but normal r-CEA levels (P–N); B, patients displaying normal levels of both p-CEA and r-CEA (N–N); C, patients exhibiting elevated levels of both p-CEA and r-CEA (P–P); D, patients with normal p-CEA levels but elevated r-CEA levels (N–P). The correlation between p-CEA and OS (P = 0.3266) and RDS (P = 0.2263) was insignificant. However, r-CEA exhibited a significant association with both OS (P = 0.0005) and RDS (P = 0.0002). Group A demonstrated the longest OS and RDS, whereas group D exhibited the poorest OS and RDS outcomes. For both OS and RDS, the CEA alteration groups served as an independent prognostic indicator. The optimal cut-off threshold for CEA was determined to be 5.1 ng/ml via the restricted cubic spline regression model. Conclusionr-CEA has a stronger correlation with OS and RDS in individuals with stage I–III CRC who have experienced metastatic relapse.The change between p-CEA and r-CEA could further indicate post-relapse survival, thereby facilitating the assessment of mortality risk stratification in stage I-III CRC patients experiencing metastatic relapse.

Abstract 6211: Clinical and prognostic assessment of the lncRNA ZFAS1-related gene signature in colorectal cancer

Abstract Colorectal cancer (CRC) is one of the leading causes of cancer death with a rapidly rising incidence rate in younger adults. It is projected to be the leading cause of death in adults under 50 years old by 2030. Although progress over the last couple of decades has improved the clinical management of patients affected by CRC, there is a lack of accurate biomarkers to stratify CRC patients. Among several other biomolecules, lncRNAs (long non-coding RNAs) are non-coding transcripts under 200 nucleotides that can regulate gene expression. Furthermore, lncRNAs are important players in oncogenesis and cancer progression and have the potential to be used as reliable biomarkers. Through this study, we explored the clinical relevance of lncRNAs in colorectal cancer. To analyze the distribution of lncRNAs, we utilized de-identified FFPE (formalin-fixed paraffin-embedded) blocks from Augusta University (n = 88). FFPE blocks were sectioned to extract tissue segments and were subsequently stained using H&amp;E (hematoxylin and eosin dyes) to identify the tumor and adjacent normal regions. The quantification of the gene expression was performed using a medium-throughput NanoString platform. Further analyses were performed using clinicopathological features of the institutional cohort and an independent Cancer Genome Atlas (TCGA) dataset. TCGA contains genomic data along with clinical and molecular characterization of over 11,000 samples of various lineages. In the institutional cohort, ZFAS1 showed higher gene expression in the low survival group for stage II and III colorectal cancer patients, while no significant difference was observed in stage I and IV patients. ZFAS1 expression did not significantly correlate with other clinicopathological parameters, including race, alcohol consumption, tobacco consumption, age, grade, and family history of cancer. In an orthogonal TCGA analysis, higher ZFAS1 expression was associated with genomic perturbations, including significantly altered tumor mutational burden (TMB), aneuploidy, fractional genome alteration, and microsatellite instability. Further, a 21-gene signature was developed for prognostication using gene co-expression network analysis. The gene signature was significantly associated with overall and disease-free survival in the TCGA-CRC cohort. Immune deconvolution analysis of the RNA sequencing data revealed that higher expression of the 21-gene signature was associated with increased infiltration of regulatory T cells while being inversely correlated with the overall level of T cells. In conclusion, our study identified the clinicopathological role of ZFAS1 lncRNA and its interaction genes with prognostic significance in colorectal cancer. Further investigation into the therapeutic relevance of the ZFAS1-related gene signature may prove invaluable in improving the clinical outcomes of colorectal cancer patients. Citation Format: Pankaj Kumar Ahluwalia, Tiffanie Leeman, Ashis Mondal, Ashutosh Vashisht, Harmanpreet Singh, Nivin Omar, Kimya Jones, Ravindra Kolhe. Clinical and prognostic assessment of the lncRNA ZFAS1-related gene signature in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6211.

Abstract 866: Identification of survival-associated epithelial cell markers linked to TROP2 through single-cell and bulk sequencing analysis

Abstract Introduction: Colorectal Cancer (CRC) is known for its aggressiveness and drug resistance. This has increased the interest in antibody-drug conjugates (ADCs) as a possible therapy. In this study, we aim to investigate the effects of the ADC target TROP2, on the level of epithelial cells and its correlation with survival outcomes in CRC patients. Methods: Single-cell RNA (scRNA) data was downloaded from Gene Expression Omnibus (GEO) for CRC patients and evaluated for TROP2 expression. Patients were grouped into low and high-TROP2 based on median TROP2 expression, and pseudo-bulk analysis was used to find the differentially expressed genes (DEGs). The DEGs were used to find the survival association in the TCGA-CRC cohort. A risk score was built using principal component analysis (PCA) on the TROP2-DEGs and cutoff point was chosen based on survival. Kaplan-Meier curve was used to compare overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) risk groups. Gene Set Variation Analysis (GSVA) was used to identify the enriched pathways between low- and high-TROP2 in GSE using pseudo-bulk by pooling epithelial cells of individual patients. Results: Of the 10424 cells of 15 different types for 9 CRC patients retrieved from GSE146771, TROP2 was significantly expressed by epithelial cells (n = 766) with mean expression of 1.64 (SD: 1.96, P-value: 0.003) using pseudo-bulk analysis. Three significant DEGs were obtained which are: KIF13B, UCHL3, and PLAC8. These were evaluated for survival association in resectable stages (I-III) CRC patients (n = 419) using PCA to group the patients into low-risk (n = 88) and high-risk (n = 331), using -1.4 as the cutoff point. High risk group showed a better survival with a 1-year survival probability of 94% compared to 90% in the low group and a 5-year survival probability of 74% vs. 46% in the low group. The Kaplan-Meier curve showed that OS, PFS &amp; DFS were significantly better in the low-risk group (p-value = 0.004, 0, 04, and 0.024 respectively). TROP2 and PLAC8 were significantly associated with worse prognosis, whereas UCHL3 was associated with better prognosis (p-value = &amp;lt;0.001), however, KIF3B did not significantly affect the prognosis. APC gene mutation and TP53 were higher in the low-risk group (p-value = 0.004, 0.007 respectively). KRAS-signaling, IL-18-signaling, MET activation of PTK2-signaling were upregulated in high-TROP2 group, while MYC targets, MTORC1 signaling, DNA repair, reactive-oxygen-species signaling, and TCR-signaling were upregulated in low-TROP2. Conclusion: In this study we developed a TROP2-associated risk score that significantly predicted OS, PFS, and DFS in patients with resectable CRC by combining single-cell and bulk-RNA-seq datasets and showing predominant expression of TROP2 in epithelial cells. These findings support the development of TROP2 targeting therapeutics in this space. Citation Format: Noor Nedal Al-Bzour, Ayah Nedal Al-Bzour, Azhar Saeed, Lujia Chen, Anwaar Saeed. Identification of survival-associated epithelial cell markers linked to TROP2 through single-cell and bulk sequencing analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 866.

Abstract 3421: Associations of circulating levels of tryptophan-kynurenine metabolites and inflammation biomarker neopterin with overall survival among patients with stage I-III colorectal cancer

Abstract Introduction: Dysregulation of the kynurenine pathway of tryptophan metabolism has been linked to the development of inflammation-related chronic diseases, such as colorectal cancer (CRC). Circulating concentrations of certain kynurenine metabolites, the kynurenine/tryptophan ratio (KTR), and the pro-inflammatory marker neopterin increase during inflammation, particularly in response to interferon-gamma. However, comprehensive data on the associations between inflammation markers and kynurenine metabolites and clinical outcomes in CRC patients are lacking. To address this gap in knowledge, we investigated associations of circulating kynurenine metabolites and neopterin with overall survival (OS) in prospectively followed non-metastatic CRC patients. Methods: Pre-surgery blood samples from 2,101 stage I-III CRC patients participating in the international FOCUS consortium were used to measure circulating levels of nine tryptophan-kynurenine pathway metabolites and neopterin using liquid chromatography-tandem mass spectrometry. Multivariable linear regression models and Spearman partial correlation analyses were conducted to quantify associations between kynurenine metabolites and neopterin. Based on the results from correlation analyses, a subset of patients (n=984) was categorized into different groups (‘kynurenine metabolite/neopterin‘: i.e. ‘low/high‘, ‘high/high‘) using the median biomarker concentration as cut-off. Associations of biomarkers with OS were assessed using Cox proportional hazards regression models. All models were adjusted for age at diagnosis, sex, tumor stage, tumor site, circulating creatine levels and cohort. Results: Tryptophan was inversely correlated with neopterin (r=−0.21, β=−0.48, Plinear&amp;lt;0.001). Neopterin was positively correlated with kynurenine (kyn) (r=0.25, β=0.57, Plinear&amp;lt;0.001), the KTR (r=0.42, β=0.87, Plinear&amp;lt;0.001), 3-hydroxykynurenine (r=0.26, β=0.32, Plinear&amp;lt;0.001), anthranilic acid (r=0.29, β=0.36, Plinear&amp;lt;0.001), and quinolinic acid (QA) (r=0.41, β=0.56, Plinear&amp;lt;0.001). After a median follow-up of 3.2 years for OS, 14% (141) patients deceased. While patients with ‘high neopterin’ levels had a 43% increased risk of death (HR, 1.43, 95%CI 0.95-2.16), the ‘high kyn/high neopterin‘ patient group had a 52% increased risk of death (HR, 1.52, 95%CI 1.04-2.22). Similarly, the ‘high QA/high neopterin‘ and ‘high KTR/high neopterin‘ patient groups had a 85% and 89% increased risk of death, respectively (HRQA/Neopt, 1.85, 95%CI 1.24-2.75, HRKTR/Neopt, 1.89, 95%CI 1.27-2.80). Conclusion: Tryptophan-kynurenine pathway activation correlates with inflammation marker neopterin in CRC. Combined associations of kynurenine metabolites and neopterin may be a promising predictor for OS among stage I-III CRC patients. Citation Format: Victoria Damerell, Eline H. van Roekel, Stefanie Brezina, Dieuwertje E. Kok, Tengda Lin, Daniëlle D. Holthuijsen, Jennifer Ose, Caroline Himbert, Simone J. P. Eussen, Arve Ulvik, Fränzel J. van Duijnhoven, Jane C. Figueiredo, Christopher I. Li, Erin M. Siegel, Martin Schneider, David Shibata, Adetunji A. Toriola, Alexis B. Ulrich, Per M. Ueland, Matty P. Weijenberg, Andrea Gsur, Ellen Kampman, Cornelia M. Ulrich, Biljana Gigic. Associations of circulating levels of tryptophan-kynurenine metabolites and inflammation biomarker neopterin with overall survival among patients with stage I-III colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3421.