Recurrence In Colorectal Cancer Patients Research Articles

A study of the clinical significance of mSEPT9 in monitoring recurrence and prognosis in patients with surgically treated colorectal cancer.

To explore the medical significance of methylated septin9 (mSEPT9) in monitoring recurrence and prognostic assessment in individuals with surgically treated colorectal cancer (CRC). To investigate the role of Septin9 in colorectal cancer, we utilized the TIMER2.0 database to analyze its differential expression between tumor tissues and adjacent normal tissues. Colorectal cancer RNA-seq data from the TCGA database was downloaded and curated. The clinical relevance of mSEPT9 in colorectal cancer was explored by examining the correlation between Septin9 methylation levels and clinical characteristics using UALCAN and MethSurv software. Peripheral blood samples were obtained from 130 CRC subjects who underwent surgery for the detection of mSEPT9 and carcinoembryonic antigen (CEA) expression, along with collection of clinicopathological data such as age, gender, tumor site, TNM stage, and tumor differentiation. Patients were followed up for at least 3 years post-surgery until the death or final follow-up dates (31/12/2022). Additionally, peripheral blood samples were collected from 30 colorectal cancer surgery patients for mSEPT9 detection before and 7 days after surgery. Through bioinformatic database analysis, we identified higher expression levels of SEPT9 mRNA in most tumor tissues compared to normal tissues. Similarly, both paired and unpaired CRC tissues exhibited elevated expression of Septin9 when compared to normal tissues. Following GO and KEGG analysis of Septin9 target genes, we discovered their significant associations with ncRNA metabolic processes, ribonucleoprotein complex biogenesis, spliceosomes, and viral carcinogenesis. Furthermore, the overexpression of mSeptin9 was observed in CRC tissues, and it demonstrated a correlation with colon cancer staging and histologic classification. In our clinical sample study, The positive rate of mSEPT9 in CRC patients 7 days after surgery was 43.44% lower than that of preoperative. The differences in TNM stage, tumor differentiation degree, and preoperative CEA expression level between the preoperative mSEPT9 positive and negative groups of CRC were statistically significant (P < 0.05). Recurrence free survival (RFS) and overall survival (OS) were shorter in the preoperative mSEPT9-positive group, meaning preoperative mSEPT9 status was a risk factor for CRC recurrence and prognosis (P < 0.05). The sensitivity, specificity, and AUC value of preoperative mSEPT9 and CEA levels for predicting postoperative recurrence in CRC patients were 88% vs. 72%, 56.19% vs. 55.24%, and 0.721 vs. 0.636 respectively, well the AUC value of the combined prediction of postoperative recurrence was 0.758. The detection of mSEPT9 combined with CEA in preoperative plasma helps predict recurrence in colorectal cancer patients.

Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery.

This study aimed to investigate the efficacy of thymosin α1 combined with XELOX in improving immune function and reducing serum tumor markers in patients with colorectal cancer (CRC) after radical surgery. A total of 180 patients who underwent radical surgery for CRC were divided into two groups: an observation group (n = 94) receiving thymosin α1 in combination with XELOX and a control group (n = 86) receiving XELOX alone. Immune function, inflammatory factor levels, serum tumor markers, and quality of life were assessed before and after treatment. Adverse reactions and recurrence rates were compared between the two groups in 1 and 3 years. Following therapy, there was a notable increase in the levels of CD3+, CD4+, and CD4+/CD8+ in all cohorts, particularly in the observation cohort, when compared to pre-therapy levels. Conversely, CD8+ levels decreased across all cohorts, especially in the observation cohort. Additionally, there was an increase in the levels of IL-2 and IFN-γ in the observation cohort, compared to both pre-therapy and control cohort levels, while IL-6 levels decreased. The presence of CEA, CA242, and CA724 reduced significantly across all cohorts following post-therapy, particularly in the observation cohort. Post-therapy, there was a significant increase in the scoring for role, cognitive, social, emotional, and somatic functions in all cohorts, with the most significant improvement observed in the observation cohort. There were no significant differences in the incidence of side effects across cohorts, while neutropenia events were significantly lower in the observation cohort (32.98%) compared to the control cohort (48.84%). The 12-month recurrence rate showed no statistical significance across cohorts, while the observation cohort had a significantly lower three-year recurrence rate (24.47%) compared to the control cohort (59.30%). Thymosin α1 combined with XELOX is effective in improving immune function, reducing serum tumor markers, and minimizing recurrence in CRC patients after radical surgery. This combination therapy may be a promising new direction for the treatment of CRC.

Predicting mortality and recurrence in colorectal cancer: Comparative assessment of predictive models

IntroductionColorectal cancer (CRC), also known as colorectal cancer, is a significant disease marked by high fatality rates, ranking as the third leading cause of global mortality. The main objective of this study was to assess the accuracy of predictive models in predicting both mortality events and the probability of disease recurrence. MethodA retrospective analysis was conducted on a cohort of 284 individuals diagnosed with colorectal cancer between 2001 and 2017. Demographic and clinical data, including gender, disease stage, age at diagnosis, recurrence status, and treatment details, were meticulously recorded. We rigorously evaluated various predictive models, including Decision Trees, Random Forests, Random Survival Forests (RSF), Gradient Boosting, mboost, Deep Learning Neural Network (DLNN), and Cox regression. Performance metrics, such as sensitivity, positive predictive value (PPV), specificity, area under the receiver operating characteristic curve (ROC area), and overall accuracy, were calculated for each model to predict mortality and disease recurrence. The analysis was performed using R version 4.1.3 software and the Python programming language. ResultsFor mortality prediction, the mboost model demonstrated the highest sensitivity at 96.9% (95% CI: 0.83–0.99) and an ROC area of 0.88. It also exhibited high specificity at 80% (95% CI: 0.59–0.93), a positive predictive value of 86.1% (95% CI: 0.70–0.95), and an overall accuracy of 89% (95% CI: 0.78–0.96). Random Forests showed perfect sensitivity of 100% (95% CI: 0.85–1) but had low specificity at 0% (95% CI: 0–0.52) and poor overall accuracy (50%). On the other hand, DLNN had the lowest performance metrics for mortality prediction, with a sensitivity of 24% (95% CI: 0.222–0.268), specificity of 75% (95% CI: 0.73–0.77), and a lower positive predictive value of 42% (95% CI: 0.38–0.45). The Gradient Boosting model showed the best performance in predicting recurrence, achieving perfect sensitivity of 100% (95% CI: 0.87–1) and high specificity at 92.9% (95% CI: 0.76–0.99). It also had a high positive predictive value of 93.3% (95% CI: 0.77–0.99). Gradient Boosting, with an ROC area of 96.4%, and mboost, with an ROC area of 75%, demonstrated remarkable performance. DLNN had the lowest performance metrics for recurrence prediction, with sensitivity at 1.75% (95% CI: 0.01–0.02), specificity at 98% (95% CI: 0.97–0.98), and a lower positive predictive value at 52.6% (95% CI: 0.39–0.65). ConclusionIn summary, the mboost model demonstrated outstanding performance in predicting mortality, achieving exceptional results across various evaluation metrics. Random Forests exhibited perfect sensitivity but showed poor specificity and overall accuracy. The DLNN model displayed the lowest performance metrics for mortality prediction. In terms of recurrence prediction, the Gradient Boosting model outperformed other models with perfect sensitivity, high specificity, and positive predictive value. The DLNN model had the lowest performance metrics for recurrence prediction. Overall, the results emphasize the effectiveness of the mboost and Gradient Boosting models in predicting mortality and recurrence in colorectal cancer patients.

Pathological characteristics and long-term prognosis of submucosal infiltrating carcinoma of the colon and rectum below 2 cm confirmed by endoscopic submucosal dissection.

The purpose of this study was to explore the correlation between additional surgery and the clinicopathological characteristics of colorectal cancer, as well as its impact on patient prognosis. A total of 119 patients with early colorectal cancer were selected and divided into an additional surgery group (28 cases) and a non-additional surgery group (91 cases). According to the tumor size, the patients were further divided into a large diameter group (54 cases, d≥1 cm and <2 cm) and a small diameter group (65 cases, d<1 cm). The clinical and pathological characteristics as well as the prognosis of the patients were statistically analyzed. The results showed that infiltration type, depth of infiltration, and tumor size were correlated with additional surgery (P<0.05). Infiltration type and depth of infiltration were closely related to additional surgery. Differentiation degree, infiltration type, and depth of infiltration were correlated with tumor diameter. Infiltration type was closely related to tumor size. Age, depth of infiltration, and tumor size were correlated with patient survival rates. Infiltration type and depth of infiltration were closely related to patient survival rate (P<0.05). They were independent risk factors affecting patient prognosis. The 5-year disease-free survival rates were 73.33% and 72.5%, respectively, with no statistically significant difference. Infiltration type and depth of infiltration were independent risk factors for recurrence in colorectal cancer patients, while depth of infiltration was an independent risk factor for the 5-year survival rate after surgery. They can be used to predict the prognosis of colorectal cancer and guide clinical treatment as a supplement to the traditional staging of colorectal cancer.

Abstract A031: ZEB2 induced EMT drives therapy resistance by activating nucleotide excision repair I gene ERCC1 And ERCC4 n colorectal cancer

Abstract Resistance to adjuvant chemotherapy is a major clinical problem in the treatment of colorectal cancer (CRC). The aim of this study was to elucidate the role of an epithelial to mesenchymal transition (EMT)-inducing protein, ZEB2, in chemoresistance of CRC, and to uncover the underlying mechanism. We performed IHC for ZEB2 and association analyses with clinical outcomes on primary CRC and matched CRC liver metastases in compliance with observational biomarker study guidelines. ZEB2 expression in primary tumors was an independent prognostic marker of reduced overall survival and disease-free survival in patients who received adjuvant FOLFOX chemotherapy. ZEB2 expression was retained in 96% of liver metastases. The ZEB2-dependent EMT transcriptional program activated nucleotide excision repair (NER) pathway largely via upregulation of the ERCC1 gene and other components in NER pathway, leading to enhanced viability of CRC cells upon oxaliplatin treatment. ERCC1-overexpressing CRC cells did not respond to oxaliplatin in vivo, as assessed using a murine orthotopic model in a randomized and blinded preclinical study. Our findings show that ZEB2 is a biomarker of tumor response to chemotherapy and risk of recurrence in CRC patients. We propose that the ZEB2-ERCC1 axis is a key determinant of chemoresistance in CRC. Citation Format: Hajir Al Saihati. ZEB2 induced EMT drives therapy resistance by activating nucleotide excision repair I gene ERCC1 And ERCC4 n colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A031.

Effect of hyperglycemia on the occurrence and prognosis of colorectal cancer.

Hyperglycemic status is associated with the development and prognosis of colorectal cancer (CRC), although the exact mechanisms are not fully understood. Hyperglycemia can promote the development of CRC by influencing cell proliferation and apoptosis, inflammatory responses, oxidative stress, immunomodulation, angiogenesis, and other pathways. In terms of prognosis, hyperglycemia may affect the survival and recurrence of CRC patients as well as chemotherapy resistance, but the results of related studies are not consistent. Hypoglycemic treatment may have a positive impact on the prognosis of CRC patients, but its specific effects need further research. Therefore, this article systematically explores the relationship between hyperglycemia and CRC, analyzes the impact of hyperglycemia on the occurrence and prognosis of CRC, and discusses the role of managing hyperglycemia in CRC.

Long-Term Usage of Proton Pump Inhibitors Associated with Prognosis in Patients with Colorectal Cancer.

The dose-response effect of proton pump inhibitors on colorectal cancer prognosis is still under exploration. This population-based study in Taiwan was designed to examine the effect of proton pump inhibitors on overall death, colorectal cancer-specific death, and recurrence in colorectal cancer patients with different cumulative proton pump inhibitor dose levels. This cohort study was based on the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database from 2005 to 2020. After frequency matching with a 1:1 ratio, a total of 20,889 users with proton pump inhibitors and 20,889 without proton pump inhibitors were analyzed. The cumulative defined daily dose level of proton pump inhibitor was stratified to explore the dose-response relationship. A proton pump inhibitor exposure cumulative defined daily dose > 60 after colorectal cancer diagnosis had higher risk of all-cause death than non-proton pump inhibitor users with adjusted hazard ratios of 1.10 (95% CIs: 1.04-1.18). For recurrence, a proton pump inhibitor exposure cumulative defined daily dose > 60 had reduced recurrence risk with an adjusted hazard ratio of 0.84 (95% CIs: 0.76-0.93). This study demonstrated that the long-term use of proton pump inhibitors in patients with colorectal cancer was associated with an increased risk of death that related to the proton pump inhibitor exposure cumulative defined daily dose > 60 and had different dose-response effect in various dose level.

Development and validation of a novel radiomics nomogram for prediction of early recurrence in colorectal cancer

BackgroundEarly recurrence (ER) is a significant concern following curative resection of advanced colorectal cancer (CRC) and is linked to poor long-term survival. Reliable prediction of ER is challenging, necessitating the development of a novel radiomics-based nomogram for CRC patients. MethodsWe enrolled 405 patients, with 298 in the training set and 107 in the external test set. Radiomic features were extracted from preoperative venous-phase computed tomography (CT) images. A radiomics signature was created using univariate logistic regression analyses and the least absolute shrinkage and selection operator algorithm. Clinical factors were integrated into the analyses to develop a comprehensive predictive tool in a multivariate logistic regression model, resulting in a radiomics nomogram. Subsequently, the calibration, discrimination, and clinical usefulness of the nomogram were evaluated. ResultsThe radiomics signature, consisting of four selected CT features, was significantly associated with ER in both the training and test datasets (P < 0.05). Independent predictors of ER included TNM stage, carcinoembryonic antigen level and differentiation grade were identified. The radiomics nomogram, incorporating all these predictors, exhibited good predictive ability in both the training set with an area under the curve (AUC) of 0.82 (95 % confidence interval (CI), 0.74–0.90) and the test set with an AUC of 0.85 (95 % CI, 0.72–0.99), surpassing the performance of any single candidate factor alone. Furthermore, additional analysis demonstrated that the nomogram was clinically useful. ConclusionsWe have developed a radiomics-based nomogram that effectively predicts early recurrence in CRC patients, enhancing the potential for timely intervention and improved outcomes.

Impact of previous diverticulitis on 5-year survival and recurrence rates in patients with colorectal cancer

Background Diverticulitis and colorectal cancer (CRC) share epidemiological characteristics, but their relationship remains unknown. It is unclear if prognosis following CRC differ for patients with previous diverticulitis compared to those with sporadic cases and patients with inflammatory bowel disease or hereditary syndromes. Aim The aim was to determine 5-year survival and recurrence after colorectal cancer in patients with previous diverticulitis, inflammatory bowel disease and hereditary colorectal cancer compared to sporadic cases. Methods Patients <75 years of age diagnosed with colorectal cancer at Skåne University Hospital Malmö, Sweden, between January 1st 2012 and December 31st 2017 were identified through the Swedish colorectal cancer registry. Data was retrieved from the Swedish colorectal cancer registry and chart review. Five-year survival and recurrence in colorectal cancer patients with previous diverticulitis were compared to sporadic cases, inflammatory bowel disease associated and hereditary colorectal cancer. Results The study cohort comprised 1052 patients, 28 (2.7%) with previous diverticulitis, 26 (2.5%) IBD, 4 (1.3%) hereditary syndromes and 984 (93.5%) sporadic cases. Patients with a history of acute complicated diverticulitis had a significantly lower 5-year survival rate (61.1%) and higher recurrence rate (38.9%) compared to sporadic cases (87.5% and 18.8% respectively). Conclusion Patients with acute complicated diverticulitis had worse 5-year prognosis compared to sporadic cases. The results emphasize the importance of early detection of colorectal cancer in patients with acute complicated diverticulitis.

Postoperative circulating tumor DNA testing based on tumor naïve strategy after liver metastasis surgery in colorectal cancer patients.

There is still a lack of highly sensitive methods for monitoring recurrence of colorectal cancer patients after liver metastasis surgery. The aim of this study was to evaluate the prognostic value of tumor-naive ctDNA detection after resection of colorectal liver metastases (CRLM). Patients with resectable CRLM were prospectively enrolled. Based on the tumor-naive strategy, NGS panels containing 15 colorectal cancer hotspot mutated genes were used to detect ctDNA 3-6 weeks after surgery. A total of 67 patients were included in the study, and the positive rate of postoperative ctDNA was 77.6% (52/67). Patients with positive ctDNA had a significantly higher risk of recurrence after surgery (HR 3.596, 95% CI 1.479 to 8.744, P = 0.005), and a higher proportion relapsed within 3 months after surgery (46.7% vs 3.8%). The C-index of postoperative ctDNA in predicting recurrence was higher than that of CRS and postoperative CEA. The nomogram combining CRS and postoperative ctDNA can improve the accuracy of recurrence prediction. Tumor-naive ctDNA detection can detect molecular residual lesions in patients with colorectal cancer after liver metastasis, and its prognostic value is superior to conventional clinical factors.

Transcriptomes of the tumor-adjacent normal tissues are more informative than tumors in predicting recurrence in colorectal cancer patients

BackgroundPrevious investigations of transcriptomic signatures of cancer patient survival and post-therapy relapse have focused on tumor tissue. In contrast, here we show that in colorectal cancer (CRC) transcriptomes derived from normal tissues adjacent to tumors (NATs) are better predictors of relapse.ResultsUsing the transcriptomes of paired tumor and NAT specimens from 80 Korean CRC patients retrospectively determined to be in recurrence or nonrecurrence states, we found that, when comparing recurrent with nonrecurrent samples, NATs exhibit a greater number of differentially expressed genes (DEGs) than tumors. Training two prognostic elastic net-based machine learning models—NAT-based and tumor-based in our Samsung Medical Center (SMC) cohort, we found that NAT-based model performed better in predicting the survival when the model was applied to the tumor-derived transcriptomes of an independent cohort of 450 COAD patients in TCGA. Furthermore, compositions of tumor-infiltrating immune cells in NATs were found to have better prognostic capability than in tumors. We also confirmed through Cox regression analysis that in both SMC-CRC as well as in TCGA-COAD cohorts, a greater proportion of genes exhibited significant hazard ratio when NAT-derived transcriptome was used compared to when tumor-derived transcriptome was used.ConclusionsTaken together, our results strongly suggest that NAT-derived transcriptomes and immune cell composition of CRC are better predictors of patient survival and tumor recurrence than the primary tumor.

Auricularia polytricha: A promising medicinal mushroom for combination therapy of colorectal cancer and understanding its potential mechanism of action

The Global Burden of Cancer (GLOBOCAN) revealed that there were 1,931,590 new cases and 935,173 deaths due to colorectal cancer in 2020. Treatment for colorectal cancer tends to be invasive and costly. Therefore, further research is needed on non-invasive complementary therapies that are safe and can be used to reduce the probability of recurrence in colorectal cancer patients at an affordable cost. The systematic literature review synthesized resources and presented them in a narrative review. Four databases, including PubMed, Research Gate, ProQuest, and Science Direct, were used to conduct the systematic reviews by following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria. In this review, 36 articles were analyzed descriptively to help describe and summarize the data constructively. The results showed that complementary colorectal cancer therapy with Auricularia polytricha which contains active compounds, such as flavonoids, phenols, and beta-glucans, can increase the expression of miRNA-9, miRNA-217, miRNA-210, miRNA200c, and miRNA-132 which can improve the prognosis of colorectal cancer.

Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy

The mammalian target of rapamycin (mTOR) is often activated in several cancers. We focused on two mTOR regulatory mechanisms: oxaliplatin-induced mTOR signaling and L-type amino acid transporter 1 (LAT1)-induced mTOR activation. High LAT1 expression in several cancers is associated with mTOR activation and resistance to chemotherapy. However, the significance of LAT1 has not yet been elucidated in colorectal cancer (CRC) patients treated with post-operative adjuvant chemotherapy. Immunohistochemistry was conducted to examine the significance of membrane LAT1 expression in 98 CRC patients who received adjuvant chemotherapy, including oxaliplatin. In vitro analysis was performed using CRC cell lines to determine the effects of LAT1 suppression on proliferation, oxaliplatin sensitivity, and mTOR signaling. LAT1 expression was associated with cancer aggressiveness and poor prognosis in 98 CRC patients treated with adjuvant chemotherapy. We found that positive LAT1 expression correlated with shorter survival in 43 patients treated with the capecitabine-plus-oxaliplatin (CAPOX) regimen. LAT1 suppression in CRC cells inhibited the proliferation potency and oxaliplatin-induced activation of mTOR signaling, and improved oxaliplatin sensitivity. LAT1 evaluation before adjuvant treatment may therefore be a sensitive marker for oxaliplatin-based regimens. Moreover, LAT1 may be a promising target for patients with refractory CRC.

A new natural killer cell-specific gene signature predicting recurrence in colorectal cancer patients.

The protective role of Natural Killer (NK) cell tumour immunosurveillance has long been recognised in colorectal cancer (CRC). However, as most patients show limited intra-tumoral NK cell infiltration, improving our ability to identify those with high NK cell activity might aid in dissecting the molecular features which underlie NK cell sensitivity. Here, a novel CRC-specific NK cell gene signature that infers NK cell load in primary tissue samples was derived and validated in multiple patient CRC cohorts. In contrast with other NK cell gene signatures that have several overlapping genes across different immune cell types, our NK cell signature has been extensively refined to be specific for CRC-infiltrating NK cells. The specificity of the signature is substantiated in tumour-infiltrating NK cells from primary CRC tumours at the single cell level, and the signature includes genes representative of NK cells of different maturation states, activation status and anatomical origin. Our signature also accurately discriminates murine NK cells, demonstrating the applicability of this geneset when mining datasets generated from preclinical studies. Differential gene expression analysis revealed tumour-intrinsic features associated with NK cell inclusion versus exclusion in CRC patients, with those tumours with predicted high NK activity showing strong evidence of enhanced chemotactic and cytotoxic transcriptional programs. Furthermore, survival modelling indicated that NK signature expression is associated with improved survival outcomes in CRC patients. Thus, scoring CRC samples with this refined NK cell signature might aid in identifying patients with high NK cell activity who could be prime candidates for NK cell directed immunotherapies.

Transcriptomic Profiling Reveals an Enhancer RNA Signature for Recurrence Prediction in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most fatal malignancies worldwide, and this is in part due to high rates of tumor recurrence in these patients. Currently, TNM staging remains the gold standard for predicting prognosis and recurrence in CRC patients; however, this approach is inadequate for identifying high-risk patients with the highest likelihood of disease recurrence. Recent evidence has revealed that enhancer RNAs (eRNAs) represent a higher level of cellular regulation, and their expression is frequently dysregulated in several cancers, including CRC. However, the clinical significance of eRNAs as recurrence predictor biomarkers in CRC remains unexplored, which is the primary aim of this study. We performed a systematic analysis of eRNA expression profiles in colon cancer (CC) and rectal cancer (RC) patients from the TCGA dataset. By using rigorous biomarker discovery approaches by splitting the entire dataset into a training and testing cohort, we identified a 22-eRNA panel in CC and a 19-eRNA panel in RC for predicting tumor recurrence. The Kaplan-Meier analysis showed that biomarker panels robustly stratified low and high-risk CC (p = 7.29 × 10-5) and RC (p = 6.81 × 10-3) patients with recurrence. Multivariate and LASSO Cox regression models indicated that both biomarker panels were independent predictors of recurrence and significantly superior to TNM staging in CC (HR = 11.89, p = 9.54 × 10-4) and RC (HR = 3.91, p = 3.52 × 10-2). Notably, the ROC curves demonstrated that both panels exhibited excellent recurrence prediction accuracy in CC (AUC = 0.833; 95% CI: 0.74-0.93) and RC (AUC = 0.834; 95% CI: 0.72-0.92) patients. Subsequently, a combination signature that included the eRNA panels and TNM staging achieved an even greater predictive accuracy in patients with CC (AUC = 0.85). Herein, we report a novel eRNA signature for predicting recurrence in patients with CRC. Further experimental validation in independent clinical cohorts, these biomarkers can potentially improve current risk stratification approaches for guiding precision oncology treatments in patients suffering from this lethal malignancy.

Identification of an EMT-related Gene Signature Predicting Recurrence in Stage II/III Colorectal Cancer

To identify a prognostic significant gene signature for predicting colorectal cancer (CRC) recurrence. Traditional prognostic risk assessment in stage II/III CRC patients remains controversial. Epithelial-mesenchymal transition is thought to be closely related to the malignant progression of tumors. Thus, it is promising to establish a prognostic model based on epithelial-mesenchymal transition-related gene (ERG) signature. We retrospectively analyzed transcriptome profiles and clinical information of 1780 stage II/III CRC patients from 15 public datasets. Coefficient variant analysis was used to select reference genes for normalizing gene expression levels. Univariate, LASSO, and multivariate Cox regression analyses were combined to develop the ERG signature predicting disease-free survival (DFS). The patients were divided into high-risk and low-risk based on the ERG signature recurrence risk score. The survival analysis was performed in different CRC cohorts. The proposed ERG signature contained 7 cancer-related ERGs and 3 reference genes. The ERG signature recurrence risk score was prognostically relevant in all cohorts ( P <0.05) and proved as an independent prognostic factor in the training cohort. In the pooled cohort, high-risk CRC patients exhibited worse DFS ( P <0.0001) and overall survival ( P =0.0058) than low-risk patients. The predictive performance of the ERG signature was superior to Oncotype DX colon cancer. An integrated decision tree and nomogram were developed to improve prognosis evaluation. The identified ERG signature is a promising and powerful biomarker predicting recurrence in CRC patients. Moreover, the presented ERG signature might help to stratify patients according to their tumor biology and contribute to personalized treatment.

MicroRNA Expression Profiling Predicts Nodal Status and Disease Recurrence in Patients Treated with Curative Intent for Colorectal Cancer.

Simple SummaryDetermining the degree of nodal involvement provides key prognostic information in several malignancies, including colorectal cancer (CRC). Furthermore, predicting long-term outcomes in such cancers often proves challenging to the multidisciplinary team. Therefore, the purpose of this translational research study was to evaluate the role of mi(cro)RNAs as biomarkers used to predict nodal status and recurrence in patients being treated for CRC. This analysis involved the quantification of miRNA targets in 74 patients with CRC using real-time reverse transcriptase polymerase chain reaction. Aberrant expression of miR-21 and miR-135b correlated with increased metastatic disease in local lymph nodes following resection. Interestingly, increased expression of miR-195 displayed strong capabilities of predicting the time to disease recurrence. These results add to the growing evidence illustrating the value of using miRNA expression profiling to inform patient outcomes in cancer. These findings may be further validated in further studies as we attempt to personalise the management paradigm for prospective patients diagnosed with CRC.Background: Approximately one-third of colorectal cancer (CRC) patients will suffer recurrence. MiRNAs are small non-coding RNAs that play important roles in gene expression. We aimed to correlate miRNA expression with aggressive clinicopathological characteristics and survival outcomes in CRC. Methods: Tumour samples were extracted from 74 CRC patients. MiRNAs were quantified using real-time reverse transcriptase polymerase chain reaction. Descriptive statistics and Cox regression analyses were performed to correlate miRNA targets with clinicopathological and outcome data. Results: Aberrant miR-21 and miR-135b expression correlate with increased nodal stage (p = 0.039, p = 0.022). Using univariable Cox regression analyses, reduced miR-135b (β-coefficient −1.126, hazard ratio 0.324, standard error (SE) 0.4698, p = 0.017) and increased miR-195 (β-coefficient 1.442, hazard ratio 4.229, SE 0.446, p = 0.001) predicted time to disease recurrence. Survival regression trees analysis illustrated a relative cut-off of ≤0.488 for miR-195 and a relative cut-off of >−0.218 for miR-135b; both were associated with improved disease recurrence (p < 0.001, p = 0.015). Using multivariable analysis with all targets as predictors, miR-195 (β-coefficient 3.187, SE 1.419, p = 0.025) was the sole significant independent predictor of recurrence. Conclusion: MiR-195 has strong value in predicting time to recurrence in CRC patients. Additionally, miR-21 and miR-135b predict the degree nodal burden. Future studies may include these findings to personalize therapeutic and surgical decision making.

Immune Cell Proportions and TNM Stage Improve the Prediction of Recurrence in Colorectal Cancer Patients

Immune Cell Proportions and TNM Stage Improve the Prediction of Recurrence in Colorectal Cancer Patients

Prognostic value of FDG PET-CT in suspected recurrence of colorectal carcinoma: survival outcomes of a 10-year follow-up : FDG PET in recurrent colorectal CA.

We aimed to evaluate the predictive value of FDG PET-CT scan and CEA measurements in recurrent colorectal cancer (CRC) patients. The records of 211 CRC patients who had FDG PET-CT scans between April 2009 and June 2011 due to suspicion of recurrence were extracted from the data of our previous report of 235 patients after 24 patients were excluded from the study due to lack of follow-up data or death unrelated to CRC. FDG PET-CT findings, simultaneous CEA levels, and survival data were evaluated retrospectively to determine the prognostic factors that affected the overall survival (OS) of the patients. The mean age of 211 patients was 60.2 ± 12.8years. The median follow-up time was 39months (CI 95%: 4-123months). The CRC-related death rate was 71.6% and the median OS time was measured 39months (CI 95%: 27-50months) for 211 patients. The median OS time for the patients with positive findings for recurrence in PET scans was 28months (CI 95%: 22-33months) which was significantly shorter (p < 0.001) than that of PET-negative patients (median OS was not reached; mean OS: 105months; CI 95%: 95-116months). CEA positivity also had a significant negative effect on survival (p < 0.001). Median OS times in patients with elevated and normal levels of CEA were 24months (CI 95%: 17-30months) and 85months (CI 95%: 62-107months), respectively. When the effect of CEA positivity was evaluated in patients with negative PET scans for recurrence, no statistically significant difference was determined (p = 0.209), but PET positivity had a significant negative effect on OS in patients with normal levels of CEA (p < 0.001). On the other hand, PET negativity had a significant positive effect on OS in patients with elevated CEA levels (p = 0.002). The extend of recurrent disease had also a significant effect on OS. The patients with distant metastasis had less favorable OS than those patients with only local recurrence (p < 0.001). The presence of liver metastasis also diminished the OS, but this effect was not statistically significant (p = 0.177). FDG PET-CT scan which is a reliable imaging method to detect recurrence in CRC patients, regardless of CEA levels, can also provide valuable prognostic information, even superior to that of CEA measurement.

Risk factors for recurrence in colorectal cancer: a retrospective analysis in a regional Australian hospital.

Colorectal cancer is the third most commonly diagnosed malignancy in Australia. Up to a third of patients who have undergone surgery with curative intent for colorectal cancer will have a recurrence of disease leading to significant morbidity and mortality. Regional Australians have disproportionately worse outcomes. To identify factors associated with recurrence in colorectal cancer patients treated at a regional Australian hospital. This study is a retrospective cohort analysis. Consecutive patients who have undergone curative resection at a regional public and private hospital by three surgeons from a single surgical practice for either rectal cancer or colon cancer were included. Prognostic indicators of recurrence were examined via both univariate and multivariate time-to-event analyses. Three hundred nine patients were included with 43 recurrences. Thirty presented with distant metastases, seven presented with locoregional recurrence and six presented with locoregional as well as distant recurrence. In univariable analysis, higher rates of recurrence were associated with tumour type, higher AJCC summary stage, higher preoperative levels of CA19-9, perineural invasion, lymphovascular invasion, <12 nodes examined, positive lymph nodes and emergency surgery status. On multivariable analysis recurrence remained associated with tumours with a mucinous and/or signet cell component, positive nodes and <12 lymph nodes examined. A combination of patient and treatment factors are relevant in determining the risk of recurrence for stage I-III colorectal cancer. This study emphasises the importance of histology in determining risk, particularly the number of nodes examined. CEA 19-9 may also be a useful pre-operative predictor of recurrence.