Overall Survival Of Colon Cancer Patients Research Articles

A nomogram for individually predicting the overall survival in colonic adenocarcinoma patients presenting with perineural invasion: a population study based on SEER database.

Colonic adenocarcinoma, representing the predominant histological subtype of neoplasms in the colon, is commonly denoted as colon cancer. This study endeavors to develop and validate a nomogram model designed for predicting overall survival (OS) in patients with colon cancer, specifically those presenting with perineural invasion (PNI). The Surveillance, Epidemiology, and End Results (SEER) database supplied pertinent data spanning from 2010 to 2015, which facilitated the randomization of patients into distinct training and validation cohorts at a 7:3 ratio. Both univariate and multivariate analyses were employed to construct a prognostic nomogram based on the training cohort. Subsequently, the nomogram's accuracy and efficacy were rigorously evaluated through the application of a concordance index (C-index), calibration plots, decision curve analysis (DCA), and receiver operating characteristic (ROC) curves. In the training cohorts, multivariable analysis identified age, grade, T-stage, N-stage, M-stage, chemotherapy, tumor size, carcinoembryonic antigen (CEA), marital status, and insurance as independent risk factors for OS, all with P-values less than 0.05. Subsequently, a new nomogram was constructed. The C-index of this nomogram was 0.765 (95% CI: 0.755-0.775), outperforming the American Joint Committee on Cancer (AJCC) TNM staging system's C-index of 0.686 (95% CI: 0.674-0.698). Calibration plots for 3- and 5-year OS demonstrated good consistency, while DCA for 3- and 5-year OS revealed excellent clinical utility in the training cohorts. Comparable outcomes were observed in the validation cohorts. Furthermore, we developed a risk stratification system, which facilitated better differentiation among three risk groups (low, intermediate, and high) in terms of OS for all patients. In this study, we have devised a robust nomogram and risk stratification system to accurately predict OS in colon cancer patients exhibiting PNI. This innovative tool offers valuable guidance for informed clinical decision-making, thereby enhancing patient care and management in oncology practice.

Deciphering the Clinical Significance and Kinase Functions of GSK3α in Colon Cancer by Proteomics and Phosphoproteomics

GSK3α and GSK3β are two GSK3 isoforms with 84% overall identity and 98% identity in their catalytic domains. GSK3β plays important roles in the pathogenesis of cancer, while GSK3α has long been considered a functionally redundant protein of GSK3β. Few studies have specifically investigated the functions of GSK3α. In this study, unexpectedly, we found that the expression of GSK3α, but not GSK3β, was significantly correlated with the overall survival (OS) of colon cancer patients in 4 independent cohorts. To decipher the roles of GSK3α in colon cancer, we profiled the phosphorylation substrates of GSK3α and uncovered 156 phosphosites from 130 proteins specifically regulated by GSK3α. A number of these GSK3α-mediated phosphosites have never been reported before or have been incorrectly identified as substrates of GSK3β. Among them, the levels of HSF1S303p, CANXS583p, MCM2S41p, POGZS425p, SRRM2T983p and PRPF4BS431p were significantly correlated with the OS of colon cancer patients. Further pull-down assays identified 23 proteins, such as THRAP3, BCLAF1 and STAU1, showing strong binding affinity to GSK3α. The interaction between THRAP3 and GSK3α was verified by biochemical experiments. Notably, among the 18 phosphosites of THRAP3, phosphorylation at S248, S253 and S682 is specifically mediated by GSK3α. Mutation of S248 to D (S248D), which mimics the effect of phosphorylation, obviously increased cancer cell migration and the binding affinity to proteins related to DNA damage repair. Collectively, this work not only discloses the specific function of GSK3α as a kinase but also suggests GSK3α as a promising therapeutic target for colon cancer.

Prognostic Value of Body Mass Index in Stage II/III Colon Cancer: Posthoc Analysis From the TOSCA Trial

BackgroundHigh body mass index (BMI) plays a key role in the development of colon cancer (CC). Our post-hoc analysis from the TOSCA trial analyzed the association between BMI and survival outcomes in terms of relapse-free survival (RFS) and overall survival (OS) in stage II/III CC patients. Patients and methodsPatients enrolled in the TOSCA trial between 2007-2013 with BMI data entered the study. The prognostic impact of BMI on survival outcomes was investigated through uni- and multivariable Cox regression analyses. ResultsOverall, 1455 patients with stage II/III CC patients were included. The median follow-up was of 61.5 months; 16.1% of patients relapsed, 11.2% died and 19.5% patients relapsed or died. No impact of BMI on RFS was detected at univariate or multivariable analyses. By univariate analysis for OS, a significantly impact of a BMI > 30 kg/m2 was reported (HR [>30 vs <25] 1.57, 95% CI 1.00-2.47, p = 0.049; HR [>30 vs <30] 1.55, 95% CI 1.01-2.37, p = 0.045). Multivariable analyses did not confirm this data. In the subgroup of stage III patients, a negative survival impact of BMI was found in univariate and multivariable models both for RFS and for OS. ConclusionsIn our study, obesity with BMI > 30 kg/m2 was an independent prognostic factor for RFS and OS in CC patients treated with adjuvant chemotherapy, regardless of its duration (3 or 6 months). However, the prognostic impact of adiposity and body composition measurement should be considered to better classify patients with high visceral fat and refine their risk assessment.

ULBP2 is a biomarker related to prognosis and immunity in colon cancer.

The study aimed to determine whether ULBP2 was associated with prognosis and immune infiltration in colon cancer (CC) and provided important molecular basis inorderto early non-invasive diagnosis and immunotherapy of CC. Using The Cancer Genome Atlas database (TCGA) and ImmPort database, we extracted messenger RNA (mRNA) data of CC and immune-related genes, then we used "limma" package, "survival" package, and Venn overlap analysis to obtain the differentially expressed mRNA (DEmRNA) associated with prognosis and immunity of CC patients. "pROC" package was used to analyze receiver operating characteristics (ROC) of target gene. We used chi-square test and two-class logistics model to identify clinicopathological parameters that correlated with target gene expression. In order to determine the effects of target gene expression and clinicopathological parameters on survival, univariate and multivariate cox regression analyses were performed. We analyzed the related functions and signaling pathways of target gene by enrichment analysis. Finally, the correlation between target gene and tumor immune infiltrating was explored by ssGSEA and spearman correlation analysis. Results showed that ULBP2 was a target gene associated with immunity and prognosis in CC patients. CC patients with higher ULBP2 expression had poor outcomes. In terms of ROC, ULBP2 had an area under the curve (AUC) of 0.984. ULBP2 was associatedwith T stage, N stage, and pathologic stage of CC patients, and served as an independent predictor of overall survival in CC patients. Functional enrichment analysis revealed ULBP2 was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of ULBP2 was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and spearman correlation analysis. To conclude, our study suggested that ULBP2 was associated with tumor immunity, and might be a biomarker associated with the diagnosis and prognosis of CC patients, and a potential target of CC immunotherapy.

A microRNA panel that regulates proinflammatory cytokines as diagnostic and prognosis biomarkers in colon cancer

Colon cancer (CC) is the third most common neoplasm and the fourth cause of cancer-related death worldwide in both sexes. It has been established that inflammation plays a critical role in tumorigenesis and progression of CC. Immune, stromal and tumor cells supply the tumor microenvironment with pro-inflammatory cytokines such as interleukin 1β, TNFα, IL-6 and IL-11, to hyperactivate signaling pathways linked to cancerous processes. Recent findings suggest a putative role of microRNAs (miRNAs) in the progression and management of the inflammatory response in intestinal diseases. Moreover, miRNAs are able to regulate expression of molecular mediators that are linking inflammation and cancer. In this work a miRNA panel differentially expressed between healthy, inflammatory bowel disease (IBD) and CC tissue was established. Identified miRNAs regulate signaling pathways related to inflammation and cancer progression. An inflammation associated-miRNA panel composed of 11-miRNAs was found to be overexpressed in CC but not in inflamed or normal tissues (miR-21-5p, miR-304-5p, miR-577, miR-335-5p, miR-21-3p, miR-27b-5p, miR-335-3p, miR-215-5p, miR-30b-5p, miR-192-5p, miR-3065-5p). The association of top hit miRNAs, miR-3065-5p and miR-30b-5p expression with overall survival of CC patients was demonstrated using Kaplan-Meier tests. Finally, differential miRNA expression was validated using an inflammation-associated CC model induced by Azoxymethane/Dextran Sodium Sulfate (AOM/DSS) to compare miRNA expression in normal and inflamed tissue versus CC tissues. Based on these findings we propose the identified inflammatory miRNA panel as a potent diagnostic tool for CC determination.

TPMT mRNA Expression: A Novel Prognostic Biomarker for Patients with Colon Cancer by Bioinformatics Analysis

BackgroundTo explore the clinicopathological significance and prognostic value of thiopurine methyltransferase (TPMT) in patients with colon cancer by bioinformatics analysis.Materials and MethodsThe clinicopathological information and TPMT expression data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Wilcoxon signed-rank test was used to evaluate the relationship between TPMT mRNA expression levels and clinicopathological characteristics in patients with colon cancer. Then, the prognostic value of TPMT mRNA expression for disease-free survival (DFS) and overall survival (OS) in patients with colon cancer was assessed by Kaplan–Meier and Cox regression analyses. Additionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore potential functions of TPMT in patients with colon cancer.ResultsTPMT mRNA was significantly downregulated in colon cancer compared with normal tissues (P < 0.05). Wilcoxon analysis revealed that lower TPMT mRNA expression was remarkably associated with lymph node metastasis (P = 0.008), distant metastasis (P = 0.012) and advanced pathological stage (P = 0.010). Besides, the high TPMT mRNA level was also correlated with a favorable DFS and OS in colon cancer patients (both P < 0.05). Moreover, GO enrichment analysis indicated that the co-expressed genes of TPMT function as extracellular matrix (ECM) structural constituent, insulin-like growth factor binding, cell adhesion molecule binding and growth factor binding. KEGG enrichment analysis suggested that the co-expressed genes of TPMT were particularly enriched in amino sugar and nucleotide sugar metabolism, ECM-receptor interaction and focal adhesion.ConclusionTPMT mRNA level might be a novel prognostic biomarker for patients with colon cancer.

Interaction Between Macrophage Extracellular Traps and Colon Cancer Cells Promotes Colon Cancer Invasion and Correlates With Unfavorable Prognosis.

BackgroundMacrophage extracellular traps (METs) and tumor-infiltrating macrophages contribute to the progression of several diseases. But the role of METs and tumor-infiltrating macrophages in colon cancer (CC) has not been illuminated. In this study, we aimed to clarify the prognostic value of METs for CC patients and to explore the interaction between CC cells and METs in vitro and in vivo.MethodsA training cohort consisting of 116 patients and a validation cohort of 94 patients were enrolled in this study. Immunofluorescence (IF) staining was conducted to determine METs formation in CC patients. Cox regression was used to perform prognostic analysis and screen out the best prognostic model. A nomogram was established to predict 5-year overall survival (OS). The correlation between METs with clinicopathological features and inflammatory markers was analyzed. The formation of METs in vitro was detected by SYTOX® green and IF staining, and the effect of METs on CC cells was detected by transwell assays. PAD2-IN-1, a selective inhibitor of peptidylarginine deiminase 2 (PAD2), was introduced to destroy the crosstalk between CC cells and METs in vitro and in vivo.ResultsMETs levels were higher in CC tissues and were an independent prognostic factor for CC patients. The prognostic model consisting of age, tumors local invasion, lymph node metastasis and METs were confirmed to be consistent and accurate for predicting the 5-year OS of CC patients. Besides, METs were correlated with distant metastasis and inflammation. Through in vitro experiments, we confirmed that there was a positive feedback loop between CC cells and METs, in that METs promoted the invasion of CC cells and CC cells enhanced the production of METs, in turn. This interaction could be blocked by PAD2-IN-1 inhibitors. More importantly, animal experiments revealed that PAD2-IN-1 inhibited METs formation and CC liver metastasis in vivo.ConclusionsMETs were the potential biomarker of CC patient prognosis. PAD2-IN-1 inhibited the crosstalk between CC cells and METs in vitro and in vivo, which should be emphasized in CC therapy.

Identification of an Immune-Related Nine-lncRNA Signature Predictive of Overall Survival in Colon Cancer.

Growing evidence suggests that immune-related genes (IRGs) and long non-coding RNAs (lncRNAs) can serve as prognostic markers of overall survival (OS) in patients with colon cancer. This study aimed to identify an immune-related lncRNA signature for the prospective assessment of prognosis in these patients. Gene expression and clinical data of colon cancer patients were downloaded from The Cancer Genome Atlas (TCGA). Immune-related lncRNAs were identified by a correlation analysis between IRGs and lncRNAs. In total, 447 samples were divided into a training cohort (224 samples) and a testing cohort (223 samples). Univariate, lasso and multivariate Cox regression analyses identified an immune-related nine-lncRNA signature closely related to OS in colon cancer patients in the training dataset. A risk score formula involving nine immune-related lncRNAs was developed to evaluate the prognostic value of the lncRNA signature in the training dataset. Colon cancer patients with a high risk score had poorer OS than those with a low risk score. A multivariate Cox regression analysis confirmed that the immune-related nine-lncRNA signature could be an independent prognostic factor in colon cancer patients. The results were further confirmed in the testing cohort and the entire TCGA cohort. Furthermore, a gene set enrichment analysis revealed several pathways with significant enrichment in the high- and low-risk groups that may be helpful in formulating clinical strategies and understanding the underlying mechanisms. Finally, a quantitative real-time polymerase chain reaction assay found that the nine lncRNAs were significantly differentially expressed in colon cancer cell lines. The results of this study indicate that this signature has important clinical implications for improving predictive outcomes and guiding individualized treatment in colon cancer patients. These lncRNAs could be potential biomarkers affecting the prognosis of colon cancer.

Analysis of risk factors for colon cancer progression.

Purpose: This study aimed to find risk factors for colon cancer progression with bioinformatics methods, and validated by clinical patients.Methods: Differentially expressed genes (DEGs) between colon cancer tissues and normal colon tissues were extracted from The Cancer Genome Atlas (TCGA) database using R software, amounted to 8,051. DEGs between pathologic stage I+II and stage III+IV amounted to 373, and were compared with DEGs of cancer/normal analyzed above to get the intersection of both. Ninety-six intersected DEGs were identified and defined as progressive DEGs of colon cancer. Then these 96 progressive DEGs were studied by Gene ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis using the DAVID database and visualizing by R software. A protein–protein interaction (PPI) network and functional modules were established using the STRING database. Further, an overall survival (OS) curve was drawn via the GEPIA website based on the CGA database and six progressive DEGs were found to be involved with OS of colon cancer patients. The Linkedomics website was used for detailed analysis of specific subsets of TNM.Results: Pregnancy specific glycoprotein (PSG), vitamin digestion, and absorption were confirmed to promote the progression of colon cancer. Furthermore, NTF4 was found to be associated with both OS and each subset of TNM; therefore, defined as a key risk factor for colon cancer progression. Further analysis of NTF4 expression using clinical data showed it acted as a key risk factor and diagnosis marker for colon cancer progression.Conclusion: NTF4 is a risk factor contributing to colon cancer progression and associated with overall survival.

Does the Different Locations of Colon Cancer Affect the Oncologic Outcome? A Propensity-Score Matched Analysis.

PurposeWe evaluate the prognostic value of primary tumor location for oncologic outcomes in patients with colon cancer (CC).MethodsCC patients treated with curative surgery between 2009 and 2012 were classified into 2 groups: right-sided colon cancer (RCC) and left-sided colon cancer (LCC). Recurrence-free survival (RFS) and overall survival (OS) were examined based on tumor stage. Propensity scores were created using eight variables (age, sex, T stage, N stage, histologic grade, presence of lymphovascular invasion/perineural invasion, and microsatellite instability status).ResultsOverall, 2,329 patients were identified. The 5-year RFSs for RCC and LCC patients were 89.7% and 88.4% (P = 0.328), respectively, and their 5-year OSs were 90.9% and 93.4% (P = 0.062). Multivariate survival analyses were carried out by using the Cox regression proportional hazard model. In the unadjusted analysis, a marginal increase in overall mortality was seen in RCC patients (hazard ratio [HR], 1.297; 95% confidence interval [CI], 0.987–1.704, P = 0.062); however, after multivariable adjustment, similar OSs were observed in those patients (HR, 1.219; 95% CI, 0.91–1.633; P = 0.183). After propensity-score matching with a total of 1,560 patients, no significant difference was identified (P = 0.183). A slightly worse OS was seen for stage III RCC patients (HR, 1.561; 95% CI, 0.967–2.522; P = 0.068) than for stage III LCC patients. The 5-year OSs for patients with stage III RCC and stage III LCC were 85.5% and 90.5%, respectively (P = 0.133).ConclusionAlthough the results are inconclusive, tumor location tended to be associated with OS in CC patients with lymph node metastasis, but it was not related to oncologic outcome.

PIK3CD induces cell growth and invasion by activating AKT/GSK-3β/β-catenin signaling in colorectal cancer.

The catalytic subunit p110δ of phosphoinositide 3‐kinase (PI3K) encoded by PIK3CD has been implicated in some human solid tumors. However, its roles in colorectal cancer (CRC) remain largely unknown. Here we found that PIK3CD was overexpressed in colon cancer tissues and CRC cell lines and was an independent predictor for overall survival (OS) of patients with colon cancer. The ectopic overexpression of PIK3CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo. In contrast, inhibition of PIK3CD by specific small‐interfering RNA or idelalisib dramatically suppressed CRC cell growth, migration and invasion in vitro and tumor growth in vivo. Moreover, PIK3CD overexpression increased AKT activity, nuclear translocation of β‐catenin and T‐cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity and decreased glycogen synthase kinase 3β (GSK‐3β) activity, whereas PIK3CD inhibition exhibited the opposite effects. Furthermore, PIK3CD‐mediated cell growth, migration and invasion were reversed by blockade of AKT signaling or depletion of β‐catenin. In addition, PIK3CD expression in colon cancer tissues positively correlated with β‐catenin abnormal expression, which was an independent predictor for OS of colon cancer patients. Taken together, our findings demonstrate that PIK3CD is an independent prognostic factor in CRC and that PIK3CD induces CRC cell growth, migration and invasion by activating AKT/GSK‐3β/β‐catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC.

Comprehensive analysis of metastasis-related genes reveals a gene signature predicting the survival of colon cancer patients.

ObjectiveThe mechanism underlying colon cancer metastasis remain unclear. This study aimed to elucidate the genes alteration during the metastasis of colon cancer and identify genes that crucial to the metastasis and survival of colon cancer patients.MethodsThe dataset of primary and metastasis tissue of colon cancer, and dataset of high and low metastasis capability of colon cancer cells were selected as training cohort, and the overlapped differentially expressed genes (DEGs) were screened from the training cohort. The functional enrichment analysis for the overlapped DEGs was performed. The prognostic value of overlapped DEGs were analyzed in The Cancer Genome Atlas dataset, and a gene signature was developed using genes that related to the overall survival (OS). The prognostic value of the gene signature was further confirmed in a validation cohort.ResultsA total of 184 overlapped DEGs were screened from the training cohort. Functional enrichment analysis revealed the significant gene functions and pathways of the overlapped DEGs. Four hub genes (3-oxoacid CoA-transferase 1, actinin alpha 4, interleukin 8, integrin subunit alpha 3) were identified using protein–protein network analysis. Six genes (aldehyde dehydrogenase 2, neural precursor cell expressed, developmentally down-regulated 9, filamin A, lamin B receptor, twinfilin actin binding protein 1, serine and arginine rich splicing factor 1) were closely related to the OS of colon cancer patients. A gene signature was developed using these six genes based on their risk score, and the validation cohort indicated that the prognostic value of this gene signature was high in the prediction of colon cancer patients.ConclusionsOur study demonstrates a gene profiles related to the metastasis of colon cancer, and identify a six-gene signature that acts as an independent biomarker on the prognosis of colon cancer.

Independent prognostic genes and mechanism investigation for colon cancer

ProposeWe aimed to explore the potential molecular mechanism and independent prognostic genes for colon cancer (CC).MethodsMicroarray datasets GSE17536 and GSE39582 were downloaded from Gene Expression Omnibus. Meanwhile, the whole CC-related dataset were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNA (DEMs) were identified between cancer tissue samples and para-carcinoma tissue samples in TCGA dataset, followed by the KEGG pathway and GO function analyses. Furthermore, the clinical prognostic analysis including overall survival (OS) and disease-free survival (DFS) were performed in all three datasets.ResultsA total of 633 up- and 321 down-regulated mRNAs were revealed in TCGA dataset. The up-regulated mRNAs were mainly assembled in functions including extracellular matrix and pathways including Wnt signaling. The down-regulated mRNAs were mainly assembled in functions like Digestion and pathways like Drug metabolism. Furthermore, up-regulation of UL16-binding protein 2 (ULBP2) was associated with OS in CC patients. A total of 12 DEMs including Surfactant Associated 2 (SFTA2) were potential DFS prognostic genes in CC patients. Meanwhile, the GRP and Transmembrane Protein 37 (TMEM37) were two outstanding independent DFS prognostic genes in CC.ConclusionsULBP2 might be a potential novel OS prognostic biomarker in CC, while GRP and TMEM37 could be served as the independent DFS prognostic genes in CC. Furthermore, functions including extracellular matrix and digestion, as well as pathways including Wnt signaling and drug metabolism might play important roles in the process of CC.

High Expression of lncRNA AFAP1-AS1 Promotes the Progression of Colon Cancer and Predicts Poor Prognosis.

Long non-coding RNAs (lncRNAs) are dysregulated in various cancers. However, the clinical relevance and functional roles of AFAP1-AS1 in colon cancer (CC) have not been clarified. We analyzed the lncRNA expression patterns in Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA) RNA-seq datasets, and found that the expression level of AFAP1-AS1 was significantly elevated in CC tissues. High levels of AFAP1-AS1 were associated with poor disease-free survival and overall survival in CC patients. In vitro experiments demonstrated that AFAP1-AS1 knockdown significantly inhibited the cell invasive and migration capability in CC cell line HT-29. AFAP1-AS1 knockdown also increased the expression of E-cadherin and ZO-1 while inhibited the expression of Vimentin, MMP9, ZEB1 and β-catenin, suggesting that AFAP1-AS1 is involved in the epithelial-mesenchymal transition (EMT) process of CC. Further studies confirmed that AFAP1-AS1 knockdown also affected the actin-cytokeratin signaling pathway. Thus, AFAP1-AS1 might be a potential novel diagnostic marker and therapeutic target for CC.

CHFR methylation as an epigenetic marker for recurrence of colon cancer

4043 Background: Currently, no definitive epigenetic markers exist to predict recurrence and overall survival (OS) of colorectal cancer patients after surgical resection. Promoter hypermethylation of the ID4 (inhibitor of DNA binding), RECK (reversion-inducing cysteine rich protein with Kazal motifs), and CHFR (checkpoint with forkhead-associated and RING finger domains) genes have been associated with reduced mRNA and protein expression in colorectal cancer. The purpose of this study was to determine the association of methylation of these genes and also MINT1 (methylated in tumor loci) with recurrence-free survival (RFS) and OS in colon cancer patients. Methods: DNA methylation was quantitatively evaluated using pyrosequencing in tissue samples from 64 patients with AJCC stage II and III colon cancer without HNPCC seen at M.D. Anderson during 1999–2007. Survival outcomes were determined by retrospective chart review and evaluated by Kaplan-Meier plot and log-rank test for univariate analysis and Cox's proportional hazard model for multivariate analysis. Mean methylation rate of multiple CpG sites in the promoter region was used. For this analysis, we defined &lt;15%, 15%-30%, and &gt;30% as methylation-negative, -low, and -high, respectively. Results: There were 19 stage II (30%) and 45 stage III (70%) patients. The median age was 62.1 years (range: 31–86). Adjuvant chemotherapy was completed in 49 patients (77%). After a median follow-up of 54.9 months, 12 (19%) patients developed recurrence and 7 (11%) have died. Methylation of MINT1, ID4, and RECK did not correlate with RFS and OS. The CHFR methylation-high (42%) group had low RFS (P=.04) and OS (P=.03) when compared with the CHFR methylation- negative (38%) and -low (20%) group. CHFR methylation-high was associated with N2 disease (P=.04) and right-sided tumors (P=.002). Multivariate analysis indicated T4 disease [P=.004, HR=8.42 (95% CI: 1.98–35.8)] and CHFR methylation-high [P=.04, HR = 3.79 (95% CI: 1.04–13.8)], were poor prognostic factors for recurrence. Conclusions: The presence of high CHFR promoter methylation correlates with advanced lymph node metastasis and shortened RFS and OS. Methylation of the CHFR promoter is a potential epigenetic marker for colon cancer recurrence and overall survival. No significant financial relationships to disclose.