Effects of Incomplete ERAS on Clinical Outcomes in Patients With Colorectal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Neoplasms,Enhanced Recovery After Surgery
PROVIDER: 2735223 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Interventions: study group, control group:incomplete ERAS
Primary outcome(s): 5-year Disease free survival and overall survival
Study Design: Cohort study
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Project description:The diagnosis of Kawasaki disease (KD) is often difficult to distinguish from adenovirus (HAdV) and Group A streptococcal disease (GAS). We sought to: 1) to define the KD transcriptional signature that can aid in the diagnosis of complete and incomplete KD in children; 2) to identify specific biomarkers that objectively discriminate between KD and other mimicking conditions, including HAdV and 3) to test the prognostic utility of GEP to determine response to IVIG therapy and development of coronary artery lesions (CAL). Methods: Blood RNA samples were analyzed from 76 pediatric patients with complete KD, 13 with incomplete KD, 19 patients with HAdV, 17 patients with GAS disease, and age- and sex-matched healthy controls (HC). We used class comparisons (MW p< 0.01, Benjamini-Hochberg, and 1.25 fold change filter), class prediction, modular analysis and MDTH analyses to define the specificity of the KD profiles and identify markers of severity. Results: Statistical group comparisons identified 7,899 genes differentially expressed in 39 complete KD patients versus HC (KD biosignature). This signature was validated in another 37 patients with complete KD and in 13 patients with incomplete KD. Modular analysis in children with complete KD demonstrated overexpression of inflammation, neutrophils, myeloid cell, coagulation cascade, and cell cycle genes. The KNN class prediction algorithm identified 25-classifier genes that differentiated children with KD vs HAdV infection in two independent cohorts of patients with 96% (95% CI [80%-99%]) sensitivity and 95% [74%-99%] specificity. MDTH scores in KD patients significantly correlated with the baseline c-reactive protein (R=0.29, p=0.008) and was four fold higher than in children with HAdV (p<0.01). In addition, KD patients that remained febrile 36 hours after treatment with IVIG (non-responders) demonstrated higher baseline, pre-treatment MDTH values compared with responders [12,290 vs. 5,572 respectively; p=0.009]. Conclusion: Transcriptional signatures can be used as a tool to discriminate between KD and HAdV infection, and may also provide prognostic information. 113 samples, no replicates, 9 HAdV, 57 cKD, 12 FUO, 13 GAS, 3 GAS/SF, 5 inKD, 14 healthy control
2016-04-14 | E-GEOD-68004 | biostudies-arrayexpress
Project description:The TP53-R337H founder mutation exists at high frequency throughout southern Brazil and represents the most common germline TP53 mutation reported to date. It was originally identified in pediatric adrenocortical tumors in families with no reported history of cancer. The R337H mutation has since been found in association with early-onset breast cancers and Li-Fraumeni syndrome. To study this variability in tumor susceptibility we generated a knockin mutant p53 mouse model (R334H). Endogenous murine R334H is naturally expressed at abnormally high levels in multiple tissues and is functionally compromised in a cell type and stress-specific manner. The mutant p53 mice develop tumors with long latency and incomplete penetrance, consistent with many human carriers being at a low, but elevated risk for cancer We used microarrays to compare the global programme of gene expression in thymocytes obtained from WT or TP53R337H/R337H mutant mice that had either received 5 Gy whole body irradiation or no irradiation.
2021-03-01 | GSE166819 | GEO
Project description:The diagnosis of Kawasaki disease (KD) is often difficult to distinguish from adenovirus (HAdV) and Group A streptococcal disease (GAS). We sought to: 1) to define the KD transcriptional signature that can aid in the diagnosis of complete and incomplete KD in children; 2) to identify specific biomarkers that objectively discriminate between KD and other mimicking conditions, including HAdV and 3) to test the prognostic utility of GEP to determine response to IVIG therapy and development of coronary artery lesions (CAL). Methods: Blood RNA samples were analyzed from 76 pediatric patients with complete KD, 13 with incomplete KD, 19 patients with HAdV, 17 patients with GAS disease, and age- and sex-matched healthy controls (HC). We used class comparisons (MW p< 0.01, Benjamini-Hochberg, and 1.25 fold change filter), class prediction, modular analysis and MDTH analyses to define the specificity of the KD profiles and identify markers of severity. Results: Statistical group comparisons identified 7,899 genes differentially expressed in 39 complete KD patients versus HC (KD biosignature). This signature was validated in another 37 patients with complete KD and in 13 patients with incomplete KD. Modular analysis in children with complete KD demonstrated overexpression of inflammation, neutrophils, myeloid cell, coagulation cascade, and cell cycle genes. The KNN class prediction algorithm identified 25-classifier genes that differentiated children with KD vs HAdV infection in two independent cohorts of patients with 96% (95% CI [80%-99%]) sensitivity and 95% [74%-99%] specificity. MDTH scores in KD patients significantly correlated with the baseline c-reactive protein (R=0.29, p=0.008) and was four fold higher than in children with HAdV (p<0.01). In addition, KD patients that remained febrile 36 hours after treatment with IVIG (non-responders) demonstrated higher baseline, pre-treatment MDTH values compared with responders [12,290 vs. 5,572 respectively; p=0.009]. Conclusion: Transcriptional signatures can be used as a tool to discriminate between KD and HAdV infection, and may also provide prognostic information.
2016-04-14 | GSE68004 | GEO
Project description:RATIONALE: Learning about quality of life, symptoms, and health behaviors in colorectal cancer survivors may help to determine the long-term effects of colon and rectal cancer treatments and may help to improve the quality of life for future cancer survivors.
PURPOSE: This clinical trial is looking at patient-reported outcomes in long-term survivors of colon and rectal cancers.
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Project description:MyoD is known to transdifferentiate fibroblasts into muscle-like cells. Despite phenotypic resemblance and expression of myogenic marker genes in transdifferentiated cells, our global gene expression data suggests that ~100 genes, many involved in muscle development and function, remain non-reprogrammed. To understand this incomplete reprogramming, we characterized genome-wide chromatin accessibility and MyoD binding in human primary myoblasts and in MyoD-induced skin fibroblast cells. Our analyses revealed thousands of sites with incomplete chromatin reprogramming.Combined analyses of gene expression and epigenetic profiles revealed that many myogenic genes not upregulated during the transdifferentiation process have undergone MyoD-dependent chromatin remodeling, but to a significantly lower extent than reprogrammed genes. Our findings suggest that incomplete MyoD-induced transdifferentiation is due to chromatin-remodeling deficiencies, and that additional factors are required to transdifferentiate cells into a state more similar to myoblasts.
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Project description:MyoD is known to transdifferentiate fibroblasts into muscle-like cells. Despite phenotypic resemblance and expression of myogenic marker genes in transdifferentiated cells, our global gene expression data suggests that ~100 genes, many involved in muscle development and function, remain non-reprogrammed. To understand this incomplete reprogramming, we characterized genome-wide chromatin accessibility and MyoD binding in human primary myoblasts and in MyoD-induced skin fibroblast cells. Our analyses revealed thousands of sites with incomplete chromatin reprogramming.Combined analyses of gene expression and epigenetic profiles revealed that many myogenic genes not upregulated during the transdifferentiation process have undergone MyoD-dependent chromatin remodeling, but to a significantly lower extent than reprogrammed genes. Our findings suggest that incomplete MyoD-induced transdifferentiation is due to chromatin-remodeling deficiencies, and that additional factors are required to transdifferentiate cells into a state more similar to myoblasts.
2017-01-07 | GSE93258 | GEO
Project description:MyoD is known to transdifferentiate fibroblasts into muscle-like cells. Despite phenotypic resemblance and expression of myogenic marker genes in transdifferentiated cells, our global gene expression data suggests that ~100 genes, many involved in muscle development and function, remain non-reprogrammed. To understand this incomplete reprogramming, we characterized genome-wide chromatin accessibility and MyoD binding in human primary myoblasts and in MyoD-induced skin fibroblast cells. Our analyses revealed thousands of sites with incomplete chromatin reprogramming.Combined analyses of gene expression and epigenetic profiles revealed that many myogenic genes not upregulated during the transdifferentiation process have undergone MyoD-dependent chromatin remodeling, but to a significantly lower extent than reprogrammed genes. Our findings suggest that incomplete MyoD-induced transdifferentiation is due to chromatin-remodeling deficiencies, and that additional factors are required to transdifferentiate cells into a state more similar to myoblasts.
2017-01-07 | GSE93257 | GEO
Project description:Whole-genome gene expression analysis has been successfully utilized to diagnose, prognosticate, and identify potential therapeutic targets for cardiovascular disease. However, the utility of this approach to identify outcome-related genes and dysregulated pathways following first-time myocardial infarction (AMI) remains unknown and may offer a novel strategy to detect affected expressome networks that predict long-term outcome. Whole-genome microarray and targeted cytokine expression profiling on blood samples from normal cardiac function controls and first-time AMI patients within 48-hours post-MI revealed expected differential gene expression profiles enriched for inflammation and immune-response pathways in AMI patients. To determine molecular signatures at the time of AMI that could prognosticate long-term outcomes, transcriptional profiles from sub-groups of AMI patients with (n=5) or without (n=22) any recurrent events over an 18-month follow-up were compared. This analysis identified 559 differentially expressed genes. Bioinformatic analysis of this differential gene set for associated pathways revealed 1) increasing disease severity in AMI patients is associated with a decreased expression of the developmental epithelial-to-mesenchymal transition, and 2) modulation of cholesterol transport genes that include ABCA1, CETP, APOA1, and LDLR is associated with clinical outcome. In conclusion, differentially regulated genes and modulated pathways were identified that predicted recurrent cardiovascular outcomes in first-time AMI patients. This cell-based approach for risk stratification in AMI warrants a larger study to determine the role of metabolic remodeling and regenerative processes required for optimal outcomes. A validated transcriptome assay could represent a novel, non-invasive platform to anticipate modifiable pathways and therapeutic targets to optimize long-term outcome for AMI patients. The overall experimental design includes blood samples from 21 control and 31 myocardial infaction patient groups. Among the 31patients, 5 patients have recurrent events. Microarray were peformed on the blood samples and comparisons of control vs patient and patients with recurrent events vs patients without recurrent events were performed to identify differential genes related to disease or patients groups with recurrent events for the following bioinformatic analysis.
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Project description:Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer, but less than half of patients have a clinical complete response to this treatment. To define the molecular features that are associated with response to neoadjuvant therapy, we generated and collected genomic and transcriptomic data from 712 cancers prior to treatment from our own data and from publicly available data. We found that patients with a complete response have decreased risk of local recurrence and future metastasis. We identified multiple differences in DNA mutations and transcripts between complete and incomplete responders. Complete responder tumors have a higher tumor mutation burden and many more significant co-occurring mutations than the incomplete responder tumors. In addition, mutations in DNA repair genes (across multiple mechanisms of repair) were enriched in complete responders and they also had lower expression of these genes indicating that defective DNA repair is associated with complete response to nCRT. Using logistic regression, we identified three significant predictors of complete response: tumor size, mutations within specific network genes, and the existence of three or more concurrent mutations. In tumors that do not completely respond to nCRT, abnormal cell-cell interaction and increased cancer associated fibroblasts were associated with recurrence. Additionally,gene expression analysis identified a subset of immune hot tumors with worse outcomes and upregulation of immune checkpoint proteins. Overall, our study provides a comprehensive understanding of the molecular features associated with response to nCRT and the molecular differences in non-responder tumors that later reoccur. This knowledge may provide critical insight into the development of precision therapy for rectal cancer.
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