Message Framing and Colorectal Cancer Screening
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Neoplasms
PROVIDER: 2193060 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Colorectal cancer (CRC) is among the best examples depicting the relationship between inflammation and increased cancer risk. The introduction of new therapeutic options targeting the inflammatory mediators has been shown to markedly decrease the overall risk of CRC even though their chemopreventive potential is still under debate [1,2]. Specifically, conflicting reports exist concerning the relationship between Infliximab, a monoclonal antibody that specifically blocks Tumor Necrosis Factor (TNF), and an increased risk of CRC in patients with Inflammatory Bowel Disease (IBD). To address the axis between TNF and CRC development and progression, we depleted the Tnf from our previously established murine model of colitis-associated cancer (CAC), the Winnie-ApcMin/+ line. Surprisingly, a detailed histological characterization, demonstrated that the deletion of Tnf in Winnie-ApcMin/+ mice resulted in an initial reduction of dysplastic lesions incidence in 5-week-old mice, followed by faster disease progression with a unique molecular pattern at 8 weeks. Our results highlight that TNF could exert a dual role in CAC supporting the promotion of neoplastic lesions onset at the early stage of the disease and inducing their reduction during disease progression.
2023-05-01 | E-MTAB-12356 | biostudies-arrayexpress
Project description:Circulating microRNA screening of high-risk individuals enrolled in COSMOS lung cancer screening trial.
| PRJNA307356 | ENA
Project description:The project will use exome sequencing to search for genetic predispositions for familial colorectal cancer (CRC). Except for certain syndromes there is today no good method for identifying individuals with a hereditary high risk for CRC (about 25% of the cases). There is currently no routine screening of the population in Norway for CRC today. Coloscopy, which is the most reliable method, is demanding with respect to resources, it can be painful, and may have complications. This project will attempt to find genetic determinants for identification of individuals with increased risk for familial CRC. Such methods will reduce unnecessary medical examination of unaffected family members, and will make it easier to focus health services on individuals with increased risk. This will represent a significant contribution towards improved health reduced death rate caused by CRC. The project includes research on the ethical aspects, in particular challenges related to how feedback to donors is handled.
| 2148709 | ecrin-mdr-crc
Project description:Despite the fact that colorectal cancer (CRC) is one of the most prevalent and deadly cancers in the world, the development of improved and robust biomarkers to enable screening, surveillance, and therapy monitoring of CRC continues to be evasive. In particular, patients with colon polyps are at higher risk of developing colon cancer; however, noninvasive methods to identify these patients suffer from poor performance. In consideration of the challenges involved in identifying metabolite biomarkers in individuals with high risk for colon cancer, we have investigated NMR-based metabolite profiling in combination with numerous demographic parameters to investigate the ability of serum metabolites to differentiate polyp/CRC patients from healthy subjects. We also investigated the effect of disease risk on different groups of biologically related metabolites. Our study may explain some of the challenges and promise a novel avenue for future metabolite profiling methodologies.
2016-12-17 | ST000285 | MetabolomicsWorkbench
Project description:Background and Aims: RNA biomarkers derived from sloughed enterocytes would provide an ideal, non-invasive method for early detection of colorectal cancer (CRC) and precancerous adenomas. To realize this goal, a highly reliable method to isolate preserved human RNA from stool samples is needed. Here we develop a protocol to identify RNA biomarkers associated with CRC to assess the use of these biomarkers for noninvasive screening of disease. Methods: Stool samples were collected from 454 patients prior to a colonoscopy. A nucleic acid extraction protocol was developed to isolate human RNA from 330 stool samples and transcript abundances were estimated by microarray analysis. This 330-patient cohort was split into a training set of 265 individuals to develop a machine learning model and a testing set of 65 individuals to determine the model’s ability to detect colorectal neoplasms. Results: Analysis of the transcriptome from 265 individuals identified 200 transcript clusters as differentially expressed (p<0.03). These transcripts were used to build a Support Vector Machine (SVM) based model to classify 65 individuals within the testing set. This SVM algorithm attained a 95% sensitivity for precancerous adenomas and a 65% sensitivity for CRC (stage I-IV). The machine learning algorithm attained a specificity of 59% for healthy individuals and an overall accuracy of 72.3%. Conclusions: We developed an RNA-based neoplasm detection model that is sensitive for CRC and precancerous adenomas. The model allows for non-invasive assessment of tumors and could potentially be used to provide clinical guidance for individuals within the screening population for colorectal cancer.
2019-02-25 | GSE99573 | GEO
Project description:There are ~1.4 million cases of colorectal cancer (CRC) annually worldwide. Due to recent implementation of bowel cancer screening (BCS), incidence of diagnosis with stage I (T1/2, N0, M0) CRC has increased nearly four-fold; from approximately 12% pre-screening to approximately 42-45%. While survival rates for patients diagnosed with stage I CRC remains above 95%, and identification of patients at this early stage provides the best opportunity to improve in cancer survival rates, recent data has provided quantitative evidence that metastatic seeding can occur from disseminated cells at the very earliest stage of CRC development. The aim of study was to give an insight into aggressive “born-to-be-bad” biology through generation and transcriptional profiling of a novel case-controlled retrospective T1 CRC discovery cohort. We performed transcriptional and histological profiling to identify molecular pathology features of the high-risk metastatic phenotypes, discriminating between relapse and non-relapse T1 lesions and found that a cohort of aggressive early disseminating stage 1 CRC is associated with high cell intrinsic TGFB signalling and not stromal signalling.
2021-11-30 | GSE162667 | GEO
Project description:By integrating genome-wide copy number alteration, RNA-seq and proteomics data from 589 colorectal cancer (CRC) patients, we revealed that chromosome 8q24.21 amplification is negatively correlated with p53 protein stability. Using siRNA and CRISPR activation screening, we pinpointed a novel long noncoding gene (PiHL, P53 inHibiting LncRNA) from 8q24.21 as a p53 negative regulator. PiHL is drastically upregulated in CRC and is an independent predictor of CRC poor prognosis. Further In vitro and In vivo models demonstrate that PiHL is crucial in maintaining cell proliferation and inhibiting cell apoptosis through a p53-depedent manner. Mechanistically, PiHL acts to promote p53 ubiquitination by sequestering RPL11 from MDM2, through enhancing GRWD1 and RPL11 complex formation. We further show that p53 can form a feedback loop with PiHL by directly binding to PiHL promoter and regulating its expression. Our study successfully illustrates how cancer cells hijack the PiHL-p53 axis to promote CRC progression and suggests PiHL as a potential therapeutic target in human CRCs.
2019-12-31 | GSE124526 | GEO
Project description:Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators that regulate these key cellular programs in CRC, we developed an endogenous reporter system by genome-editing human CRC cell lines with knock-in fluorescent reporters at the SOX9 and KRT20 locus to report aberrant stem cell-like activity and differentiation respectively in pooled CRISPR screening formats. We then constructed a dual reporter system that simultaneously monitors aberrant stem cell-like and differentiation activity in the same CRC cell line, improving our signal to noise discrimination. Using a focused-library CRISPR screen targeting 78 epigenetic regulators with 542 sgRNAs, we identified factors that contribute to stem cell-like activity and differentiation in CRC. Perturbation single cell RNA sequencing (Perturb-seq) of validated hits nominated SMARCB1 of the SWI/SNF BAF complex as a negative regulator of differentiation across an array of neoplastic colon models. SMARCB1 is a dependency in CRC and required for human CRC cell line and patient-derived organoid growth in vivo. These studies highlight the utility of a biologically designed endogenous reporter system to uncover novel therapeutic targets for drug development.
2023-07-05 | GSE236257 | GEO