Dataset Information

Point of Care, Real-Time Urine Metabolomics Test to Diagnose Colorectal Cancers and Polyps in Low-and Middle-Income Countries

ABSTRACT: Study description: the study is a clinical trial aimed at assessing the validity of a point-of-care tool developed for colorectal cancer screening using urine metabolites. Objectives: Primary Objective: In the pilot phase, investigators will field test the POC device in Nigeria on 75 patients who are high-risk for CRC and then validate the urine metabolite signature using a large cohort of 645 patients at high risk for CRC and polyps. This will allow us to determine the sensitivity and specificity of this device and these signatures for CRC and polyps. Endpoints: the endpoint will be the calculation of the validity (sensitivity and specificity) of the tool. Positive and negative predictive values will also be calculated. Study population: Patients > 40 years of age with LGI bleeding for more than one-week OR * Patients who are high risk due to a family history of CRC (first-degree relative) * Must be at most 10 years younger than when relative presented with CRC (For example, a patient with a relative diagnosed at age 40 with CRC will be eligible after age 30) * Patients with a diagnosis of stage I-III CRC who have no evidence of disease Both males and females will be involved in the study I. The study will evaluate the validity and acceptability of the POC biosensor device in Nigeria. Description of sites/facilities enrolling participants: the study will be conducted at Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC) which hosts the head office of African Research Group for Oncology (ARGO). The study will also run concurrently at other ARGO collaborating sites. All the ARGO collaborating sites are tertiary health care facilities with experienced personnel to oversee the study. The pilot study will, however, take place in OAUTHC alone. Study duration: The accrual time for the validation study is 2.5 years. Participant Duration: the study will require initial one-time contact. Those that are positive during the screening with the POC biosensor device will be booked for colonoscopy. Hence, for participants with positive results to complete the study may require 2 weeks on average.

DISEASE(S): Colorectal Neoplasms,Colorectal Cancer Screening

PROVIDER: 4641 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Background an Aim: Epigenetics are thought to play a major role in the carcinogenesis of patients that develop multiple colorectal cancers (CRC) in the non-hereditary setting. Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the underlying epigenetic signature that differentiates multiple from solitary colorectal cancer tumors using a genome-scale DNA methylation profiling. Patients and Methods: We used a population-based cohort (EPICOLON II) of 12 patients with synchronous CRC and 29 age- sex- and tumor location-paired solitary CRC patients. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significantly hypermethylated CpG sites results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP) using the Infinium DNA methylation data; KRAS and BRAF mutations; microsatellite instability; and immunohistochemistry for MLH1/MSH2/MSH6/PMS2. Functional annotation clustering of differentially methylated genes between multiple and solitary CRCs was performed. Results: We identified 102 CpG sites that showed significant DNA hypermethylation in multiple versus solitary tumors (difference in M-NM-2 value >0.1 and p<0.05). Methylight assays validated the array results for 4 selected significantly hypermethylated genes (MAP1B, HTRA1, ALOX15, TIMP3) identified in the profiling (p=0.0002). Based on the Infinium data, 8/12 (66.6%) of multiple tumors were classified as CIMP-high, as compared to 5/29 (17%) solitary tumors (p=0.004). CIMP-high tumors displayed significant hypermethylation in 301 CpG sites (difference in M-NM-2 value >0.1; p value <0.05). Interestingly, 76/102 (74.5%) of the hypermethylated CpG sites found in multiple vs. solitary tumors were also seen to be hypermethylated in CIMP-H tumors. Functional analysis of hypermethylated genes found in multiple vs. solitary tumors showed the presence and enrichment of genes involved in different tumorigenic functions. Conclusions: Multiple colorectal cancers are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity in the non-hereditary scenario, and provide novel potential biomarkers for identifying high-risk patients and tailoring surveillance strategies. We used a population-based cohort (EPICOLON II) of 12 patients with synchronous CRC and 29 solitary CRC patients. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay.

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Point of Care, Real-Time Urine Metabolomics Test to Diagnose Colorectal Cancers and Polyps in Low-and Middle-Income Countries

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