Catch the cancer; towards a cfDNA-based test for colorectal cancer screening
Ontology highlight
ABSTRACT:
DISEASE(S): Lynch Syndrome, Colorectal Cancer
PROVIDER: 2443182 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:We explored the differential methylation patterns found in cfDNA between no neoplasia (NN; individuals with no colorectal findings, benign pathologies and non-advanced adenomas) and patients with advanced neoplasia (AN; advanced adenomas and colorectal cancer) using pooled samples, for the discovery of non-invasive methylation biomarkers for CRC screening. cfDNA was extracted from serum samples and methylation measurements were assessed with the Infinium MethylationEPIC BeadChip. Data was mainly preprocessed and analyzed with R/Bioconductor packages.
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Project description:We explored the differential methylation patterns found in cfDNA between healthy controls (individuals with no colorectal findings, NCF) and patients with advanced neoplasia (advanced adenomas and colorectal cancer, AA andCRC) using pooled samples, to determine if pooled serum cfDNA samples can be used to search for non-invasive methylation biomarkers, as an affordable and efficient alternative to tissue biopsy. cfDNA was extracted from serum samples and methylation measurements were assessed with the Infinium MethylationEPIC BeadChip. Data was mainly preprocessed and analyzed with R/Bioconductor packages.
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Project description:This study was conducted to explore the serum methylome of precancerous lesions belonging to the serrated pathway of colorectal carcinogenesis in a prospective multicentre cohort. Individuals were grouped into five main categories: (i) serrated adenocarcinoma (SAC), (ii) high-risk serrated polyps (HR-SP) comprising traditional serrated adenomas (TSA), sessile serrated lesions (SSL), and serrated polyps (SP) with dysplasia or ≥ 10 mm; (iii) high-risk hyperplastic polyps (HR-HP), defined as HP ≥ 10 mm; (iv) low-risk serrated lesions (LR-SL) including SP without dysplasia < 10 mm and HP < 10 mm; and (v) healthy individuals with no colorectal findings (NCF). First, epigenome-wide methylation levels were quantified in pooled cfDNA samples to characterize the differential methylation profile between no serrated neoplasia (NSN: NCF and LR-SL) and high-risk serrated lesions (HR-SL: HR-HP and HR-SP); concordance with tissue methylation levels was assessed using external datasets. Then, the pathway-specific cfDNA methylation signature was evaluated together with cfDNA pools from the conventional CRC pathway. cfDNA was extracted from serum samples and methylation measurements were assessed with the Infinium MethylationEPIC BeadChip. Data was mainly preprocessed and analyzed with R/Bioconductor packages.
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Project description:Background: Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathological, and molecular analyses, little is currently known about the global gene expression changes accompanying their formation. Results: To characterize the molecular processes underlying the transformation of normal colonic epithelium, we compared the transcriptomes of 32 prospectively collected adenomas with those of normal mucosa from the same individuals. Important differences emerged not only between the expression profiles of normal and adenomatous tissues, but also between those of small and large adenomas. A key feature of the transformation process was the remodeling of the Wnt pathway reflected in patent over- and underexpression of 78 known components of this signaling cascade. Conclusions: Our transcriptomic profiles of normal colonic mucosa and colorectal adenomas shed new light on the early stages of colorectal tumorigenesis. Experiment Overall Design: Pedunculated, sporadic colorectal polyps and corresponding normal mucosa were obtained during colonoscopies. The tissues were collected prospectively with informed patient consent and the approval of the local Human Research Ethics Committee.
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Project description:The genome-wide profiling of 5-hydroxymethylcytosine (5hmC) on circulating cell-free DNA (cfDNA) has revealed promising biomarkers for a variety of diseases. The purpose of our study is to investigate if 5hmC profiles from serum cfDNA are novel predictive biomarkers for the development of chemoresistance in high-grade serous ovarian cancer (HGSOC). We hypothesized that 5-hmC profiles associate with the development of chemoresistance and elucidate pathways that may drive chemoresistance in HGSOC. We developed a novel multivariate model based on clinico-pathologic data and a cfDNA-derived 5hmC-annotated gene that can predict response to platinum-based chemotherapy in intermediate-sensitive HGSOC. These results merit further investigation of our model as a predictive model.
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Project description:As a non-invasive blood testing, the detection of cell-free DNA (cfDNA) methylation in plasma is raising increasing interest due to its diagnostic and biology applications. Although extensively used in cfDNA methylation analysis, bisulfite sequencing is less cost-effective. Through enriching methylated cfDNA fragments with MeDIP followed by deep sequencing, we aimed to characterize cfDNA methylome in cancer patients. In this study, we investigated the cfDNA methylation patterns in lung cancer patients by MeDIP-seq. MEDIPS package was used for the identification of differentially methylated regions (DMRs) between patients and normal ones. Overall, we identified 330 differentially methylated regions (DMRs) in gene promoter regions, 33 hypermethylation and 297 hypomethylation respectively, by comparing lung cancer patients and healthy individuals as controls. The 33 hypermethylation regions represent 32 genes. Some of the genes had been previously reported to be associated with lung cancers, such as GAS7, AQP10, HLF, CHRNA9 and HOPX. Taken together, our study provided an alternative method of cfDNA methylation analysis in lung cancer patients with potential clinical applications.
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