Abstract
BackgroundColorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis.MethodsPeripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets.ResultsCompared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data.ConclusionsMeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer.
Highlights
Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide
Whole‐genome MeDIP‐seq analysis of cell-free DNA (cfDNA) Plasma was collected from colorectal cancer patients (n = 4) and healthy controls (n = 3) for analysis in this study
The clinicopathological information of the patients is shown in Table 1. cfDNA was extracted from plasma using the QIAamp Circulating Nucleic Acid Kit
Summary
Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide [1,2,3]. Diagnosis and treatment for colorectal cancer are crucial and often confer a good prognosis [4]. Colonoscopy is currently a common method of detecting colorectal cancer [5, 6]. The fecal occult blood test (FOBT) is the most widely used method for colorectal cancer screening, but its sensitivity for the early detection of colorectal cancer is low [8]. There are still many obstacles to the early diagnosis of colorectal cancer. If a novel biomarker can be developed for the early detection of colorectal cancer, it will have profound benefits for the general public
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
