5‐Hydroxymethylcytosine signature in circulating cell‐free DNA as a potential diagnostic factor for early‐stage colorectal cancer and precancerous adenoma

Autor: Shuangxiu Wu, Fuming Sun, Zewen Xiao, Xue Tao, Xiaohong Feng, Wenji Sun, Qian Cheng, Wendy Wu, Yang Yu, Shengnan Luo, Lu Zheng, Ji Tao, Zhiyuan Yun, Jiebing Tang, Gaojing Liu, Chunlong Wu, Man Li, Xiaoling Li
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Oncology
Male
Cancer Research
Colorectal cancer
0302 clinical medicine
Cluster Analysis
cell‐free DNA
Research Articles
RC254-282
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
General Medicine
DNA
Neoplasm
Middle Aged
Cell-free fetal DNA
030220 oncology & carcinogenesis
5-Methylcytosine
Molecular Medicine
Female
Colorectal Neoplasms
Cell-Free Nucleic Acids
Research Article
Adenoma
Adult
medicine.medical_specialty
precancerous adenoma
Malignancy
03 medical and health sciences
Internal medicine
Genetics
medicine
Humans
Epigenetics
KEGG
Aged
Neoplasm Staging
business.industry
Genome
Human
5‐hydroxymethylcytosine signature
Molecular Sequence Annotation
medicine.disease
Circulating Cell-Free DNA
digestive system diseases
genomic DNA
030104 developmental biology
business
Precancerous Conditions
early‐stage colorectal cancer
Zdroj: Molecular Oncology, Vol 15, Iss 1, Pp 138-150 (2021)
Molecular Oncology
ISSN: 1574-7891
1878-0261
Popis: Genome‐wide 5hmC profiling in cell‐free DNA acquired from CRC patients, adenoma patients, and healthy individuals revealed that the differential 5hmC‐modified regions were gathered into four clusters with no overlap, although there are a few overlapped genes shared between the different clusters. CRC patients with adenoma history showed exclusive 5hmC‐gain characteristics, which was consistent with the ‘parallel’ evolution hypothesis in adenoma.
Approximately 85% colorectal cancers (CRCs) are thought to evolve through the adenoma‐to‐carcinoma sequence associated with specific molecular alterations, including the 5‐hydroxymethylcytosine (5hmC) signature in circulating cell‐free DNA (cfDNA). To explore colorectal disease progression and evaluate the use of cfDNA as a potential diagnostic factor for CRC screening, here, we performed genome‐wide 5hmC profiling in plasma cfDNA and tissue genomic DNA (gDNA) acquired from 101 samples (63 plasma and 38 tissues), collected from 21 early‐stage CRC patients, 21 AD patients, and 21 healthy controls (HC). The gDNA and cfDNA 5hmC signatures identified in gene bodies and promoter regions in CRC and AD groups were compared with those in HC group. All the differential 5hmC‐modified regions (DhMRs) were gathered into four clusters: Disease‐enriched, AD‐enriched, Disease‐lost, and AD‐lost, with no overlap. AD‐related clusters, AD‐enriched and AD‐lost, displayed the unique 5hmC signals in AD patients. Disease‐enriched and Disease‐lost clusters indicated the general 5hmC changes when colorectal lesions occurred. Cancer patients with a confirmable adenoma history segmentally gathered in AD‐enriched clusters. KEGG functional enrichment and GO analyses determined distinct differential 5hmC‐modified profiles in cfDNA of HC individuals, AD, and CRC patients. All patients had comprehensive 5hmC signatures where Disease‐enriched and Disease‐lost DhMR clusters demonstrated similar epigenetic modifications, while AD‐enriched and AD‐lost DhMR clusters indicated complicated subpopulations in adenoma. Analysis of CRC patients with adenoma history showed exclusive 5hmC‐gain characteristics, consistent with the ‘parallel’ evolution hypothesis in adenoma, either developed through the adenoma‐to‐carcinoma sequence or not. These findings deepen our understanding of colorectal disease and suggest that the 5hmC modifications of different pathological subtypes (cancer patients with or without adenoma history) could be used to screen early‐stage CRC and assess adenoma malignancy with large‐scale follow‐up studies in the future.
Databáze: OpenAIRE
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