Dataset Information

Altered cfDNA fragmentation profile in hypomethylated regions as diagnostic markers in breast cancer.

ABSTRACT:

Background

Breast cancer, the most common malignancy in women worldwide, has been proven to have both altered plasma cell-free DNA (cfDNA) methylation and fragmentation profiles. Nevertheless, simultaneously detecting both of them for breast cancer diagnosis has never been reported. Moreover, although fragmentation pattern of cfDNA is determined by nuclease digestion of chromatin, structure of which may be affected by DNA methylation, whether cfDNA methylation and fragmentation are biologically related or not still remains unclear.

Methods

Improved cfMeDIP-seq were utilized to characterize both cfDNA methylation and fragmentation profiles in 49 plasma samples from both healthy individuals and patients with breast cancer. The feasibility of using cfDNA fragmentation profile in hypo- and hypermethylated regions as diagnostic markers for breast cancer was evaluated.

Results

Mean size of cfDNA fragments (100-220 bp) mapped to hypomethylated regions decreased more in patients with breast cancer (4.60 bp, 172.33 to 167.73 bp) than in healthy individuals (2.87 bp, 174.54 to 171.67 bp). Furthermore, proportion of short cfDNA fragments (100-150 bp) in hypomethylated regions when compared with it in hypermethylated regions was found to increase more in patients with breast cancer in two independent discovery cohort. The feasibility of using abnormality of short cfDNA fragments ratio in hypomethylated genomic regions for breast cancer diagnosis in validation cohort was evaluated. 7 out of 11 patients were detected as having breast cancer (63.6% sensitivity), whereas no healthy individuals were mis-detected (100% specificity).

Conclusion

We identified enriched short cfDNA fragments after 5mC-immunoprecipitation (IP) in patients with breast cancer, and demonstrated the enriched short cfDNA fragments might originated from hypomethylated genomic regions. Furthermore, we proved the feasibility of using differentially methylated regions (DMRs)-dependent cfDNA fragmentation profile for breast cancer diagnosis.

SUBMITTER: Wang J

PROVIDER: S-EPMC10517480 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Altered cfDNA fragmentation profile in hypomethylated regions as diagnostic markers in breast cancer.

Wang Jun J Niu Yanqin Y Yang Ming M Shu Lirong L Wang Hongxian H Wu Xiaoqian X He Yaqin Y Chen Peng P Zhong Guocheng G Tang Zhixiong Z Zhang Shasha S Guo Qianwen Q Wang Yun Y Yu Li L Gou Deming D

Epigenetics & chromatin 20230923 1

<h4>Background</h4>Breast cancer, the most common malignancy in women worldwide, has been proven to have both altered plasma cell-free DNA (cfDNA) methylation and fragmentation profiles. Nevertheless, simultaneously detecting both of them for breast cancer diagnosis has never been reported. Moreover, although fragmentation pattern of cfDNA is determined by nuclease digestion of chromatin, structure of which may be affected by DNA methylation, whether cfDNA methylation and fragmentation are biolo ...[more]

PMID: 37740218

Similar Datasets

Project description:Due to the lack of sensitive diagnostic biomarkers for osteoporosis (OP), there is an urgent need to identify and uncover biomarkers associated with the disease in order to facilitate early clinical diagnosis and effective intervention strategies. GEO2R was employed to conduct a screening of differentially expressed genes (DEGs) within the transcriptome sequencing data obtained from blood samples of OP patients within the GSE163849 dataset. Subsequently, we conducted expression confirmation of the identified DEGs using an additional dataset, GSE35959. To further explore Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, MicroRNA (miRNA) interactions, and drug predictions, we employed the DAVID, miRTarBase, and DrugBank databases. For validation purposes, clinical OP samples paired with normal controls were collected from the Pakistani population. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression levels of DEGs and miRNA, while targeted bisulfite sequencing (bisulfite-seq) analysis was used to investigate methylation patterns. DNA and RNA from clinical OP and normal control samples were extracted using appropriate methods. Out of total identified 269 DEGs, EGFR (epidermal growth factor receptor), HMOX1 (heme oxygenase-1), PGR (progesterone receptor), CXCL10 (C-X-C motif chemokine ligand 10), CCL5 (C-C motif chemokine ligand 5), and IL12B (interleukin 12B) were prioritized as top DEGs in OP patients. Expression validation of these genes on additional Gene Expression Omnibus (GEO) dataset and Pakistani OP patients revealed consistent significant up-regulation of these genes in OP patients. Receiver operating characteristic (ROC) analysis demonstrated that these DEGs displayed considerable diagnostic accuracy for detecting OP. Targeted bisulfite-seq analysis further revealed that EGFR, HMOX1, PGR, CXCL10, CCL5, and IL12B were hypomethylated in OP patients. Moreover, has-miR-27a-5p, a common expression regulator of the EGFR, HMOX1, PGR, CXCL10, CCL5, and IL12B was also significantly down-regulated in OP patients. The DEGs that have been identified hold significant potential for the future development of diagnostic and treatment approaches for OP in preclinical and clinical applications.

Dataset Information

Altered cfDNA fragmentation profile in hypomethylated regions as diagnostic markers in breast cancer.

Background

Methods

Results

Conclusion

Publications

Altered cfDNA fragmentation profile in hypomethylated regions as diagnostic markers in breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets