【CSCO 2022 Prospect】Application value of ctDNA methylation in early diagnosis of liver cancer and bowel cancer

Cancer is one of the leading causes of
human death.
Although early screening, early diagnosis and early treatment is one of the most effective ways to improve the prognosis of cancer patients, early cancer screening is still very challenging
.
At present, clinical tumor screening methods (imaging, tumor markers, etc.
) are not completely reliable, their sensitivity is limited, and compliance is low, and for most cancer types, non-invasive cancer early screening tools are rare
.

As an emerging technology, liquid biopsy has gradually become the main technology for early tumor screening due to its convenient and fast advantages, which collects blood or other body fluids in a minimally invasive or non-invasive way and analyzes the molecular markers extracted from them, circulating tumor DNA (ctDNA), extracellular vesicles (EVs) and tumor-induced platelets (TEP).

Circulating tumor DNA (ctDNA) is an extracellular DNA present in plasma or serum, cerebrospinal fluid and other body fluids, mainly from necrotic or apoptotic tumor cells, extrosomes secreted by tumor cells and circulating tumor cells, usually 160-180bp
in size.
ctDNA is a class of cell-free DNA (cfDNA) that accounts for a low proportion (even between 0.
1% and 1%)
.

From a microscopic perspective, cancer occurs in multiple stages, involving genetic variation and epigenetic effects
.
Normal DNA methylation acts as a regulator of gene expression, embryonic development, X chromosome inactivation, and genomic imprinting, but abnormal DNA methylation and altered DNA methylation patterns are common epigenetic phenomena
in tumor cells.
Among them, 5-methylcytosine (5-mC) in the CpG island is a major epigenetic modification
.
Normally, the promoter region of the CpG island in the promoter region of normal cells is almost never methylated, but hypermethylation that occurs on the promoter of the tumor suppressor gene will cause the gene to be silenced
.
This abnormal methylation promotes tumorigenesis, which further leads to a range of genetic diseases and even cancer, suggesting that changes in DNA methylation can be used as a powerful diagnostic marker for
cancer.

Compared with the pattern of site-specific variation in ctDNA, DNA methylation occurs in almost all cancerous lesions and early stages of cancer, and 60-80% of cytosine residues are methylated at 28 million CpG double nucleotide sites in the human genome, and the enrichment of CpG islands can significantly improve the methylation signal-to-noise ratio
.
In addition, methylation modifications are distributed in clusters and are more
specific than base mutations.
Therefore, ctDNA methylation detection technology has its unique advantages
in terms of tumor detection sensitivity.

On November 6, 2022, Professor Yang Tian of the Oriental Hepatobiliary Surgery Hospital of Naval Medical University and Professor Cai Guoxiang of the Cancer Hospital of Fudan University will introduce the application value of ctDNA methylation in the early diagnosis of liver cancer and bowel cancer respectively, and we look forward to the in-depth research of ctDNA methylation in early tumor screening to benefit tumor patients
.

Resources:

https://mp.
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com/s/ki-9x0QlGJZTamLiXQ1RDg

https://mp.
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com/s/M4FPk0ru3siRNJpuwn0gSw

https://mp.
weixin.
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com/s/xoumXE0SO3x2m_d47UFy6g

https://mp.
weixin.
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com/s/Ox1vdIZBniFFkD8vwbVe2g