Editor’s Note: Liquid biopsy is a cutting-edge technology that utilizes molecular biomarkers in human body fluids for analysis, thereby obtaining relevant disease information. In the era of precision medicine, liquid biopsy has become an indispensable tool in the field of tumor diagnosis and treatment. It has received extensive attention and research for its applications in early tumor screening, treatment plan selection, disease recurrence monitoring, and biopharmaceuticals. Notably, plasma free DNA fragmentomics, as an emerging technology in the field of liquid biopsy, is increasingly applied in the diagnosis of various cancers.
At the 2024 Greater Bay Area Hepatology International Forum and the Conference on the Elimination of Viral Hepatitis, Professor Yuming Lu , an academician of the Chinese Academy of Sciences and the Vice Dean of the Faculty of Medicine at The Chinese University of Hong Kong, delivered an exciting report titled “The Application of Plasma DNA Fragmentomics in Liquid Biopsy”. Our journal had the honor of inviting Academician Yuming Lu to provide a detailed explanation of the applications, advantages, and future prospects of liquid biopsy in cancer early screening.
What role does plasma DNA fragmentomics play in liquid biopsy, and how can it help doctors accurately diagnose diseases like cancer at an early stage?
Academician Yuming Lu : Plasma DNA fragmentomics plays a crucial role in liquid biopsy. Traditional liquid biopsy samples include blood, saliva, urine, cerebrospinal fluid, and pleural effusion, primarily detecting DNA in plasma to find clues about cancer. However, due to the limited number of mutations in the cancer cell genome, not all DNA fragments can signal cancer. Plasma DNA fragmentomics offers a new perspective.
DNA fragmentomics focuses on the patterns of DNA breaks within cells. In cancer patients, these break patterns differ from those in healthy individuals. Each type of DNA fragment has a unique break pattern, which gives fragmentomics potential value in liquid biopsy. By studying these patterns in-depth, we can more accurately identify cancer-related DNA fragments, thereby enhancing the sensitivity and specificity of liquid biopsies.
Furthermore, liquid biopsy technologies based on DNA fragmentomics significantly reduce the cost of tumor screening, improve accessibility, and require only a small blood sample with a simple process and affordable end-user price. This makes it possible for more patients to benefit from this advanced diagnostic method.
In the context of early cancer screening, liquid biopsy technologies have significant advantages over traditional tumor markers such as alpha-fetoprotein (AFP) for liver cancer and prostate-specific antigen (PSA) for prostate cancer.
Traditional tumor markers like AFP and PSA, although their levels can rise due to cancer, are not necessarily linked directly to the cancer process. These markers can be influenced by various factors, including inflammation, infection, or other non-cancerous conditions, which means they have relatively low specificity and could lead to misdiagnosis or missed diagnoses.
In contrast, liquid biopsy technologies analyze DNA fragments in the plasma, allowing for the direct detection of cancer-related genetic mutations or epigenetic changes. These changes are direct causes of cancer, thus liquid biopsy technologies provide higher accuracy and specificity. By deeply analyzing the patterns of DNA fragmentation, we can more precisely identify cancer-related DNA fragments, thereby improving the sensitivity and reliability of early cancer screening.
What does the future hold for liquid biopsy and early cancer screening? Are there any potential technological breakthroughs or research directions that could further advance this field and bring greater benefits to patients?
In cancer screening, there are primarily two approaches to liquid biopsy: one is targeted screening for specific cancers, and the other is early detection of multiple types of cancers.
The former has already shown significant effectiveness in certain types of cancer, such as screening for nasopharyngeal carcinoma. Using plasma DNA technology, we can detect nasopharyngeal carcinoma much earlier, and these patients’ survival rates are ten times higher than those detected through conventional screening methods. Guangdong has the highest incidence of nasopharyngeal carcinoma globally, and if this technology can be widely adopted in the Greater Bay Area, it could significantly reduce the mortality rate of nasopharyngeal carcinoma in China. We should also continue to explore the application of the same technology in early screening for other cancers such as liver and prostate cancer.
Early detection of multiple cancers is another important research direction. Technically, we have the capability to perform screening for multiple cancers. However, because this involves various cancers, clinical trials require a large sample size, are costly, and proving a survival rate advantage is more challenging. Therefore, the development in this area may take longer.
Overall, I am confident in the application of liquid biopsy in early cancer screening. Through continuous technological innovation and the expansion of research directions, the fields of liquid biopsy and early cancer screening hold promise to provide stronger support for the early detection and treatment of cancer, offering greater survival benefits to patients.
