The Role of Molecular Diagnostics in Preventive Medicine
Cancer remains a global public health problem with a high mortality rate, as most patients are diagnosed at advanced stages. This makes treatment more complex and less effective. Early detection of cancer is therefore critical to improving survival rates and patient quality of life.
Circulating Tumor DNA (ctDNA), fragments of DNA released into the bloodstream by tumor cells, has emerged as a promising biomarker for multi-cancer screening. With the support of Next-Generation Sequencing (NGS) technology, ctDNA testing demonstrates high sensitivity and specificity. This article aims to describe the principles, significance, advantages, limitations, and potential of ctDNA as a preventive diagnostic tool for early-stage cancer.
Cancer as a Global Burden
Cancer continues to be one of the leading causes of death worldwide. The World Health Organization (WHO) projects that cancer-related mortality will increase by more than 45% by 2030. Notably, about 70% of patients are typically diagnosed at advanced stages, which correlates with a significant decrease in survival rates. Thus, the development of diagnostic methods capable of detecting cancer at an early stage is essential.
Unlocking Cancer Detection with Circulating Tumor DNA
Circulating Tumor DNA (ctDNA) refers to genetic fragments shed by cancer cells into the bloodstream. ctDNA testing is classified as a type of liquid biopsy, which aims to identify DNA fragments released by tumor cells into body fluids, particularly blood. This method is minimally invasive, requiring only a simple blood draw.
By employing Next-Generation Sequencing (NGS), ctDNA testing allows for the simultaneous detection of genetic mutations associated with multiple cancer types. This technique reduces the need for traditional tissue biopsies, which often involve surgery or direct tissue sampling.
General Process of ctDNA Testing
- Blood Collection: Approximately 10 mL of blood is collected from the patient.
- Plasma Separation: Plasma is isolated from whole blood, followed by ctDNA extraction.
- Genomic Analysis: High-resolution sequencing using NGS is performed to detect:
- Multiple gene mutations simultaneously (multi-gene analysis)
- Novel mutations potentially linked to carcinogenesis
- Treatment response and monitoring of drug resistance during therapy
The analysis ultimately identifies cancer-related mutations and their specific types, aiding in the formulation of personalized treatment strategies.
Spectrum of Detectable Malignancies
ctDNA testing can detect risks for at least 10 common cancers, including:
- Lung cancer
- Breast cancer
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma and cholangiocarcinoma
- Pancreatic cancer
- Ovarian cancer
- Esophageal cancer
- Endometrial cancer
- Head and neck cancer
Advantages and Performance
- Sensitivity: 78.1%
- Specificity: 95.9%
- Minimally invasive: Requires only a single blood draw
- Rapid results: Turnaround time within 30 days
- Multi-cancer detection: Ability to detect risks of multiple tumor types simultaneously
Suitable Candidates for ctDNA Testing
- Individuals aged 40 and above, who are at increased risk of cancer with age, even without symptoms
- Those with a family history of cancer
- Individuals with high-risk behaviors (e.g., smoking, alcohol consumption, exposure to environmental carcinogens, PM2.5 pollution)
- Adults aged 18 years and above seeking preventive health screening
- Patients unwilling to undergo or unsuitable for tissue biopsy
Limitations and Considerations
Despite its high potential, ctDNA testing has important limitations:
- Applicable only for individuals not previously diagnosed with cancer
- Cannot fully replace histopathological diagnosis
- Results must be interpreted alongside clinical data and individual risk factors
ctDNA as a Pillar of Precision Oncology
ctDNA testing is increasingly recognized as an innovative approach in precision oncology, enabling early cancer detection while reducing the need for invasive procedures such as surgical biopsies. Integrating this technology into routine health checkups enhances preventive cancer screening and may help reduce the long-term economic burden of healthcare systems.
As a novel diagnostic innovation in preventive medicine, ctDNA testing holds strong potential to improve patient survival, reduce costs, and significantly enhance overall quality of life.
References
- World Health Organization. Global cancer observatory. Geneva: WHO; 2023.
- Wan JCM, Massie C, Garcia-Corbacho J, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223–238.
- Cohen JD, Li L, Wang Y, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. 2018;359(6378):926–930.
