Groundbreaking High-Throughput Methylation-Based Non-Invasive Detection Technology Enables Early Cancer Screening and Tissue-of-Origin Tracing

A week ago, Professor Kun Zhang of the University of California, San Diego, published a commentary in Nature Methods, reviewing the latest global advances in single-cell analysis methods. Yesterday, Professor Zhang’s team unveiled their latest breakthrough in Nature Genetics: a world-first high-throughput, non-invasive methylation detection technology, which holds promise for non-invasive early cancer screening and tumor origin tracing.

Detection and Localization of Cancer Using Dual Signals from Cancer Markers and Tissue-Specific CpG Methylation Patterns

Based on ctDNA in cancer patients, early detection of cancer can be performed, but these methods cannot trace the location where the tumor originated. Professor Zhang Kun stated, “Understanding the location of the tumor is crucial for effective early detection.”

To address this challenge, Professor Zhang Kun’s team has developed a novel liquid biopsy technology that not only enables early detection of cancer but also achieves tissue localization. As cancer develops in the body, it competes with normal cells for nutrients and space, leading to the death of normal cells. When these normal cells die, they release their DNA into the bloodstream, allowing researchers to identify the affected tissues through analysis of this DNA.

Since each tissue in the body has its unique methylation pattern, tissues can be localized based on this characteristic. In this new method, tissue localization is achieved by screening for CpG methylation haplotype tags.

Professor Zhang Kun said, “We stumbled upon this method by chance. Initially, we employed conventional methods with the sole aim of detecting cancer cell signals and tracing their origin. However, during this process, we also detected signals from other cell types and realized that integrating these two sets of signals could actually determine both the presence of cancer and its location.”

During the research and development process, researchers first constructed a database encompassing the complete CpG methylation profiles of ten different tissues (liver, small intestine, colon, lung, brain, kidney, pancreas, spleen, stomach, and blood). They also analyzed tumor and blood samples from cancer patients at the UCSD Moores Cancer Center and established a database of cancer-specific genetic markers.

Next, the researchers screened blood samples from cancer patients and healthy individuals to detect dual signals comprising cancer markers and tissue-specific CpG methylation patterns. The assay operates similarly to a two-factor authentication process: the detection of both signals above the statistical cutoff indicates a positive result.

Professor Zhang Kun emphasized, “This is a proof-of-concept study. To advance this research to the clinical stage, we need to collaborate with physicians to further optimize and refine this approach.”

Professor Zhang Kun’s research is undoubtedly groundbreaking. The novel combination of tumor ctDNA liquid biopsy and methylation detection will reshape our understanding of “early cancer screening,” with promising industry prospects. According to Professor Zhang, the “novel high-throughput non-invasive methylation detection technology” developed in this study has been filed for global patents and exclusively licensed to Genetron Health, a company he co-founded, for commercial development of new early cancer detection solutions. In the near future, this breakthrough may give rise to the next major player in the global early cancer screening market, while enabling more people to detect cancer at an early stage and receive timely treatment.

Source: Sequencing China

References:

Shicheng Guo, Dinh Diep, Nongluk Plongthongkum, Ho-Lim Fung, Kang Zhang and Kun Zhang. Identification of methylation haplotype blocks aids in deconvolution of heterogeneous tissue samples and tumor tissue-of-origin mapping from plasma DNA. doi:10.1038/ng.3805