Researchers from the Dalian Institute of Chemical Physics, Chinese Academy of Sciences, in collaboration with Professor Qi Wang from the Second Affiliated Hospital of Dalian Medical University and Professor Jinghua Chen from Jiangnan University, have made a breakthrough in the early diagnosis of liver cancer based on circulating tumor cells (CTCs). By combining affinity ligands with highly selective binding to target sugar chains, precise shape and size matching using cell imprinting polymers, and good biocompatibility, the team has developed a novel cell imprint hydrogel material. This material enables the precise capture and non-destructive release of CTCs from peripheral blood, potentially advancing early diagnosis of liver cancer and single-cell multi-omics analysis. The research findings have been published in "Advanced Materials."
According to statistics, there are 906,000 new liver cancer cases diagnosed globally each year, with 830,000 deaths, of which China accounts for 45% and 47% respectively. One major reason for the low survival rate of liver cancer is the high cost of screening and the dull pain sensation of the liver, leading to most patients being diagnosed in the middle to late stages, missing the optimal treatment window. The serum biomarker alpha-fetoprotein (AFP) is currently used in clinical detection for liver cancer screening, diagnosis, recurrence risk assessment, and treatment efficacy observation. However, AFP has low sensitivity, resulting in many false negative cases among patients with low AFP levels.
CTCs in peripheral blood, carrying genetic and epigenetic information of tumor tissues, are recognized as the gold standard in liquid biopsy. However, with only 0 to 3 CTCs per milliliter of blood, detection results are easily affected by the complex blood environment, and CTCs are prone to damage during capture and processing.
In this study, the research team prepared a PP-co-AHH+ hydrogel with low swelling ratio, good compressibility, excellent reversibility, good blood and cell compatibility, strong anti-fouling ability, and clear cell imprints targeting the sialic acid polysaccharides on the surface of CTCs. The capture efficiency of this hydrogel reached 93% when evaluating 10 CTCs. Importantly, the captured CTCs can be released using trypsin solution while maintaining high cell viability, which is crucial for single-cell multi-omics analysis.
Furthermore, the team conducted CTC capture tests on 100 human samples. The results showed that CTC counting had a 90% accuracy in distinguishing between liver cancer, liver cirrhosis, and healthy individuals. By combining AFP, CTCs, and natural killer cell results, the testing accuracy was increased to 94%, with a sensitivity of 90%, meeting the requirements of clinical testing. Additionally, the hydrogel material can be reused up to ten times, with a capture cost of only 50 yuan per sample, significantly lower than the hospital price of 3500 yuan. Moreover, this hydrogel material can obtain high-purity, highly active CTCs from patient blood, facilitating seamless integration with downstream single-cell multi-omics analysis to advance precise treatment of liver cancer.
The newly developed cell imprint hydrogel in this study holds promise as a tool for early diagnosis of liver cancer.
For more information, refer to the research paper at: https://doi.org/10.1002/adma.202402379
