A Broader View of Circulating Tumor Cells in Liver Cancer
Building the analytical foundation for liquid biopsy
Hepatocellular carcinoma, or HCC, is the most common form of primary liver cancer. Disease assessment currently relies on imaging, laboratory testing and clinical evaluation. Liquid biopsy could eventually complement these approaches by providing minimally invasive access to tumor-associated information through a blood sample.
Circulating tumor cells, or CTCs, are a potentially information-rich component of liquid biopsy. However, they occur at extremely low concentrations and can differ substantially in their molecular and phenotypic characteristics. Their reliable detection and enumeration in whole blood therefore remain technically challenging.
A controlled validation in whole blood
Within the Medical Valley Award–supported QuLiBi project, Qtas and LMU Klinikum are evaluating the analytical performance of the Qtas qMRI platform in healthy-donor whole blood.
Defined numbers of cells from HCC cell lines are introduced into the blood samples as controlled CTC surrogates. Because the number and identity of the introduced cells are known, the project can systematically assess how accurately and reproducibly the platform detects rare tumor cells in a complex blood matrix.
The study includes both EpCAM-high and EpCAM-low HCC cell models. This enables the technology to be tested across a biologically relevant range of epithelial-marker expression rather than against a single, strongly EpCAM-positive cell population.
The Qtas platform uses diamond quantum sensors and wide-field magnetic resonance microscopy to detect magnetically labelled cells. Under controlled spike-in conditions, the collaboration can characterize analytical performance parameters including sensitivity, specificity, accuracy and reproducibility. The results are also benchmarked against established cell-based CTC detection and enumeration workflows.
Why EpCAM heterogeneity matters
Many established CTC technologies use the epithelial cell adhesion molecule EpCAM for cell enrichment or detection. However, tumor-cell populations are heterogeneous, and not every cell expresses EpCAM at the same level.
Cells with low EpCAM expression may therefore be recovered less efficiently by workflows that depend strongly on this marker. This is particularly relevant when a method is intended not only to identify the most strongly epithelial cells, but to provide a broader representation of heterogeneous tumor-cell populations.
By comparing EpCAM-high and EpCAM-low HCC cell models under otherwise controlled conditions, the project examines how marker expression influences rare-cell detection and whether the Qtas workflow can maintain reliable analytical performance across both phenotypes.
Preparing the next stage of HCC research
The current project focuses exclusively on analytical validation using controlled spike-in samples. It does not yet involve blood samples from HCC patients, serial blood draws or longitudinal assessment of disease and treatment response.
A successful analytical validation would establish the technical evidence needed to design separate prospective studies with patient-derived samples. These future studies could investigate the detection and molecular characterization of genuine HCC-associated CTCs, establish clinical validity and examine whether serial CTC measurements can complement imaging, laboratory markers and clinical assessment during treatment.
In this way, the present project addresses a necessary first step: demonstrating that rare HCC cell models can be detected and enumerated reliably in whole blood before the platform is evaluated as a potential tool for longitudinal monitoring in patients.
Collaboration
The project is conducted by Qtas in collaboration with Dr. Marianna Alunni-Fabbroni and Prof. Moritz Wildgruber (Department of Radiology, LMU University Hospital) and is supported by the Medical Valley Award 2024.
