Deconstructing Circulating Tumor Cells in Hepatocellular Carcinoma
Provide actionable signals for liver cancer patients to receive early warning, monitor treatment efficacy, and assess the risk of recurrence.
Free cancer support
In an era of rapid medical progress, the way we detect and treat cancer is evolving dramatically. For liver cancer (hepatocellular carcinoma, HCC) patients, early detection and accurate disease monitoring can literally be the difference between life and death. Traditional tools such as ultrasound, AFP levels, and contrast-enhanced imaging, while widely used, have clear limitations. This is why scientists have been racing to develop the next generation of blood-based tests — and circulating tumor cells (CTCs), a cornerstone of liquid biopsy, are quietly revolutionizing how we understand and manage liver cancer.
Why Do We Need Better Blood Tests?
Patients’ greatest fear is often “Will my cancer be found too late?” Current methods fall short:
- Ultrasound detects only ~45% of early HCC — more than half of small tumors are missed.
- AFP is negative in 41.5% of even advanced cases.
These gaps drive the urgent search for more sensitive markers. Liquid biopsy — using CTCs, circulating tumor DNA (ctDNA), and circulating mRNA — offers a far more comprehensive and dynamic picture when combined with conventional imaging.
- CTCs: actual intact cancer cells in the blood — carry full genetic and phenotypic information
- ctDNA: tumor-derived DNA fragments released upon cell death — excellent for mutation profiling
- circulating mRNA: reflects real-time gene expression and tumor activity
This article focuses on CTCs because they provide not only detection but also functional insights that directly predict disease behavior.
The Three Pillars of Liquid Biopsy in Liver Cancer
How Do Liver Cancer Cells End Up in the Blood?
When normal hepatocytes turn malignant, they often overexpress EpCAM (epithelial cell adhesion molecule) on their surface. This marker allows scientists to “tag and capture” CTCs from a simple blood sample.
Clinical studies show that EpCAM-high HCC cells are more aggressive. In one landmark experiment, EpCAM-high CTCs isolated from a 57-year-old patient with hepatitis B-related HCC were injected into mice and grew much larger, more invasive tumors — proving these circulating cells are biologically potent and not just inert debris.
Patients whose tumors contain more EpCAM-high cells consistently show shorter survival and poorer treatment response, making CTCs a powerful prognostic biomarker.
Can CTCs Really Form New Tumors?
Some Patients Doubt This Some patients wonder: “Don’t most cancer cells die quickly in the bloodstream?” Animal evidence says otherwise. Researchers drew 30 mL of blood from HCC patients, isolated CTCs, and found that as few as 200 CTCs injected into immunodeficient mice were sufficient to generate new tumors. EpCAM-high CTCs produced significantly larger and more malignant growths.
This proves that at least a subset of CTCs are fully capable of seeding metastases and driving recurrence.
CTC Distribution Across Different Patient Groups
- Healthy individuals & cirrhosis patients: usually 0–<5 CTCs (often undetectable
- Early-stage HCC: 75–83.6% of patients have detectable CTCs
- Advanced HCC: 96.2–96.5% positivity
Detection rates rise with disease stage, highlighting CTCs’ value in both early diagnosis and staging.
Proven Clinical Applications of CTCs in Liver Cancer
3. Liver Transplantation
In a study of 193 patients, the recurrence rate was only 6.7% in patients who were negative for tumor cells (CTCs) both before and after transplantation. Conversely, if CTCs remained positive both before and after surgery, the risk of recurrence was as high as 50%. Furthermore, some cases show that an increase in the number of CTCs can predict recurrence 7 months earlier than AFP and contrast imaging. (Xu et al., 2021)4. Ablation Therapy
Ablation therapy destroys tumor tissue using heat, but studies have found that patients with positive CTCs have a 2.5 times higher risk of recurrence than those with negative CTCs. This means that CTCs can serve as an important auxiliary tool for post-ablation monitoring. (Liu et al., 2019)5. Radiation Therapy
Collaborative research with universities has demonstrated that comparing the number of central cytokines (CTCs) before and after radiotherapy provides a more sensitive reflection of treatment efficacy, with accuracy even exceeding that of amphotericin B (AFP). This makes CTCs an ideal method for real-time monitoring of radiotherapy response. (Zhang et al., 2022)6. Transarterial Chemoembolization (TACE)
A clinical study of 89 patients found that patients with high levels of CTCs had a 3.7 times higher risk of deterioration than those with low levels. This highlights the importance of CTCs as a crucial parameter for assessing efficacy and prognosis in TACE treatment. (Chen et al., 2021)Conclusion: What This Means for Patients Today and Tomorrow
For liver cancer patients, CTC testing fills critical gaps left by ultrasound and AFP. It detects recurrence and metastasis risk earlier, monitors treatment response in real time, and often outperforms traditional markers.
While challenges remain (higher sensitivity and standardization are still needed), the evidence is overwhelming: CTCs are already delivering tangible clinical value.
When combined with genomic profiling in the near future, CTC analysis will enable truly personalized treatment strategies — choosing the right therapy, at the right time, for the right patient.
For patients, understanding this technology isn’t just about hope — it’s about having informed, deeper conversations with your oncologist and making smarter decisions for your own survival.
Want to know how to choose the most suitable adjuvant therapy for cancer?
Contact our professional team now
References
- Chen, J., et al. (2021). Clinical significance of circulating tumor cells in hepatocellular carcinoma: A meta-analysis. Journal of Hepatology, 74(3), 533–545.
- Hsu, W., Liu, C., & Huang, Y. (2024). Liquid biopsy in hepatocellular carcinoma: Clinical applications and future perspectives. Cancers, 16(2), 312.
- Liu, X., et al. (2019). Circulating tumor cells as prognostic and predictive markers for recurrence after radiofrequency ablation in hepatocellular carcinoma. Oncotarget, 10(12), 1124–1133.
- Marrinucci, D., et al. (2012). Case study of circulating tumor cells in hepatocellular carcinoma. Clinical Cancer Research, 18(20), 5751–5759.
- Sun, Y., et al. (2020). Prognostic significance of circulating tumor cells in patients with hepatocellular carcinoma undergoing surgical resection. Annals of Surgical Oncology, 27(2), 736–744.
- Wang, S., & Zhang, J. (2020). Advances in early detection of hepatocellular carcinoma: From ultrasound to liquid biopsy. Hepatology International, 14(6), 771–783.
- Xu, W., et al. (2021). Circulating tumor cells and recurrence in hepatocellular carcinoma patients after liver transplantation. Liver Transplantation, 27(4), 575–586.
- Zhang, L., et al. (2021). EpCAM expression in hepatocellular carcinoma: Clinical relevance and implications for circulating tumor cell detection. Theranostics, 11(10), 4833–4846.
- Zhang, Y., et al. (2022). Monitoring circulating tumor cells for response assessment in radiotherapy of hepatocellular carcinoma. Frontiers in Oncology, 12, 845312.
- Zhu, X., et al. (2020). Detection and significance of circulating tumor cells in hepatocellular carcinoma. Cancer Letters, 475, 1–9.