Doctors have long struggled to diagnose and monitor FLC partially because no blood tests (biomarkers) work reliably for it. Standard liver cancer markers like alpha-fetoprotein (AFP) are almost always normal in FLC.
This study reports a new and promising discovery: procalcitonin (PCT), a blood marker normally used to detect bacterial infections, turns out to be highly elevated in most patients with FLC and could serve as both a diagnostic and treatment‑monitoring biomarker.
Key findings of the study
- Procalcitonin levels are unusually high in patients with FLC.
- Based on the analysis of data from two independent patient groups (Europe and the U.S.), 83% of people with FLC had elevated PCT, far higher than infection-related levels.
- In contrast, only about 3% of people with other liver cancers (classic HCC or cholangiocarcinoma) had high PCT.
- FLC tumors produce procalcitonin.
- RNA sequencing showed the gene that produces PCT (CALCA) is highly overexpressed in FLC, not in other liver tumors.
- Spatial transcriptomics confirmed that CALCA is active specifically in tumor cells that carry the FLC fusion gene (DNAJB1‑PRKACA).
- Immunohistochemistry (protein staining) found PCT protein inside tumor cells in 77% of FLC cases, and 0% of other liver cancers.
- In four patients with repeated PCT measurements, changes in PCT levels correlated with tumor response. This suggests PCT could be a simple blood test to monitor treatment efficacy.
- When tumors shrank in response to therapy, PCT dropped.
- When tumors grew or progressed, PCT rose.
Implications
FLC has no reliable blood biomarker today. Most patients with metastatic FLC have dramatically elevated PCT levels, and these levels rise and fall with treatment response. Because FLC tumors themselves produce PCT, PCT testing could potentially serve as both a diagnostic tool and a monitoring tool for the disease.
The preprint of the full article can be accessed here.
This effort was partially funded by FCF.