PURPOSE: Our aims are to determine levels of circulating cellular and protein biomarkers in hepatocellular carcinoma (HCC) patients and to analyse any relationships with clinical parameters.
METHODS: Fifty-four consenting patients were recruited. Circulating tumour cells (CTCs) were enumerated (by CellSearch) and characterised via filtration [by isolation by size of epithelial tumour cells (ISET)] with downstream immunohistochemistry (IHC). Glypican-3 (GPC3) expression in tumour biopsies and CTCs (by IHC) was compared, and levels of circulating caspase-cleaved and full-length cytokeratin 18 (CK18, measured using M30 and M65 ELISAs) were examined as a putative prognostic factor and marker of tumour burden.
RESULTS: CTCs were identified in 14 out of 50 (28%) patients by CellSearch and in 19 out of 19 (100%) patients by ISET. The presence of GPC3-positive CTCs by ISET was 100% concordant with the presence of GPC3-positive cells in the original tumour (n = 5). No statistically significant correlations were observed between CTC number and clinical characteristics, although trends were noted between CTC subtypes, Child-Pugh score and tumour node metastasis stage. Serum M30 and M65 levels (as continuous variables) significantly correlated with overall survival (OS) in a univariate analysis (p = 0.003 and p < 0.001, respectively); M65 levels remained statistically significant in a multivariate analysis (p = 0.029).
CONCLUSIONS: This is the first study to detect GPC3-positive CTCs in HCC, important for drug development with this target. The significant association of circulating CK18 with OS in HCC further exemplifies the utility of circulating biomarkers in cancer.
- Aged, 80 and over
- Biomarkers, Tumor/blood
- Carcinoma, Hepatocellular/blood
- Cell Separation
- Follow-Up Studies
- Immunoenzyme Techniques
- Liver Neoplasms/blood
- Middle Aged
- Neoplasm Staging
- Neoplastic Cells, Circulating/pathology
- Circulating tumour cells (CTCs)
- Hepatocellular carcinoma (HCC)
- Cytokeratin 18 (CK18)
- Prognostic biomarker
- Glypican-3 (GPC3)