Circulating tumour cells signal more aggressive HCC

Circulating tumour cells (CTCs) are more frequently detected in peripheral blood samples of patients with more advanced than early-stage hepatocellular carcinoma (HCC), according to a study presented at the recently concluded Asian Pacific Digestive Week 2021 (APDW 2021).

“In the future, CTCs may be [used as] potential markers of HCC aggressiveness, which could guide staging and prognosis,” said lead study author Dr Thaninee Prasoppokakorn, from the Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital.

The single-centre, cross-sectional analysis included 73 HCC patients (mean age 60±12 years, 77 percent men) from whom 8-mL peripheral blood samples were collected. CTCs were detected using fluorescent microscopy. Signals for the MUC1 and EpCAM proteins were used as indicators of CTC presence.

According to the Barcelona-Clinic Liver Cancer (BCLC) staging system, most patients had early-stage HCC (stage A; n=26, 36 percent), followed closely by stages C (n=25, 34 percent) and B (n=22, 30 percent). Across all disease stages, the overall CTC detection rate was 79.5 percent (n=58 of 73). [APDW 2021, abstract OPP-0041]

Stratifying according to BCLC class showed that the rate of CTC positivity was positively correlated with tumour stage, increasing from 65.4 percent in the stage A samples to 77.3 percent and 96 percent in stages B and C, respectively (p=0.02).

The same pattern was reflected in mean CTCs, which increased from 2.5±3.5 to 10.0±16.8 and 50.8±140.1 cells/8-mL in BCLC stages A, B, and C, respectively, with borderline significance (p=0.09).

Looking at other indicators of disease severity further confirmed that CTC numbers were higher in patients with more vs less aggressive HCCs, though significance was not achieved. For instance, those with vascular invasion had a mean count of 44.44±138.55 cells/8-mL as opposed to 9.27±25.31 cells/8-mL in those without such marker (p=0.22).

Similarly, CTC was elevated in those with vs without lymph node (87.8±205.89 vs 9.72±22.78 cells/8-mL; p=0.24) or distant (214.25±326.26 vs 10.22±22.61 cells/8-mL; p=0.30) metastases.

CTC counts could also serve as indicators of poor HCC prognosis, according to receiver operator characteristic (ROC) curve analysis. The areas under the curve for predicting vascular invasion, BCLC stage C disease, and lymph and distant metastases were 0.72 (p=0.02), 0.75 (p<0.01), 0.69 (p=0.04), and 0.80 (p=0.04), respectively.

CTCs are neoplastic cells released from the primary tumour into the blood circulation, acting as markers for disease progression and metastasis, explained Prasoppokakorn. Measuring CTCs could help “facilitate treatment decision and monitor treatment response and disease recurrence.”

“This study is a pilot study that demonstrates that advanced HCC patients have higher detection rate of peripheral CTC positivity, with [the tendency] to have a higher number of CTCs than those with early-stage [disease],” she added.