Plasma hPG₈₀ (circulating progastrin) as a novel prognostic biomarker for hepatocellular carcinoma at early to intermediate stages (BCLC 0 to B).

Abstract

472 Background: Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis. However, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers including HCC, even at early stages. In this study, we evaluated the prognostic value of plasma hPG80 in patients with HCC at early and intermediate stages. Methods: A total of 79 HCC patients including 44 BCLC from 0 to A and 35 BCLC B managed with local or systemic treatments, (“Liverpool” biobank) were enrolled prospectively and analyzed retrospectively. hPG80 was quantified using DxPG80 Lab kit (ECS-Progastrin) with a limit of detection at 1 pM and AFP was quantified using Cobas E411 in the blood of HCC patients. An optimal cutoff value of hPG80 was identified at 4.5 pM by calculating the minimal p-value based on the log-rank method. For AFP, a cutoff of 100 ng/mL was used as for liver transplantation (Notarpaolo, 2016). The prognostic impact of hPG80 and AFP levels on patient overall survival (OS) was assessed using Kaplan-Meier curves and log-rank tests. Results: hPG80 was detected in 36 of 44 (81.8%) HCC patients at stages BCLC 0 to A and 29 of 35 (82.9%) at stage BCLC B by contrast to AFP present in only 5 (11.4%) and 9 (25.7%) patients respectively. The median of hPG80 was 5.7 pM (IQR: 1.7-22.4 pM) at stages BCLC 0 to A, 6.0 pM (IQR: 1.5-22.2 pM) at stage BCLC B and significantly different from a non-HCC age-range matched control group cohort (median value: 1.5 pM, IQR 0.6-3.2 pM, p < 0.0001). When combining BCLC 0 to B, the median OS for hPG80+ patients (n = 46) was significantly shorter than that of hPG80- patients (n = 33) (25 months versus undefined, HR: 3.07, 95% CI: 1.46-6.43; p = 0.0064). AFP+ patients were also significantly correlated with poorer OS (17.5 months versus undefined, HR: 3.16, 95% CI: 1.06-9.47; p = 0.0030). Then, we evaluated the prognostic significance of hPG80 in combination with AFP levels. hPG80+ patients with AFP > 100 ng/mL (n = 46) had a worse OS than that of patients with AFP < 100 ng/mL patients (n = 33) (15.8 months versus undefined, HR: 6.38, 95% CI: 1.74-23.41; p = 0.0052). Conclusions: Our findings show that hPG80 could serve as a new prognostic biomarker for HCC patients at early to intermediate stages. These results will need to be confirmed in a prospective study, but it opens the possibility to use hPG80 as a biomarker for HCC patients at early stage at a time they can be treated to be cured.