Plasma hPG₈₀ (Circulating Progastrin) as a Novel Prognostic Biomarker for Hepatocellular Carcinoma

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. In this study, we evaluated the prognostic value of plasma hPG₈₀ in patients with HCC, alone or in combination with AFP. A total of 168 HCC patients were tested prospectively for hPG₈₀ and analyzed retrospectively. The prognostic impact of hPG₈₀ and AFP levels on patient survival was assessed using Kaplan-Meier curves and log-rank tests. hPG₈₀ was detected in 84% of HCC patients. There was no correlation between hPG₈₀ and AFP levels in the training and validation cohorts. Both cohorts showed higher sensitivity of hPG₈₀ compared to AFP, especially at early stages. Patients with high hPG₈₀ (hPG₈₀+) levels (optimal cutoff value 4.5 pM) had significantly lower median overall survival (OS) compared to patients with low hPG₈₀ (hPG₈₀-) levels (12.4 months versus not reached respectively, p < 0.0001). Further stratification by combining hPG₈₀ and AFP levels (cutoff 100 ng/mL) improved prognosis in particular for those patients with low AFP level (hPG₈₀-/AFP+ and hPG₈₀-/AFP-, 13.4 months versus not reached respectively, p < 0.0001 and hPG₈₀+/AFP+ and hPG₈₀+/AFP-, 5.7 versus 26 months respectively, p < 0.0001). This was corroborated when analyses were performed using the BCLC staging especially at early stages. Our findings show that hPG₈₀ could serve as a new prognostic biomarker in HCC. Used in combination with AFP, it improves the stratification of the patients in good and poor prognosis, especially for those patients with negative AFP and early-stage HCC.