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

Abstract

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.

Plasma hPG80 (Circulating Progastrin) as a Novel Prognostic Biomarker for early-stage breast cancer in a breast cancer cohort

“…For instance, the proportion of recurrences in the low hPG 80 group was 16.3% versus 27.5% in the high hPG 80 group (data not shown). The clinical cut point identified in our study for time to recurrence (4.02 pmol/L) was similar to those found in renal cell and hepatocellular carcinoma patients [ 19 , 20 ]. The other cut points for the remaining three survival outcomes were higher.…”

“…No cross-reactivity was detected with other blood biomarkers such as CA125, CEA or PSA. No interference was detected with chemicals such as SN-38, 5-FU or triglycerides, cholesterol or hemoglobin [ 20 ]. hPG 80 values for 464 participants were successfully obtained, although 129 of them had values below the assay’s LoQ threshold.…”

“…Previous research has shown the clinical utility of hPG 80 to detect patients at risk for poor survival outcomes, even amongst those with early-stage disease [ 20 ]. So, its utility in a breast cancer cohort established to identify prognostic biomarkers was a unique opportunity to evaluate it in this patient group.…”

“…hPG 80 is directly associated with tumor cells survival [11,15,17,18]. More recently, in both renal and hepatocellular cancers, hPG 80 has shown a significant association with survival for both cancers [19,20]. The hepatocellular cancer patients showed a higher sensitivity to hPG 80 than alpha-fetoprotein (AFP) -the standard available diagnostic marker for hepatocellular cancer [20].…”

hPG80 (circulating progastrin) as a blood biomarker for high-grade glial tumors: A pilot study

“…In addition, a retrospective study of 143 patients with metastatic kidney cancer found that hPG 80 was detected in 94% of the patients ( 16 ). More recently, a retrospective study of 168 patients with hepatocellular carcinoma found that hPG 80 was detected in 84% of the patients ( 17 ).…”