Association between post-operative hPG₈₀ (circulating progastrin) detectable level and worse prognosis in glioblastoma

Background: Patients with glioblastomas have a dismal prognosis, and there is no circulating predictive or prognostic biomarker. Circulating progastrin, hPG₈₀, is a tumor-promoting peptide present in the blood of patients with various cancers that has been shown to have prognostic value. We evaluated the prognostic value of plasma hPG₈₀ in patients with isocitrate dehydrogenase-wild type glioblastoma after surgery.

Patients and methods: A multicentric retrospective study in glioblastoma patients treated with standard radio-chemotherapy was conducted. The hPG₈₀ levels were measured in plasma EDTA samples collected after surgery with an ELISA DxPG80.lab kit (Biodena Care, Montpellier, France), which has a detection threshold of 1.2 pM. The relationship between post-operative hPG₈₀ plasma levels, in combination with other known prognostic factors, and patients' progression-free survival (PFS) and overall survival (OS) was evaluated.

Results: Sixty-nine patients were assessable. Plasma samples were collected after tumor biopsy (B), partial resection (PR), and complete resection (CR) for 22, 25, and 22 patients, respectively. At a median concentration of 5.37 pM (interquartile range 0.00-13.90 pM), hPG₈₀ was detected in 48 (70%) patients (hPG₈₀+). CR was associated with significant lower values of hPG₈₀ levels: the median value was 0.7 versus 9.1 pM for PR (P = 0.02) and 8.3 pM for B (P = 0.004). The hPG₈₀ detection rate was also significantly lower: 50% (CR) versus 72% (PR) versus 86% (B) (P = 0.005). The median follow-up was 39 months [22.4 months-not reached]. hPG₈₀ post-operative detection was associated with numerically shorter PFS (6.4 versus 9.4 months, P = 0.13) and OS (14.5 versus 20.9 months, P = 0.11). In multivariate analysis, hPG₈₀ was a prognostic factor for OS (P = 0.034).

Conclusions: Circulating hPG₈₀ could serve as a new prognostic biomarker after surgery in patients with glioblastoma treated with radio-chemotherapy.