Patient-derived primary culture-based prognostic model to predict tumor recurrence in patients with glioma

Abstract

Background

The prognosis for glioma patients remains grim despite aggressive treatment approaches. Current molecular profiles have limitations in predicting glioma recurrence, highlighting the need for new and improved prognostic biomarkers. We investigated whether the growth kinetics of patient-derived glioma cultures (PDGCs) can offer valuable prognostic insights to predict tumor recurrence. Additionally, we examined the expression of glial-mesenchymal transition (GMT) markers in PDGCs to assess their potential as additional prognostic biomarkers.

Methods

130 patients diagnosed with primary glioma via MRI scans were prospectively enrolled. Surgical tumor tissues were collected from all participants and used to establish patient-derived glioma cultures (PDGCs). The growth kinetics and colony-forming ability of the respective PDGCs were calculated to derive proliferation index (PI) for each patient. Progression-free survival (PFS) and overall survival (OS) served as the primary outcome measures.

Results

We established short-term glioma cultures in 98 clinical samples, regardless of the CNS WHO tumor grade, IDH1/2 mutation and 19/19q codeletion status and maintained active cell proliferation for at least 10–12 passages. However, we observed two distinct growth kinetic patterns among PDGCs. Based on their proliferation index (PI), we categorized patients into either high proliferation index (HPI) or low proliferation index (LPI) group. Furthermore, we noted a differential expression profile of GMT markers between HPI and LPI patients. The proliferation index (PI) exhibited a significant correlation with progression-free survival (PFS), while the expression of GMT marker vimentin was associated with overall survival (OS).

Conclusion

The PDGC-derived Proliferation Index (PI) can serve as a predictive tool for tumor recurrence, independent of clinical or tumor-related factors. Moreover, reduced vimentin expression is a positive indicator for glioma patients' overall survival status.