4364 - Upregulation of sFRP3 circulating expression levels correlates survival outcomes in glioblastoma

Background

Glioblastoma (GBM) is characterized by invasion, heterogeneity and high angiogenesis, conferring a poor prognosis. The aim of our study was to assess serum proteins related to these hallmarks with potential prognostic value in GBM.

Methods

Serum samples from GBM patients (N = 57 pts) were collected before Stupp regimen. We defined as “LT survivors” (LTS) those pts above 36-months survival, and as “ST survivors” (STS) those below 6-months survival. In the discovery cohort (N = 25 pts), 4 pts were identified in each group. A pooled analysis from serum samples of each group was performed by a protein profiling platform based on antibody array technology. Expressed proteins were assessed for differential expression between the two groups. In silico validation by using data obtained from French glioma study at R2 was performed. In situ expression levels from selected proteins involved in tumor progression (TP), cell proliferation (CP), invasion (Inv) and cell death (CD) that significantly correlate (p < 0.05) with OS in gliomas were studied. ELISA analysis against an independent sample set from the validation cohort (n = 32 pts, LTS n = 4, STS n = 7) was used to verify expression levels of the target proteins.

Results

A total of 1000 proteins were analyzed by the array. 214 proteins showed differences in fluorescence intensity more than 10-fold between LTS vs STS. Among them, SMAD4, SMAD5, TWEAK, VEGFR2, WISP1, FGF21, NEUROD1, SFRP3, SFPR4 and Bax were selected since obtained the highest differences in fluorescence intensity and correlated with differential OS outcomes in silico. ELISA validation demonstrated SFRP3 to be upregulated in the STS group (media expression (pg/ml) STS=1849;LTS=1039) (p = 0.018). No statistically significant differences were observed in the expression levels for the other proteins between LTS and STS. In validation cohort, median overall survival according to SFRP3 expression (low/high) was 19.7 months (CI 95% 10.7-28.61) vs 9.42 months (CI 95% 3.11-15.72) respectively, although did not reach statistical significance (p = 0.073).

Conclusions

Higher circulating SFRP3 level has been associated with STS in GBM. Overexpression of serum SFPR3 in GBM may be a surrogate indicator of poorer prognosis. Further studies are warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

GEINO.

Disclosure

All authors have declared no conflicts of interest.