gms | German Medical Science

Objective: ALDH1A3 is an enzyme and a member of the aldehyde dehydrogenases (ALDHs) superfamily. Recently it emerges as cancer stem-cell marker in neoplasms including glioblastoma (GBM). However, the comprehensive information of ALDH1A3 in human GBM is still not fully known. The present study attempted to investigate the expression manner of ALDH1A3 in human GBM tissues and its association with clinical parameters.

Methods: Thirty tissue samples of primary GBM and 9 controls were enrolled in this study. The level of ALDH1A3 mRNA and protein was detected by real-time RT-PCR and Western blot, respectively. The regional and cellular expression of ALDH1A3 was evaluated respectively by immunohistochemistry (IHC) and by double immunofluorescence (IF) staining. The association of ALDH1A3 expression with multiple clinical parameters was analyzed.

Results: The mRNA level ofALDH1A3 was significantly lower in GBM compared with the controls (p<0.05), which is in accordance with the result from the TCGA database. Interestingly, subgroup analysis showed 2.5-fold higher ALDH1A3 mRNA in GBMs with infiltration of the subventricular zone (SVZ) than that without SVZ-involvement. IHC classified two groups of GBM expressing low/negative and high ALDH1A3, which was confirmed by Western blot. The higher expression of ALDH1A3 was accompanied by an activation of Akt but reversely associated with PTEN expression. The immunoreactivity of ALDH1A3 was detected mostly in the infiltrative area and occasionally in the tumor center. Double IF staining indicated the co-expression of ALDH1A3 with GFAP in glia-shaped cells as well as in some tumor cells; but the immunoreactivity of ALDH1A3 does not overlap with vWF, CD68, CD133, and PCNA. Further analysis demonstrated a positive association of ALDH1A3 protein expression with the tumor edema grade (p = 0.0193) and with overall survival of patients (p = 0.009).

Conclusion: The protein expression of ALDH1A3 is associated with the overall survival of GBM, suggesting ALDH1A3 as a possible predictive marker and a potential therapeutic target for GBM. In this regard, a personalized strategy should be considered due to the heterogeneous manner of ALDH1A3 expression in asubgroup of GBM patients.