Prognostic Significance and Functional Mechanism of UTS2 in Glioblastoma Multiforme

Aim: We aimed to explore the role of urotensin 2 (UTS2) in glioblastoma (GBM).

Background: GBM is the most malignant primary brain cancer with a poor prognosis. Previous studies have suggested that GBM vessels undergo dynamic remodeling modulated by tumor vasodilation and vasoconstriction instead of tumor angiogenesis.

Objective: Here, we have first investigated the expression and function of UTS2, a potent vasoconstrictor, in GBM.

Methods: The mRNA expression profiles and clinical information of GBM patients were obtained from the TCGA database. The clinical relevance of UTS2 was explored by the Mann-Whitney U test and Cox hazard regression survival test. We further explored the role of UTS2 in GBM cell proliferation, migration, and tumor immune microenvironment. Moreover, we established the in vivo mice model to validate its oncogenic effects on GBM progression.

Results: Although we did not find significant correlations between UTS2 expression and patients’ clinical characteristics, UTS2 was identified as a valid independent prognostic indicator according to multivariate survival analysis. Knockdown of UTS2 resulted in decreased GBM cell proliferation and migration. In addition, functional enrichment analysis implied UTS2 to be involved in the regulation of the immune microenvironment. In vivo studies showed that UTS2 knockdown suppressed GBM xenograft growth, highlighting the tumor-promoting effects of UTS2 on GBM.

Conclusion: Our study identified that UTS2 could predict the prognosis of GBM patients and provided evidence regarding its oncogenic effects both in vitro and in vivo.