GDF15 expression in glioma is associated with malignant progression, immune microenvironment, and serves as a prognostic factor.

ABSTRACT

AIMS: Growth differentiation factor 15 (GDF15) is involved in lots of crucial inflammatory and immune response. The clinical and immune features for GDF15 in glioma have not been specifically investigated so far. METHODS: Gene expression profiles obtained from public glioma datasets were used to explore the biological function of GDF15 and its impact on immune microenvironment. Interference with GDF15 in several glioma cell lines to verify its functions in vitro. Survival data were used for the survival analysis and establishment of a nomogram predictive model. RESULTS: GDF15 was up-regulated in various malignant phenotypes of glioma. Function analysis and in vitro experiments revealed that GDF15 was associated with malignant progression and NF-κB pathway. GDF15 was closely correlated to inflammatory response, infiltrating immune cells, and immune checkpoint molecules, especially in lower grade glioma (LGG). High expression level of GDF15 predicted poor survival in LGG, while the effect on glioblastoma (GBM) was not significant. A nomogram predictive model combining GDF15 and other prognostic factors was constructed and showed ideal predictive performance. CONCLUSIONS: GDF15 could serve as an interesting prognostic biomarker for LGG. Regulating the expression of GDF15 may help solve the dilemma of immunotherapy in glioma.