Multi-dimensional omics characterization in glioblastoma identifies the purity-associated pattern and prognostic gene signatures

BACKGROUND: The presence of tumor-associated stroma and tumor-infiltrated immune cells have been largely reported across glioblastomas. Tumor purity, defined as the proportion of tumor cells in the tumor, was associated with the genomic and clinicopathologic features of the tumor and may alter the interpretation of glioblastoma biology. METHODS: We use an integrative approach to infer tumor purity based on multi-omic data and comprehensively evaluate the impact of tumor purity on glioblastoma (GBM) prognosis, genomic profiling, and the immune microenvironment in the Cancer Genome Atlas Consortium (TCGA) cohort. RESULTS: We found that low tumor purity was significantly associated with reduced survival time. Additionally, we established a purity-relevant 5-gene signature that was an independent prognostic biomarker and validated it in the TCGA, CGGA and GSE4412 cohort. Moreover, we correlated tumor purity with genomic characteristics and tumor microenvironment. We identified that gamma delta T cells in glioblastoma microenvironment were positively correlated with purity and served as a marker for favorable prognosis, which was validated in both TCGA and CGGA dataset. CONCLUSIONS: We observe the potential confounding effects of tumor purity on GBM clinical and molecular information interpretation. GBM microenvironment could be purity-dependent, which provides new insights into the clinical implications of glioblastoma.