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

Yi Xiong,Chang Li,Hang Cao,Siyi Wanggou,Xuejun Li,Zujian Xiong

doi:10.1186/s12935-020-1116-3

Yi Xiong, Chang Li + Show 4 more

Open Access

https://doi.org/10.1186/s12935-020-1116-3

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Abstract

BackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionsWe 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.

Highlights

The presence of tumor-associated stroma and tumor-infiltrated immune cells have been largely reported across glioblastomas
Tumor purity scores were calculated by consensus purity estimation (CPE) method based on ABSOLUTE, ESTIMATE, LUMP and IHC algorithms (Additional file 1: Table S1)
We observed that tumor purity inferred by the CPE method was significantly positively correlated with purity calculated based on ABSOLUTE, LUMP, ESTIMATE (Spearman’s correlation, rho = 0.90, 0.90, 0.76, respectively) (Fig. 1d), suggesting the rationality of this method

Summary

Introduction

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. Tumor purity is defined as the proportion of tumor cells in the tumor tissue. Xiong et al Cancer Cell Int (2020) 20:37 computational approaches were developed recently, and they were based on transcriptome data, DNA methylation data or genome data [8,9,10]. Purity estimates inferred by one certain omics data still confines the interpretation of purity in tumor biology systemically in previous studies [11, 12]. A recent study proposed a computational method for calculating the value of purity, namely, the consensus purity estimation (CPE), which was based on ABSOLUTE, ESTIMATE, LUMP and IHC methods [13]

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Results

Conclusion