A global immune gene expression signature for human cancers.

Yuexin Liu

doi:10.18632/oncotarget.26773

Abstract

BackgroundExcept for a few, the immune gene signatures for most cancer types are not available. We sought to identify a global immune gene signature that is applicable to all human cancers.ResultsWe identified an immune gene signature that was intimately correlated with tumor immune characteristics of human cancers and consisted of 382 genes indicative of different immune cell types. The T helper type 1 and 2 cell activation pathway was most significantly enriched in this global immune gene set, while transcription factors, such as SPI1 and STAT family members, were the top regulators of this gene signature. Skin cutaneous melanoma with higher expression of this immune gene signature had significantly longer survival than those with lower immune gene expression. Breast cancer patients with higher immune gene signature were significantly associated with advanced-stage.MethodsWe analyzed the gene expression profiles of 10,062 tumor samples from 32 cancer types in The Cancer Genome Atlas Pan-Cancer data set. Hierarchical clustering analysis of previously-defined immune genes was performed to identify a pan-cancer immune gene signature. Pathway and upstream regulator analyses were used to identify significantly enriched signaling pathways and transcription factors. Kaplan-Meier analysis was used to evaluate the survival difference between dichotomic groups with different immune gene signatures. Correlation of immune gene signature with tumor stage was also examined.ConclusionsOur identified immune gene signature is applicable in human cancers and can be used to characterize tumor immunogenicity within and across cancer types. Clinical implication of this immune gene set warrants future investigation.

Highlights

Immunotherapy is emerging as a promising cancer treatment and has revolutionized the mechanistic understanding of tumorigenesis
Our identified immune gene signature is applicable in human cancers and can be used to characterize tumor immunogenicity within and across cancer types
Identification of a global immune gene expression signature in human cancer To identify a global immune gene signature, we have employed an unbiased approach in this study and carried out an unsupervised hierarchical clustering analysis of 10,062 human cancer samples and 1,031 reliably measured immune genes (Figure 1)

Summary

Introduction

Immunotherapy is emerging as a promising cancer treatment and has revolutionized the mechanistic understanding of tumorigenesis. The response rate varies in patients both within and across cancer types. Bioinformatics analysis of high-throughput gene expression profiling has enabled identification of clinically-relevant molecular subtypes and has enhanced our understanding of molecular abnormalities of cancer [3,4,5,6]. Immune gene expression signatures have been identified to characterize tumor immunity and predict the response to immunotherapy [1, 7, 8]. The Cancer Genome Atlas (TCGA) PanCanAtlas research group used immune gene sets to determine immune-related molecular subtypes [10]. Except for a few, the immune gene signatures for most cancer types are not available. We sought to identify a global immune gene signature that is applicable to all human cancers

Methods

Results

Conclusion