A global immune gene expression signature for human cancers

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.

We 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.

We 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.

Our 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.