An immunotherapy gene signature in several cancer types that is not detected by traditional differential expression analyses

The tumour microenvironment is the non-cancerous cells present in and around a tumour, including mainly immune cells, but also fibroblasts and cells that comprise supporting blood vessels. These non-cancerous components of the tumour may play an important role in cancer biology. They also have a strong influence on the genomic analysis of tumour samples, and may alter the biological interpretation of results.

Here researchers from UCSF present a systematic analysis using different measurement modalities of tumour purity in >10,000 samples across 21 cancer types from the Cancer Genome Atlas. Patients are stratified according to clinical features in an attempt to detect clinical differences driven by purity levels. They demonstrate the confounding effect of tumour purity on correlating and clustering tumours with transcriptomics data. Finally, using a differential expression method that accounts for tumour purity, the researchers find an immunotherapy gene signature in several cancer types that is not detected by traditional differential expression analyses.

rna-seq

Enriched pathways of differential expression adjusted for tumour purity. Pathway analysis of genes whose ranks advanced significantly in purity+ compared with purity−. The plot shows pathways that were enriched in at least one of the cancer types. Black: highly enriched; white: no enrichment. Analysis was performed using Ingenuity Pathway Analysis.

Aran D, Sirota M, Butte AJ. (2015) Systematic pan-cancer analysis of tumour purity. Nat Commun 6:8971. [article]

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