Pan-cancer analyses of human nuclear receptors reveal transcriptome diversity and prognostic value across cancer types

The human nuclear receptor (NR) superfamily comprises 48 ligand-dependent transcription factors that play regulatory roles in physiology and pathophysiology. In cancer, NRs have long served as predictors of disease stratification, treatment response, and clinical outcome. The Cancer Genome Atlas (TCGA) Pan-Cancer project provides a wealth of genetic data for a large number of human cancer types. Here, we examined NR transcriptional activity in 8,526 patient samples from 33 TCGA 'Pan-Cancer' diseases and 11 'Pan-Cancer' organ systems using RNA sequencing data. The web-based Kaplan-Meier (KM) plotter tool was then used to evaluate the prognostic potential of NR gene expression in 21/33 cancer types. Although, most NRs were significantly underexpressed in cancer, NR expression (moderate to high expression levels) was predominantly restricted (46%) to specific tissues, particularly cancers representing gynecologic, urologic, and gastrointestinal 'Pan-Cancer' organ systems. Intriguingly, a relationship emerged between recurrent positive pairwise correlation of Class IV NRs in most cancers. NR expression was also revealed to play a profound effect on patient overall survival rates, with ≥5 prognostic NRs identified per cancer type. Taken together, these findings highlighted the complexity of NR transcriptional networks in cancer and identified novel therapeutic targets for specific cancer types.