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- Title
ERR1 and PGC1α associated mitochondrial alterations correlate with pan-cancer disparity in African Americans.
- Authors
Badrajee Piyarathna, Danthasinghe Waduge; Balasubramanian, Akhila; Arnold, James M.; Lloyd, Stacy M.; Karanam, Balasubramanyam; Castro, Patricia; Ittmann, Michael M.; Putluri, Nagireddy; Navone, Nora; Jones, Jeffrey A.; Wendong Yu; Sandulache, Vlad C.; Sikora, Andrew G.; Michailidis, George; Sreekumar, Arun; Piyarathna, Danthasinghe Waduge Badrajee; Yu, Wendong
- Abstract
<bold>Background: </bold>African American (AA) patients have higher cancer mortality rates and shorter survival times compared to European American (EA) patients. Despite a significant focus on socioeconomic factors, recent findings strongly argue the existence of biological factors driving this disparity. Most of these factors have been described in a cancer-type specific context rather than a pan-cancer setting.<bold>Methods: </bold>A novel in silico approach based on Gene Set Enrichment Analysis (GSEA) coupled to Transcription Factor enrichment was carried out to identify common biological drivers of pan-cancer racial disparity using The Cancer Genome Atlas (TCGA) dataset. Mitochondrial content in patient tissues was examined using a multi-cancer tissue microarray approach (TMA).<bold>Results: </bold>Mitochondrial oxidative phosphorylation was uniquely enriched in AA tumors compared to EA tumors across various cancer types. AA tumors also showed strong enrichment for the ERR1-PGC1α-mediated transcriptional program, which has been implicated in mitochondrial biogenesis. TMA analysis revealed that AA cancers harbor significantly more mitochondria compared to their EA counterparts.<bold>Conclusions: </bold>These findings highlight changes in mitochondria as a common distinguishing feature between AA and EA tumors in a pan-cancer setting, and provide the rationale for the repurposing of mitochondrial inhibitors to treat AA cancers.
- Subjects
AFRICAN Americans; OXIDATIVE phosphorylation; CANCER-related mortality; SOCIOECONOMIC factors; TRANSCRIPTION factors
- Publication
Journal of Clinical Investigation, 2019, Vol 129, Issue 6, p2351
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI127579