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ERR1 and PGC1α associated mitochondrial alterations correlate with pan-cancer disparity in African Americans.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2019 Mar 28; Vol. 129 (6), pp. 2351-2356. Date of Electronic Publication: 2019 Mar 28. - Publication Year :
- 2019
-
Abstract
- Background: 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.<br />Methods: 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).<br />Results: 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.<br />Conclusions: 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 :
- Female
Humans
Male
Mitochondria metabolism
Mitochondria pathology
Neoplasm Proteins metabolism
Neoplasms metabolism
Neoplasms pathology
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism
Receptors, Estrogen metabolism
Transcription, Genetic
White People genetics
ERRalpha Estrogen-Related Receptor
Black or African American genetics
Databases, Nucleic Acid
Mitochondria genetics
Neoplasm Proteins genetics
Neoplasms genetics
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha genetics
Receptors, Estrogen genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 129
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 30920960
- Full Text :
- https://doi.org/10.1172/JCI127579