Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
ERR1- and PGC1α-associated mitochondrial alterations correlate with pan-cancer disparity in African Americans
Danthasinghe Waduge Badrajee Piyarathna, … , George Michailidis, Arun Sreekumar
Danthasinghe Waduge Badrajee Piyarathna, … , George Michailidis, Arun Sreekumar
Published March 28, 2019
Citation Information: J Clin Invest. 2019;129(6):2351-2356. https://doi.org/10.1172/JCI127579.
View: Text | PDF
Clinical Medicine Metabolism Oncology

ERR1- and PGC1α-associated mitochondrial alterations correlate with pan-cancer disparity in African Americans

  • Text
  • PDF
Abstract

BACKGROUND African American patients have higher cancer mortality rates and shorter survival times compared with European American 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.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 data set. Mitochondrial content in patient tissues was examined using a multi-cancer tissue microarray approach (TMA).RESULTS Mitochondrial oxidative phosphorylation was uniquely enriched in tumors from African American patients compared with tumors of various cancer types from European American patients. Tumors from African American patients also showed strong enrichment for the ERR1-PGC1α–mediated transcriptional program, which has been implicated in mitochondrial biogenesis. TMA analysis revealed that cancers from African American patients harbor significantly more mitochondria compared with the same cancers from European American patients.CONCLUSION These findings highlight changes in mitochondria as a common distinguishing feature among tumors from African American versus European American patients in a pan-cancer setting, and provide the rationale for the repurposing of mitochondrial inhibitors to treat cancers from African American patients.FUNDING This research was partially supported by National Institutes of Health grants NIH U01 CA167234, NIH 1 U01 CA179674-01A1, 5R01GM11402903, 1U01CA23548701, U01 CA167234, R01CA220297, and R01CA216426; pilot and shared resources support from Dan L. Duncan Cancer Center grant P30 CA125123; and NCI SPORE pilot grant NIH P50 CA186784. It was also partially supported by the Diana Helis Henry Medical Research Foundation; the Brockman Foundation; Agilent Technologies; Department of Defense grants W81XWH-12-1-0130 and W81XWH-12-1-0046; Cancer Prevention Research Institute of Texas grant RP120092; a Prostate Cancer Foundation Challenge Award; National Science Foundation grant DMS-1545277; and American Cancer Society grant 127430-RSG-15-105-01-CNE.

Authors

Danthasinghe Waduge Badrajee Piyarathna, Akhila Balasubramanian, James M. Arnold, Stacy M. Lloyd, Balasubramanyam Karanam, Patricia Castro, Michael M. Ittmann, Nagireddy Putluri, Nora Navone, Jeffrey A. Jones, Wendong Yu, Vlad C. Sandulache, Andrew G. Sikora, George Michailidis, Arun Sreekumar

×

Full Text PDF | Download (3.08 MB)

Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts