Lipid Alterations in African American Men with Prostate Cancer

Anindita Ravindran; Danthasinghe Waduge Badrajee Piyarathna; Jie Gohlke; Vasanta Putluri; Tanu Soni; Stacy Lloyd; Patricia Castro; Subramaniam Pennathur; Jeffrey A Jones; Michael Ittmann; Nagireddy Putluri; George Michailidis; Thekkelnaycke M Rajendiran; Arun Sreekumar

doi:10.3390/metabo12010008

Lipid Alterations in African American Men with Prostate Cancer

Metabolites. 2021 Dec 22;12(1):8. doi: 10.3390/metabo12010008.

Authors

Anindita Ravindran^{1

2}, Danthasinghe Waduge Badrajee Piyarathna^{1

2}, Jie Gohlke^{1

2}, Vasanta Putluri³, Tanu Soni⁴, Stacy Lloyd^{1

5}, Patricia Castro^{6

7}, Subramaniam Pennathur^{8

9}, Jeffrey A Jones^{5

10

11}, Michael Ittmann^{5

6}, Nagireddy Putluri^{1

2

3

5}, George Michailidis¹², Thekkelnaycke M Rajendiran^{4

13

14}, Arun Sreekumar^{1

2

5}

Affiliations

¹ Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
² Center for Metabolism and Experimental Therapeutics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
³ Advanced Technology Core, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
⁴ Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, MI 48105, USA.
⁵ Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
⁶ Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
⁷ Human Tissue Acquisition & Pathology Shared Resource, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
⁸ Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI 48105, USA.
⁹ Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 84105, USA.
¹⁰ Department of Urology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
¹¹ Operative Care Line, Urology Section, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030, USA.
¹² Informatics Institute, University of Florida, Gainesville, FL 32611, USA.
¹³ Department of Pathology, University of Michigan, Ann Arbor, MI 48105, USA.
¹⁴ Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48105, USA.

Abstract

African-American (AA) men are more than twice as likely to die of prostate cancer (PCa) than European American (EA) men. Previous in silico analysis revealed enrichment of altered lipid metabolic pathways in pan-cancer AA tumors. Here, we performed global unbiased lipidomics profiling on 48 matched localized PCa and benign adjacent tissues (30 AA, 24 ancestry-verified, and 18 EA, 8 ancestry verified) and quantified 429 lipids belonging to 14 lipid classes. Significant alterations in long chain polyunsaturated lipids were observed between PCa and benign adjacent tissues, low and high Gleason tumors, as well as associated with early biochemical recurrence, both in the entire cohort, and within AA patients. Alterations in cholesteryl esters, and phosphatidyl inositol classes of lipids delineated AA and EA PCa, while the levels of lipids belonging to triglycerides, phosphatidyl glycerol, phosphatidyl choline, phosphatidic acid, and cholesteryl esters distinguished AA and EA PCa patients with biochemical recurrence. These first-in-field results implicate lipid alterations as biological factors for prostate cancer disparities.

Keywords: biochemical recurrence; cholesteryl esters; lipidomics; prostate cancer health disparity.

Abstract

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