Lipid Alterations in African American Men with Prostate Cancer.

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

doi:10.3390/metabo12010008

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.

Highlights

Prostate cancer (PCa) progression is twice as aggressive and more than twice as morbid in African American (AA) men compared to European American (EA) men, yet the specific biochemical basis underlying this disparity remains unknown [1]
Patients (Figure 1C, FDR < 0.1), prominent elevations were seen in the levels of individual lipids belonging to Cholesteryl Ester (CE) and TG
The levels of individual lipids belonging to SM, Phosphatidyl Serine (PS), P-Phosphatidyl Ethanolamine (PE), Phosphatidyl Inositol (PI), and Phosphatidyl Glycerol (PG) were reduced in both comparisons

Summary

Introduction

Prostate cancer (PCa) progression is twice as aggressive and more than twice as morbid in African American (AA) men compared to European American (EA) men, yet the specific biochemical basis underlying this disparity remains unknown [1]. While environmental and socioeconomic factors such as diet and access to proper healthcare may be significant causes for increased mortality rates associated with PCa in AA men, recent reports suggest that metabolic alterations may drive the disparity in PCa progression [2]. Elevated levels of triglycerides in plasma have been associated with PCa risk and poor clinical outcome in AA men [5]. Elevated cholesterol levels in serum have been reported to be associated with increased biochemical recurrence (BCR), in AA men with PCa [5]. The global changes in the lipidome in AA and EA PCa tissues have not been examined

Methods

Results

Conclusion