# Project 1: Disparities in Mitochondrial Peptidomics and Transcriptomics in Prostate Cancer

> **NIH NIH U54** · FLORIDA AGRICULTURAL AND MECHANICAL UNIV · 2020 · $1,420

## Abstract

Mitochondrial dysfunction and mtDNA polymorphisms have been associated with prostate cancer (PC) biology.
We discovered a novel class of mitochondria-derived peptides (MDPs) that are transcribed from small open
reading frames within the mtDNA. These include humanin, SHLP-2, and MOTS-c, which are circulating
cytoprotective signaling peptides. Decreased MDP levels have been implicated in diseases of aging, and we
recently found that Blacks have lower circulating levels of humanin and SHLP2 than Whites. We hypothesize
that differences in MDP expression in minority men relative to Whites contribute to the elevated risk of PC. We
seek to test the potential of plasma MDPs and their prostate expression levels as biomarkers for PC risk, both
as pre-diagnostic biomarkers and as surrogate prognostic risk indicators in a group of men with and without PC
including White, Latino, and Black men. We recently reported that in a small cohort of Black and White men
undergoing prostate biopsy SHLP2 levels were significantly lower in men with PC vs. men without PC and that
Black men had significantly lower levels than White men. A SHLP2 level >350 pg/ml had a negative predictive
value of ≥95% for a negative biopsy regardless of race and may be an excellent biomarker to avoid biopsy. A
larger dataset is needed to validate our results, and this grant will dramatically expand this research question
and look at additional ethnic groups and their subpopulations. Our first goal for this project includes the analysis
of the association between serum SHLP2 levels and PC risk in ethnic minorities. We will leverage two ongoing
sample collection efforts at UF and USC to analyze 700 serum samples from White, Latino, and Black men (Aim
1). SHLP2 levels will be compared between men with and without PC and stratified by race. Our second goal is
to determine the association between additional plasma MDPs and PC risk among men of different ethnicities.
We will measure plasma levels of humanin, MOTS-c, SHLP2, and SHLP6 and determine the association
between these MDPs, race, and cancer status (Aim 2). Using whole transcriptome RNAseq analysis of RNA
from micro-dissected FFPE from prostate tumor patients who are Black, White, and Latino we will compare the
prostate mito-transcriptome for divergent expression of MDP transcripts and their relation to cancer severity and
ethnic origin (Aim 3). Finally, we will examine the contribution of mitochondrial DNA copy number in the
circulation and in benign and malignant prostate tissues, to PC risk and severity. Our study will be the first
comprehensive study of racial differences in mtDNAcn, mitochondrial-derived peptide expression and levels,
and their effect on PC. If successful, MDP levels may serve as diagnostic biomarkers of PC, particularly in
minority men. The expected finding, that MDP levels are regulated by interventions that may modify cancer risk
(such as diet and exercise, which raise MDP levels) could lead to a simple approach whe...

## Key facts

- **NIH application ID:** 10006099
- **Project number:** 5U54CA233396-03
- **Recipient organization:** FLORIDA AGRICULTURAL AND MECHANICAL UNIV
- **Principal Investigator:** Pinchas Cohen
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,420
- **Award type:** 5
- **Project period:** 2018-09-19 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006099

## Citation

> US National Institutes of Health, RePORTER application 10006099, Project 1: Disparities in Mitochondrial Peptidomics and Transcriptomics in Prostate Cancer (5U54CA233396-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10006099. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*