# Aberrant Splice Variants as Potential Precision Biomarkers for Aggressive Prostate Cancers in African American Patients

> **NIH NIH SC1** · UNIVERSITY OF MARYLAND EASTERN SHORE · 2022 · $387,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Prostate cancer (PCa) is now the most frequently diagnosed cancer and the second most
common cause of cancer deaths in men in United States. Notably, African Americans (AAs)
exhibited 1.6-fold higher incidence and 2.4-fold higher mortality rates compared to European
Americans (EAs). Despite multiple socioeconomic factors postulated to explain the observed
PCa disparities, higher recurrence and mortality rates remained even after adjustment of
socioeconomic status in AAs, suggesting that intrinsic biological differences account for, at
least, part of PCa disparities.
Our previous genomic studies have revealed that intrinsic genomic differences do exist between
AA and EA PCa. These genetic elements, including population-specific and -enriched
microRNAs, mRNAs and alternative splicing variants, have been identified and were
hypothesized to contribute to the differential PCa properties between AA and EA. In the pilot
study, our preliminary results revealed ~2,500 differential splicing (DS) events occurring in AA
and EA PCa. Among these DS genes, >70% of the genes were functionally linked to cancer
diseases. These results lead to our hypothesis that aberrant mRNA splicing may play a critical
but largely unknown role for driving the PCa disparities.
Towards this hypothesis, we have performed RT-PCR validations and functional analyses of
AA-enriched splice variants (such as PIK3CD, FGFR3, TSC2 and RASGRP2 splice variants) in
PCa samples. Our preliminary results confirmed that these AA-enriched variants were highly
expressed in AA PCa and contributed to more aggressive cancer phenotypes. In this proposal,
we will focus on investigating the expression profiles of PIK3CD long and short splice variants
(PIK3CD-L and PIK3CD-S) in a panel of PCa and other solid/hematologic tumor cell lines, and
elucidating functional impacts of these splice variants in PCa aggressiveness and drug
resistance. Guided by strong preliminary data, we propose to pursue three Specific Aims to
character molecular functions of the PIK3CD splice variants underlying PCa aggressiveness: 1)
Validate the expression profiles of PIK3CD splice variants in PCa specimens and cell lines
derived from AA and EA patients; 2) Determine the functional roles of PIK3CD-S expression in
disease aggressiveness and drug resistance in PCa and evaluate the feasibility of PIK3CD-
S/PIK3CD-L ratios as potential biomarker; and 3) Screen for the effective therapeutic molecules
(small molecule inhibitors, siRNAs and/or splice switching oligos) to reduce the cancer
phenotypes in PIK3CD-S overexpressing cells.
Collectively, our proposed research will broadly contribute to the field of cancer health
disparities by characterizing the molecular signatures of aberrant splice variants in cancers
(including PCa and other solid/hematologic tumors), and deciphering the molecular mechanisms
of aberrant splicing underlying PCa aggressiveness (i.e. enhanced cell proliferation and
invasion) and drug re...

## Key facts

- **NIH application ID:** 10466902
- **Project number:** 5SC1GM127256-04
- **Recipient organization:** UNIVERSITY OF MARYLAND EASTERN SHORE
- **Principal Investigator:** Bi-Dar Wang
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $387,500
- **Award type:** 5
- **Project period:** 2019-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10466902

## Citation

> US National Institutes of Health, RePORTER application 10466902, Aberrant Splice Variants as Potential Precision Biomarkers for Aggressive Prostate Cancers in African American Patients (5SC1GM127256-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10466902. Licensed CC0.

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