Race-related Alternative Splicing: Novel Targets in Prostate Cancer (PCaP splicing)

Data from evaluating prostate cancer (PCa) biopsy tissue from AA and white patients has led to the discovery of alternative splicing as a novel molecular mechanism underlying more aggressive PCa in AA men. Coded archival radical prostatectomy tissue specimens and annotated clinical data, questionnaire data, and ancestral genotyping data will be obtained from the racially diverse and federally funded North Carolina-Louisiana PCa Project (NC-LA PCaP). We will use 33 tissue specimens from each of the following 6 groups (n=198 total): white low aggressive, white intermediate aggressive, white high aggressive, AA low aggressive, AA intermediate aggressive and AA high aggressive. The aforementioned tissues will first be screened for tumor content and Gleason grade by a genitourinary pathologist. To identify race-related splice variants, RNA will be isolated for targeted sequencing of prioritized race-related alternatively spliced genes using the NimbleGen SeqCap Target Enrichment, SeqCap RNA System to capture regions of interest and the Illumina HiSeq sequencing platform to sequence these regions at a depth and coverage sufficient to accurately call alternative splicing events.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Other: No interventions - retrospective data collection

• Study Type: Observational
• Enrollment (Actual): 169

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

The study population includes AA and white male patients having confirmed prostate cancer and enrolled in NC-LA PCaP, a population-based, case-only study of prostate cancer in AA and white men in NC and LA. Radical prostatectomy specimens will be selected from AA and white patients who have consented to NC-LA PCaP and have adequate tumor specimens of appropriate aggressiveness banked.

Description

Inclusion Criteria:

1. Confirmed diagnosis of prostate cancer.
2. Self-reported race of AA or white.
3. Availability of five unstained slides per radical prostatectomy specimen and an associated Hematoxylin and Eosin stained slide for each radical prostatectomy specimen from NC-LA PCaP.
4. Classification of prostate cancer of low, intermediate or high aggressiveness, as defined by NC-LA PCaP.

Exclusion Criteria:

1. Obtained radical prostatectomy tissue is inadequate for RNA analysis and/or is not positive for adenocarcinoma of the prostate of low, intermediate or high aggressiveness.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
white low aggressive; low aggressive = Gleason score < 7 and stage cT1-cT2 and PSA < 10 ng/ml	Other: No interventions - retrospective data collection; No new patients will be consented to this study. Only retrospective data will be collected on prostatectomy specimens and correlated with health data
white high aggressive; high aggressive = Gleason score ≥ 8 or PSA > 20 ng/ml or Gleason score = 7 and stage cT3-cT4	Other: No interventions - retrospective data collection; No new patients will be consented to this study. Only retrospective data will be collected on prostatectomy specimens and correlated with health data
white intermediate aggressive; intermediate aggressive = all other cases	Other: No interventions - retrospective data collection; No new patients will be consented to this study. Only retrospective data will be collected on prostatectomy specimens and correlated with health data
AA low aggressive; low aggressive = Gleason score < 7 and stage cT1-cT2 and PSA < 10 ng/ml	Other: No interventions - retrospective data collection; No new patients will be consented to this study. Only retrospective data will be collected on prostatectomy specimens and correlated with health data
AA high aggressive; high aggressive = Gleason score ≥ 8 or PSA > 20 ng/ml or Gleason score = 7 and stage cT3-cT4	Other: No interventions - retrospective data collection; No new patients will be consented to this study. Only retrospective data will be collected on prostatectomy specimens and correlated with health data
AA intermediate aggressive; intermediate aggressive = all other cases	Other: No interventions - retrospective data collection; No new patients will be consented to this study. Only retrospective data will be collected on prostatectomy specimens and correlated with health data

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of candidate race-related splice variants in localized prostate cancer of varying degrees of aggressiveness	at the time of analysis

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Steve Patierno, PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2018
• Primary Completion (Actual): July 14, 2021
• Study Completion (Actual): July 14, 2021

Study Registration Dates

• First Submitted: January 31, 2018
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Actual): February 2, 2022
• Last Update Submitted That Met QC Criteria: February 1, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: Pro00091092

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No