A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness.

Lai, J; Moya, L; An, J; Hoffman, A; Srinivasan, S; Panchadsaram, J; Walpole, C; Perry-Keene, JL; Chambers, S; Australian Prostate Cancer BioResource,; Lehman, ML; Nelson, CC; Clements, JA; Batra, J

A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness.

Lai, J Moya, L An, J Hoffman, A Srinivasan, S Panchadsaram, J Walpole, C Perry-Keene, JL Chambers, S

Australian Prostate Cancer BioResource, Lehman, ML Nelson, CC Clements, JA Batra, J

Permalink

Publisher:: NATURE PUBLISHING GROUP
Publication Type:: Journal Article
Citation:: Sci Rep, 2017, 7, (1), pp. 16862
Issue Date:: 2017-12-04

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Adobe PDF

Download Published versionAdobe PDF (2.26 MB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Lai, J
dc.contributor.author	Moya, L
dc.contributor.author	An, J
dc.contributor.author	Hoffman, A
dc.contributor.author	Srinivasan, S
dc.contributor.author	Panchadsaram, J
dc.contributor.author	Walpole, C
dc.contributor.author	Perry-Keene, JL
dc.contributor.author	Chambers, S https://orcid.org/0000-0003-2369-6111
dc.contributor.author	Australian Prostate Cancer BioResource,
dc.contributor.author	Lehman, ML
dc.contributor.author	Nelson, CC
dc.contributor.author	Clements, JA
dc.contributor.author	Batra, J
dc.date.accessioned	2022-04-19T02:04:16Z
dc.date.available	2017-11-10
dc.date.available	2022-04-19T02:04:16Z
dc.date.issued	2017-12-04
dc.identifier.citation	Sci Rep, 2017, 7, (1), pp. 16862
dc.identifier.issn	2045-2322
dc.identifier.issn	2045-2322
dc.identifier.uri	http://hdl.handle.net/10453/156403
dc.description.abstract	Short tandem repeats (STRs) are repetitive sequences of a polymorphic stretch of two to six nucleotides. We hypothesized that STRs are associated with prostate cancer development and/or progression. We undertook RNA sequencing analysis of prostate tumors and adjacent non-malignant cells to identify polymorphic STRs that are readily expressed in these cells. Most of the expressed STRs in the clinical samples mapped to intronic and intergenic DNA. Our analysis indicated that three of these STRs (TAAA-ACTG2, TTTTG-TRIB1, and TG-PCA3) are polymorphic and differentially expressed in prostate tumors compared to adjacent non-malignant cells. TG-PCA3 STR expression was repressed by the anti-androgen drug enzalutamide in prostate cancer cells. Genetic analysis of prostate cancer patients and healthy controls (N > 2,000) showed a significant association of the most common 11 repeat allele of TG-PCA3 STR with prostate cancer risk (OR = 1.49; 95% CI 1.11-1.99; P = 0.008). A significant association was also observed with aggressive disease (OR = 2.00; 95% CI 1.06-3.76; P = 0.031) and high mortality rates (HR = 3.0; 95% CI 1.03-8.77; P = 0.045). We propose that TG-PCA3 STR has both diagnostic and prognostic potential for prostate cancer. We provided a proof of concept to be applied to other RNA sequencing datasets to identify disease-associated STRs for future clinical exploratory studies.
dc.format	Electronic
dc.language	eng
dc.publisher	NATURE PUBLISHING GROUP
dc.relation.ispartof	Sci Rep
dc.relation.isbasedon	10.1038/s41598-017-16700-y
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Alleles
dc.subject.mesh	Antigens, Neoplasm
dc.subject.mesh	Base Sequence
dc.subject.mesh	Case-Control Studies
dc.subject.mesh	Genotype
dc.subject.mesh	Humans
dc.subject.mesh	Kaplan-Meier Estimate
dc.subject.mesh	Male
dc.subject.mesh	Microsatellite Repeats
dc.subject.mesh	Middle Aged
dc.subject.mesh	Odds Ratio
dc.subject.mesh	Prognosis
dc.subject.mesh	Proportional Hazards Models
dc.subject.mesh	Prostatic Neoplasms
dc.subject.mesh	RNA, Long Noncoding
dc.subject.mesh	Risk Factors
dc.subject.mesh	Humans
dc.subject.mesh	Prostatic Neoplasms
dc.subject.mesh	Antigens, Neoplasm
dc.subject.mesh	Prognosis
dc.subject.mesh	Proportional Hazards Models
dc.subject.mesh	Odds Ratio
dc.subject.mesh	Risk Factors
dc.subject.mesh	Case-Control Studies
dc.subject.mesh	Base Sequence
dc.subject.mesh	Microsatellite Repeats
dc.subject.mesh	Genotype
dc.subject.mesh	Alleles
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Middle Aged
dc.subject.mesh	Male
dc.subject.mesh	Kaplan-Meier Estimate
dc.subject.mesh	RNA, Long Noncoding
dc.title	A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness.
dc.type	Journal Article
utslib.citation.volume	7
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
utslib.copyright.status	open_access	*
dc.date.updated	2022-04-19T02:04:14Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	7
utslib.citation.issue	1

Abstract:

Short tandem repeats (STRs) are repetitive sequences of a polymorphic stretch of two to six nucleotides. We hypothesized that STRs are associated with prostate cancer development and/or progression. We undertook RNA sequencing analysis of prostate tumors and adjacent non-malignant cells to identify polymorphic STRs that are readily expressed in these cells. Most of the expressed STRs in the clinical samples mapped to intronic and intergenic DNA. Our analysis indicated that three of these STRs (TAAA-ACTG2, TTTTG-TRIB1, and TG-PCA3) are polymorphic and differentially expressed in prostate tumors compared to adjacent non-malignant cells. TG-PCA3 STR expression was repressed by the anti-androgen drug enzalutamide in prostate cancer cells. Genetic analysis of prostate cancer patients and healthy controls (N > 2,000) showed a significant association of the most common 11 repeat allele of TG-PCA3 STR with prostate cancer risk (OR = 1.49; 95% CI 1.11-1.99; P = 0.008). A significant association was also observed with aggressive disease (OR = 2.00; 95% CI 1.06-3.76; P = 0.031) and high mortality rates (HR = 3.0; 95% CI 1.03-8.77; P = 0.045). We propose that TG-PCA3 STR has both diagnostic and prognostic potential for prostate cancer. We provided a proof of concept to be applied to other RNA sequencing datasets to identify disease-associated STRs for future clinical exploratory studies.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/156403