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

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...

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Published inScientific reports Vol. 7; no. 1; pp. 16862 - 14
Main Authors Lai, John, Moya, Leire, An, Jiyuan, Hoffman, Andrea, Srinivasan, Srilakshmi, Panchadsaram, Janaththani, Walpole, Carina, Perry-Keene, Joanna L., Chambers, Suzanne, Lehman, Melanie L., Nelson, Colleen C., Clements, Judith A., Batra, Jyotsna
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 04.12.2017
Nature Publishing Group
Nature Portfolio
Subjects
38/22
631/67/2322
631/67/68
Adult
Aged
Aged, 80 and over
Alleles
Androgens
Antigens, Neoplasm - genetics
Base Sequence
Case-Control Studies
Genetic analysis
Genotype
Health risk assessment
Humanities and Social Sciences
Humans
Kaplan-Meier Estimate
Male
Microsatellite Repeats - genetics
Middle Aged
multidisciplinary
Non-coding RNA
Nucleotide sequence
Odds Ratio
Prognosis
Proportional Hazards Models
Prostate cancer
Prostatic Neoplasms - genetics
Prostatic Neoplasms - mortality
Prostatic Neoplasms - pathology
Risk Factors
RNA, Long Noncoding - metabolism
Science
Science (multidisciplinary)
Short tandem repeats
Tumors
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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.
AbstractList 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.
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.
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.
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.
ArticleNumber 16862
Author Srinivasan, Srilakshmi
Panchadsaram, Janaththani
Chambers, Suzanne
Hoffman, Andrea
An, Jiyuan
Walpole, Carina
Lehman, Melanie L.
Clements, Judith A.
Perry-Keene, Joanna L.
Batra, Jyotsna
Moya, Leire
Nelson, Colleen C.
Lai, John
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SSID ssj0000529419
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Snippet Short tandem repeats (STRs) are repetitive sequences of a polymorphic stretch of two to six nucleotides. We hypothesized that STRs are associated with prostate...
Abstract Short tandem repeats (STRs) are repetitive sequences of a polymorphic stretch of two to six nucleotides. We hypothesized that STRs are associated with...
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SubjectTerms 38/22
631/67/2322
631/67/68
Adult
Aged
Aged, 80 and over
Alleles
Androgens
Antigens, Neoplasm - genetics
Base Sequence
Case-Control Studies
Genetic analysis
Genotype
Health risk assessment
Humanities and Social Sciences
Humans
Kaplan-Meier Estimate
Male
Microsatellite Repeats - genetics
Middle Aged
multidisciplinary
Non-coding RNA
Nucleotide sequence
Odds Ratio
Prognosis
Proportional Hazards Models
Prostate cancer
Prostatic Neoplasms - genetics
Prostatic Neoplasms - mortality
Prostatic Neoplasms - pathology
Risk Factors
RNA, Long Noncoding - metabolism
Science
Science (multidisciplinary)
Short tandem repeats
Tumors
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Title A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness
URI https://link.springer.com/article/10.1038/s41598-017-16700-y
https://www.ncbi.nlm.nih.gov/pubmed/29203868
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https://search.proquest.com/docview/1973021010
https://pubmed.ncbi.nlm.nih.gov/PMC5715103
https://doaj.org/article/5d9e5e6634f54987ae535d2c9dbf9217
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