Association Analysis of a Microsatellite Repeat in the TRIB1 Gene With Prostate Cancer Risk, Aggressiveness and Survival
With an estimated 1.1 million men worldwide diagnosed with prostate cancer yearly, effective and more specific biomarkers for early diagnosis could lead to better patient outcome. As such, novel genetic markers are sought for this purpose. The tribbles homologue 1 gene (TRIB1) has recently shown to...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2018.00428/full |
| _version_ | 1818966721222934528 |
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| author | Leire Moya Leire Moya John Lai John Lai Andrea Hoffman Andrea Hoffman Srilakshmi Srinivasan Srilakshmi Srinivasan Janaththani Panchadsaram Janaththani Panchadsaram Suzanne Chambers Suzanne Chambers Judith A. Clements Judith A. Clements Jyotsna Batra Jyotsna Batra Australian Prostate Cancer BioResource T. Yeadon P. Saunders A. Eckert J.A. Clements P. Heathcote G. Wood G. Malone H. Samaratunga A. Collins M. Turner K. Kerr |
| author_facet | Leire Moya Leire Moya John Lai John Lai Andrea Hoffman Andrea Hoffman Srilakshmi Srinivasan Srilakshmi Srinivasan Janaththani Panchadsaram Janaththani Panchadsaram Suzanne Chambers Suzanne Chambers Judith A. Clements Judith A. Clements Jyotsna Batra Jyotsna Batra Australian Prostate Cancer BioResource T. Yeadon P. Saunders A. Eckert J.A. Clements P. Heathcote G. Wood G. Malone H. Samaratunga A. Collins M. Turner K. Kerr |
| author_sort | Leire Moya |
| collection | DOAJ |
| description | With an estimated 1.1 million men worldwide diagnosed with prostate cancer yearly, effective and more specific biomarkers for early diagnosis could lead to better patient outcome. As such, novel genetic markers are sought for this purpose. The tribbles homologue 1 gene (TRIB1) has recently shown to have a role in prostate tumorigenesis and data-mining of prostate cancer expression data confirmed clinical significance of TRIB1 in prostate cancer. For the first time, a polymorphic microsatellite in this gene was studied for its potential association with prostate cancer risk and aggressiveness. Genomic DNA was extracted from a cohort of 1,152 prostate cancer patients and 1,196 cancer-free controls and the TTTTG-TRIB1 microsatellite was genotyped. The socio-demographic and clinical characteristics were analyzed using the non-parametric t-test and two-way ANOVA. Association of the TTTTG-TRIB1 microsatellite and prostate cancer risk and aggressiveness were analyzed by binary logistic regression and confirmed by bootstrapping. Total and prostate cancer mortality was analyzed using the Kaplan Meier test. Genotype and allele correlation with TRIB1 mRNA levels was analyzed using the non-parametric Kolmogorov–Smirnov test. To predict the effect that the TTTTG-TRIB1 polymorphisms had on the mRNA structure, the in silico RNA folding predictor tool, mfold, was used. By analyzing the publicly available data, we confirmed a significant over-expression of TRIB1 in prostate cancer compared to other cancer types, and an over-expression in prostate cancerous tissue compared to adjacent benign. Three alleles (three–five repeats) were observed for TTTTG-TRIB1. The three-repeat allele was associated with prostate cancer risk at the allele (OR = 1.16; P = 0.044) and genotypic levels (OR = 1.70; P = 0.006) and this association was age-independent. The four-repeat allele was inversely associated with prosatet cancer risk (OR = 0.57; P < 0.0001). TRIB1 expression was upregulated in tumors when compared to adjacent cancer-free tissue but was not allele specific. In silico analysis suggested that the TTTTG-TRIB1 alleles may alter TRIB1 mRNA structure. In summary, the three-repeat allele was significantly associated with prostate cancer risk, suggesting a biomarker potential for this microsatellite to predict prostate cancer. Further studies are needed to elucidate the functional role of this microsatellite in regulating TRIB1 expression, perhaps by affecting the TRIB1 mRNA structure and stability. |
| first_indexed | 2024-12-20T13:37:24Z |
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| language | English |
| last_indexed | 2024-12-20T13:37:24Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-a0db1f23459c45a49848bf14da270c352022-12-21T19:38:54ZengFrontiers Media S.A.Frontiers in Genetics1664-80212018-10-01910.3389/fgene.2018.00428353110Association Analysis of a Microsatellite Repeat in the TRIB1 Gene With Prostate Cancer Risk, Aggressiveness and SurvivalLeire Moya0Leire Moya1John Lai2John Lai3Andrea Hoffman4Andrea Hoffman5Srilakshmi Srinivasan6Srilakshmi Srinivasan7Janaththani Panchadsaram8Janaththani Panchadsaram9Suzanne Chambers10Suzanne Chambers11Judith A. Clements12Judith A. Clements13Jyotsna Batra14Jyotsna Batra15Australian Prostate Cancer BioResourceT. YeadonP. SaundersA. EckertJ.A. ClementsP. HeathcoteG. WoodG. MaloneH. SamaratungaA. CollinsM. TurnerK. KerrAustralian Prostate Cancer Research Centre – Queensland, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaCancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, AustraliaAustralian Prostate Cancer Research Centre – Queensland, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaCancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, AustraliaAustralian Prostate Cancer Research Centre – Queensland, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaCancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, AustraliaAustralian Prostate Cancer Research Centre – Queensland, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaCancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, AustraliaAustralian Prostate Cancer Research Centre – Queensland, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaCancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, AustraliaMenzies Health Institute Queensland, Griffith University, Gold Coast, QLD, AustraliaCancer Research Centre, Cancer Council Queensland, Brisbane, QLD, AustraliaAustralian Prostate Cancer Research Centre – Queensland, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaCancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, AustraliaAustralian Prostate Cancer Research Centre – Queensland, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaCancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, AustraliaWith an estimated 1.1 million men worldwide diagnosed with prostate cancer yearly, effective and more specific biomarkers for early diagnosis could lead to better patient outcome. As such, novel genetic markers are sought for this purpose. The tribbles homologue 1 gene (TRIB1) has recently shown to have a role in prostate tumorigenesis and data-mining of prostate cancer expression data confirmed clinical significance of TRIB1 in prostate cancer. For the first time, a polymorphic microsatellite in this gene was studied for its potential association with prostate cancer risk and aggressiveness. Genomic DNA was extracted from a cohort of 1,152 prostate cancer patients and 1,196 cancer-free controls and the TTTTG-TRIB1 microsatellite was genotyped. The socio-demographic and clinical characteristics were analyzed using the non-parametric t-test and two-way ANOVA. Association of the TTTTG-TRIB1 microsatellite and prostate cancer risk and aggressiveness were analyzed by binary logistic regression and confirmed by bootstrapping. Total and prostate cancer mortality was analyzed using the Kaplan Meier test. Genotype and allele correlation with TRIB1 mRNA levels was analyzed using the non-parametric Kolmogorov–Smirnov test. To predict the effect that the TTTTG-TRIB1 polymorphisms had on the mRNA structure, the in silico RNA folding predictor tool, mfold, was used. By analyzing the publicly available data, we confirmed a significant over-expression of TRIB1 in prostate cancer compared to other cancer types, and an over-expression in prostate cancerous tissue compared to adjacent benign. Three alleles (three–five repeats) were observed for TTTTG-TRIB1. The three-repeat allele was associated with prostate cancer risk at the allele (OR = 1.16; P = 0.044) and genotypic levels (OR = 1.70; P = 0.006) and this association was age-independent. The four-repeat allele was inversely associated with prosatet cancer risk (OR = 0.57; P < 0.0001). TRIB1 expression was upregulated in tumors when compared to adjacent cancer-free tissue but was not allele specific. In silico analysis suggested that the TTTTG-TRIB1 alleles may alter TRIB1 mRNA structure. In summary, the three-repeat allele was significantly associated with prostate cancer risk, suggesting a biomarker potential for this microsatellite to predict prostate cancer. Further studies are needed to elucidate the functional role of this microsatellite in regulating TRIB1 expression, perhaps by affecting the TRIB1 mRNA structure and stability.https://www.frontiersin.org/article/10.3389/fgene.2018.00428/fullshort tandem repeats (STRs)microsatellitetribbles homologue 1 gene (TRIB1)prostate cancerbiomarker |
| spellingShingle | Leire Moya Leire Moya John Lai John Lai Andrea Hoffman Andrea Hoffman Srilakshmi Srinivasan Srilakshmi Srinivasan Janaththani Panchadsaram Janaththani Panchadsaram Suzanne Chambers Suzanne Chambers Judith A. Clements Judith A. Clements Jyotsna Batra Jyotsna Batra Australian Prostate Cancer BioResource T. Yeadon P. Saunders A. Eckert J.A. Clements P. Heathcote G. Wood G. Malone H. Samaratunga A. Collins M. Turner K. Kerr Association Analysis of a Microsatellite Repeat in the TRIB1 Gene With Prostate Cancer Risk, Aggressiveness and Survival Frontiers in Genetics short tandem repeats (STRs) microsatellite tribbles homologue 1 gene (TRIB1) prostate cancer biomarker |
| title | Association Analysis of a Microsatellite Repeat in the TRIB1 Gene With Prostate Cancer Risk, Aggressiveness and Survival |
| title_full | Association Analysis of a Microsatellite Repeat in the TRIB1 Gene With Prostate Cancer Risk, Aggressiveness and Survival |
| title_fullStr | Association Analysis of a Microsatellite Repeat in the TRIB1 Gene With Prostate Cancer Risk, Aggressiveness and Survival |
| title_full_unstemmed | Association Analysis of a Microsatellite Repeat in the TRIB1 Gene With Prostate Cancer Risk, Aggressiveness and Survival |
| title_short | Association Analysis of a Microsatellite Repeat in the TRIB1 Gene With Prostate Cancer Risk, Aggressiveness and Survival |
| title_sort | association analysis of a microsatellite repeat in the trib1 gene with prostate cancer risk aggressiveness and survival |
| topic | short tandem repeats (STRs) microsatellite tribbles homologue 1 gene (TRIB1) prostate cancer biomarker |
| url | https://www.frontiersin.org/article/10.3389/fgene.2018.00428/full |
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