Serrate RNA Effector Molecule (SRRT) Is Associated with Prostate Cancer Progression and Is a Predictor of Poor Prognosis in Lethal Prostate Cancer
Arsenite-resistance protein 2, also known as serrate RNA effector molecule (ARS2/SRRT), is known to be involved in cellular proliferation and tumorigenicity. However, its role in prostate cancer (PCa) has not yet been established. We investigated the potential role of SRRT in 496 prostate samples in...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/10/2867 |
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| author | Yaser Gamallat Muhammad Choudhry Qiaowang Li Jon George Rokne Reda Alhajj Ramy Abdelsalam Sunita Ghosh Jaron Arbet Paul C. Boutros Tarek A. Bismar |
| author_facet | Yaser Gamallat Muhammad Choudhry Qiaowang Li Jon George Rokne Reda Alhajj Ramy Abdelsalam Sunita Ghosh Jaron Arbet Paul C. Boutros Tarek A. Bismar |
| author_sort | Yaser Gamallat |
| collection | DOAJ |
| description | Arsenite-resistance protein 2, also known as serrate RNA effector molecule (ARS2/SRRT), is known to be involved in cellular proliferation and tumorigenicity. However, its role in prostate cancer (PCa) has not yet been established. We investigated the potential role of SRRT in 496 prostate samples including benign, incidental, advanced, and castrate-resistant patients treated by androgen deprivation therapy (ADT). We also explored the association of SRRT with common genetic aberrations in lethal PCa using immunohistochemistry (IHC) and performed a detailed analysis of SRRT expression using The Cancer Genome Atlas (TCGA PRAD) by utilizing RNA-seq, clinical information (pathological T category and pathological Gleason score). Our findings indicated that high SRRT expression was significantly associated with poor overall survival (OS) and cause-specific survival (CSS). SRRT expression was also significantly associated with common genomic aberrations in lethal PCa such as PTEN loss, ERG gain, mutant TP53, or ATM. Furthermore, TCGA PRAD data revealed that high SRRT mRNA expression was significantly associated with higher Gleason scores, PSA levels, and T pathological categories. Gene set enrichment analysis (GSEA) of RNAseq data from the TCGA PRAD cohort indicated that <i>SRRT</i> may play a potential role in regulating the expression of genes involved in prostate cancer aggressiveness. Conclusion: The current data identify the SRRT’s potential role as a prognostic for lethal PCa, and further research is required to investigate its potential as a therapeutic target. |
| first_indexed | 2024-03-11T03:52:10Z |
| format | Article |
| id | doaj.art-db71055fb1f44d458345f2b52f9cbb20 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T03:52:10Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-db71055fb1f44d458345f2b52f9cbb202023-11-18T00:50:06ZengMDPI AGCancers2072-66942023-05-011510286710.3390/cancers15102867Serrate RNA Effector Molecule (SRRT) Is Associated with Prostate Cancer Progression and Is a Predictor of Poor Prognosis in Lethal Prostate CancerYaser Gamallat0Muhammad Choudhry1Qiaowang Li2Jon George Rokne3Reda Alhajj4Ramy Abdelsalam5Sunita Ghosh6Jaron Arbet7Paul C. Boutros8Tarek A. Bismar9Department of Pathology and Laboratory Medicine, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, CanadaDepartment of Pathology and Laboratory Medicine, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, CanadaDepartment of Computer Science, University of Calgary, Calgary, AB T2N 1N4, CanadaDepartment of Computer Science, University of Calgary, Calgary, AB T2N 1N4, CanadaDepartment of Computer Science, University of Calgary, Calgary, AB T2N 1N4, CanadaDepartment of Pathology and Laboratory Medicine, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, CanadaDepartments of Mathematical and Statistical Sciences and Medical Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R7, CanadaDepartments of Human Genetics and Urology, and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USADepartments of Human Genetics and Urology, and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USADepartment of Pathology and Laboratory Medicine, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, CanadaArsenite-resistance protein 2, also known as serrate RNA effector molecule (ARS2/SRRT), is known to be involved in cellular proliferation and tumorigenicity. However, its role in prostate cancer (PCa) has not yet been established. We investigated the potential role of SRRT in 496 prostate samples including benign, incidental, advanced, and castrate-resistant patients treated by androgen deprivation therapy (ADT). We also explored the association of SRRT with common genetic aberrations in lethal PCa using immunohistochemistry (IHC) and performed a detailed analysis of SRRT expression using The Cancer Genome Atlas (TCGA PRAD) by utilizing RNA-seq, clinical information (pathological T category and pathological Gleason score). Our findings indicated that high SRRT expression was significantly associated with poor overall survival (OS) and cause-specific survival (CSS). SRRT expression was also significantly associated with common genomic aberrations in lethal PCa such as PTEN loss, ERG gain, mutant TP53, or ATM. Furthermore, TCGA PRAD data revealed that high SRRT mRNA expression was significantly associated with higher Gleason scores, PSA levels, and T pathological categories. Gene set enrichment analysis (GSEA) of RNAseq data from the TCGA PRAD cohort indicated that <i>SRRT</i> may play a potential role in regulating the expression of genes involved in prostate cancer aggressiveness. Conclusion: The current data identify the SRRT’s potential role as a prognostic for lethal PCa, and further research is required to investigate its potential as a therapeutic target.https://www.mdpi.com/2072-6694/15/10/2867ARS2/SRRT (arsenite-resistance protein 2/serrate RNA effector molecule)ERGPTENTP53ATMlethal prostate cancer |
| spellingShingle | Yaser Gamallat Muhammad Choudhry Qiaowang Li Jon George Rokne Reda Alhajj Ramy Abdelsalam Sunita Ghosh Jaron Arbet Paul C. Boutros Tarek A. Bismar Serrate RNA Effector Molecule (SRRT) Is Associated with Prostate Cancer Progression and Is a Predictor of Poor Prognosis in Lethal Prostate Cancer Cancers ARS2/SRRT (arsenite-resistance protein 2/serrate RNA effector molecule) ERG PTEN TP53 ATM lethal prostate cancer |
| title | Serrate RNA Effector Molecule (SRRT) Is Associated with Prostate Cancer Progression and Is a Predictor of Poor Prognosis in Lethal Prostate Cancer |
| title_full | Serrate RNA Effector Molecule (SRRT) Is Associated with Prostate Cancer Progression and Is a Predictor of Poor Prognosis in Lethal Prostate Cancer |
| title_fullStr | Serrate RNA Effector Molecule (SRRT) Is Associated with Prostate Cancer Progression and Is a Predictor of Poor Prognosis in Lethal Prostate Cancer |
| title_full_unstemmed | Serrate RNA Effector Molecule (SRRT) Is Associated with Prostate Cancer Progression and Is a Predictor of Poor Prognosis in Lethal Prostate Cancer |
| title_short | Serrate RNA Effector Molecule (SRRT) Is Associated with Prostate Cancer Progression and Is a Predictor of Poor Prognosis in Lethal Prostate Cancer |
| title_sort | serrate rna effector molecule srrt is associated with prostate cancer progression and is a predictor of poor prognosis in lethal prostate cancer |
| topic | ARS2/SRRT (arsenite-resistance protein 2/serrate RNA effector molecule) ERG PTEN TP53 ATM lethal prostate cancer |
| url | https://www.mdpi.com/2072-6694/15/10/2867 |
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