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Systematic Analysis of Cellular Signaling Pathways and Therapeutic Targets for SLC45A3:ERG Fusion-Positive Prostate Cancer
ETS-related gene (ERG) fusion affects prostate cancer depending on the degree of expression of ERG. Solute Carrier Family 45 Member 3 (SLC45A3) is the second-most common 5′ partner gene of ERG rearrangement. However, the molecular pathological features of SLC45A3:ERG (S:E) fusion and therapeutic met...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693845/ https://www.ncbi.nlm.nih.gov/pubmed/36579559 http://dx.doi.org/10.3390/jpm12111818 |
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author | Kim, Jongsu Hwang, Kyung Won Lee, Hye Jung Kim, Hong Sook |
author_facet | Kim, Jongsu Hwang, Kyung Won Lee, Hye Jung Kim, Hong Sook |
author_sort | Kim, Jongsu |
collection | PubMed |
description | ETS-related gene (ERG) fusion affects prostate cancer depending on the degree of expression of ERG. Solute Carrier Family 45 Member 3 (SLC45A3) is the second-most common 5′ partner gene of ERG rearrangement. However, the molecular pathological features of SLC45A3:ERG (S:E) fusion and therapeutic methods have not been studied at all. S:E fusion-positive cancers (n = 10) were selected from the Tumor Fusion Gene Data Portal website. Fusion-negative cancers (n = 50) were selected by sorting ERG expression level in descending order and selecting the bottom to 50th sample. Totally, 1325 ERG correlated genes were identified by a Pearson correlation test using over 0.3 of absolute correlation coefficiency (|R| > 0.3). Pathway analysis was performed using over-representation analysis of correlated genes, and seven cancer-related pathways (focal adhesion kinase (FAK)/PI3K-Akt, JAK-STAT, Notch, receptor tyrosine kinase/PDGF, TGF-β, VEGFA, and Wnt signaling) were identified. In particular, focal adhesion kinase (FAK)/PI3K-Akt signaling and JAK-STAT signaling were significantly enriched in S:E fusion-positive prostate cancer. We further identified therapeutic targets and candidate drugs for S:E fusion-positive prostate cancer using gene–drug network analysis. Interestingly, PDGFRA and PDGFRB were the most frequently predicted therapeutic targets, and imatinib targeted both genes. In this study, we provide extensive information on cellular signaling pathways involved in S:E fusion-positive prostate cancer and also suggest therapeutic methods. |
format | Online Article Text |
id | pubmed-9693845 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96938452022-11-26 Systematic Analysis of Cellular Signaling Pathways and Therapeutic Targets for SLC45A3:ERG Fusion-Positive Prostate Cancer Kim, Jongsu Hwang, Kyung Won Lee, Hye Jung Kim, Hong Sook J Pers Med Article ETS-related gene (ERG) fusion affects prostate cancer depending on the degree of expression of ERG. Solute Carrier Family 45 Member 3 (SLC45A3) is the second-most common 5′ partner gene of ERG rearrangement. However, the molecular pathological features of SLC45A3:ERG (S:E) fusion and therapeutic methods have not been studied at all. S:E fusion-positive cancers (n = 10) were selected from the Tumor Fusion Gene Data Portal website. Fusion-negative cancers (n = 50) were selected by sorting ERG expression level in descending order and selecting the bottom to 50th sample. Totally, 1325 ERG correlated genes were identified by a Pearson correlation test using over 0.3 of absolute correlation coefficiency (|R| > 0.3). Pathway analysis was performed using over-representation analysis of correlated genes, and seven cancer-related pathways (focal adhesion kinase (FAK)/PI3K-Akt, JAK-STAT, Notch, receptor tyrosine kinase/PDGF, TGF-β, VEGFA, and Wnt signaling) were identified. In particular, focal adhesion kinase (FAK)/PI3K-Akt signaling and JAK-STAT signaling were significantly enriched in S:E fusion-positive prostate cancer. We further identified therapeutic targets and candidate drugs for S:E fusion-positive prostate cancer using gene–drug network analysis. Interestingly, PDGFRA and PDGFRB were the most frequently predicted therapeutic targets, and imatinib targeted both genes. In this study, we provide extensive information on cellular signaling pathways involved in S:E fusion-positive prostate cancer and also suggest therapeutic methods. MDPI 2022-11-02 /pmc/articles/PMC9693845/ /pubmed/36579559 http://dx.doi.org/10.3390/jpm12111818 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kim, Jongsu Hwang, Kyung Won Lee, Hye Jung Kim, Hong Sook Systematic Analysis of Cellular Signaling Pathways and Therapeutic Targets for SLC45A3:ERG Fusion-Positive Prostate Cancer |
title | Systematic Analysis of Cellular Signaling Pathways and Therapeutic Targets for SLC45A3:ERG Fusion-Positive Prostate Cancer |
title_full | Systematic Analysis of Cellular Signaling Pathways and Therapeutic Targets for SLC45A3:ERG Fusion-Positive Prostate Cancer |
title_fullStr | Systematic Analysis of Cellular Signaling Pathways and Therapeutic Targets for SLC45A3:ERG Fusion-Positive Prostate Cancer |
title_full_unstemmed | Systematic Analysis of Cellular Signaling Pathways and Therapeutic Targets for SLC45A3:ERG Fusion-Positive Prostate Cancer |
title_short | Systematic Analysis of Cellular Signaling Pathways and Therapeutic Targets for SLC45A3:ERG Fusion-Positive Prostate Cancer |
title_sort | systematic analysis of cellular signaling pathways and therapeutic targets for slc45a3:erg fusion-positive prostate cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693845/ https://www.ncbi.nlm.nih.gov/pubmed/36579559 http://dx.doi.org/10.3390/jpm12111818 |
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