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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...

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Autores principales: Kim, Jongsu, Hwang, Kyung Won, Lee, Hye Jung, Kim, Hong Sook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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