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Prognostic Significance of Amino Acid Metabolism-Related Genes in Prostate Cancer Retrieved by Machine Learning

SIMPLE SUMMARY: Prostate cancer is a highly heterogenous disease with respect to molecular, morphological and clinical features. Therefore, one of the major tasks in its management is to define the risk subgroups that would guide the treatment approach. Amino acid metabolism-related genes are involv...

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Autores principales: Samaržija, Ivana, Trošelj, Koraljka Gall, Konjevoda, Paško
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954451/
https://www.ncbi.nlm.nih.gov/pubmed/36831650
http://dx.doi.org/10.3390/cancers15041309
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author Samaržija, Ivana
Trošelj, Koraljka Gall
Konjevoda, Paško
author_facet Samaržija, Ivana
Trošelj, Koraljka Gall
Konjevoda, Paško
author_sort Samaržija, Ivana
collection PubMed
description SIMPLE SUMMARY: Prostate cancer is a highly heterogenous disease with respect to molecular, morphological and clinical features. Therefore, one of the major tasks in its management is to define the risk subgroups that would guide the treatment approach. Amino acid metabolism-related genes are involved in several aspects of prostate cancer progression. In this publication, we show that their expression is highly aberrant in prostate cancer, which could be potentially exploited for the establishment of disease progression parameters and therapeutic targets. We show that among the variables studied, the Gleason score was the strongest prognostic factor of progression-free survival in multivariate analysis. Additionally, the expression of SERINC3 and CSAD genes strongly differentiated between better and worse prognosis (low and high risk) for high and low Gleason scores, respectively. These results offer a suggestion for potential biomarkers of prostate cancer progression in patients that are stratified by the Gleason score. ABSTRACT: Prostate cancer is among the leading cancers according to both incidence and mortality. Due to the high molecular, morphological and clinical heterogeneity, the course of prostate cancer ranges from slow growth that usually does not require immediate therapeutic intervention to aggressive and fatal disease that spreads quickly. However, currently available biomarkers cannot precisely predict the course of a disease, and novel strategies are needed to guide prostate cancer management. Amino acids serve numerous roles in cancers, among which are energy production, building block reservoirs, maintenance of redox homeostasis, epigenetic regulation, immune system modulation and resistance to therapy. In this article, by using The Cancer Genome Atlas (TCGA) data, we found that the expression of amino acid metabolism-related genes is highly aberrant in prostate cancer, which holds potential to be exploited in biomarker design or in treatment strategies. This change in expression is especially evident for catabolism genes and transporters from the solute carrier family. Furthermore, by using recursive partitioning, we confirmed that the Gleason score is strongly prognostic for progression-free survival. However, the expression of the genes SERINC3 (phosphatidylserine and sphingolipids generation) and CSAD (hypotaurine generation) can refine prognosis for high and low Gleason scores, respectively. Therefore, our results hold potential for novel prostate cancer progression biomarkers.
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spelling pubmed-99544512023-02-25 Prognostic Significance of Amino Acid Metabolism-Related Genes in Prostate Cancer Retrieved by Machine Learning Samaržija, Ivana Trošelj, Koraljka Gall Konjevoda, Paško Cancers (Basel) Article SIMPLE SUMMARY: Prostate cancer is a highly heterogenous disease with respect to molecular, morphological and clinical features. Therefore, one of the major tasks in its management is to define the risk subgroups that would guide the treatment approach. Amino acid metabolism-related genes are involved in several aspects of prostate cancer progression. In this publication, we show that their expression is highly aberrant in prostate cancer, which could be potentially exploited for the establishment of disease progression parameters and therapeutic targets. We show that among the variables studied, the Gleason score was the strongest prognostic factor of progression-free survival in multivariate analysis. Additionally, the expression of SERINC3 and CSAD genes strongly differentiated between better and worse prognosis (low and high risk) for high and low Gleason scores, respectively. These results offer a suggestion for potential biomarkers of prostate cancer progression in patients that are stratified by the Gleason score. ABSTRACT: Prostate cancer is among the leading cancers according to both incidence and mortality. Due to the high molecular, morphological and clinical heterogeneity, the course of prostate cancer ranges from slow growth that usually does not require immediate therapeutic intervention to aggressive and fatal disease that spreads quickly. However, currently available biomarkers cannot precisely predict the course of a disease, and novel strategies are needed to guide prostate cancer management. Amino acids serve numerous roles in cancers, among which are energy production, building block reservoirs, maintenance of redox homeostasis, epigenetic regulation, immune system modulation and resistance to therapy. In this article, by using The Cancer Genome Atlas (TCGA) data, we found that the expression of amino acid metabolism-related genes is highly aberrant in prostate cancer, which holds potential to be exploited in biomarker design or in treatment strategies. This change in expression is especially evident for catabolism genes and transporters from the solute carrier family. Furthermore, by using recursive partitioning, we confirmed that the Gleason score is strongly prognostic for progression-free survival. However, the expression of the genes SERINC3 (phosphatidylserine and sphingolipids generation) and CSAD (hypotaurine generation) can refine prognosis for high and low Gleason scores, respectively. Therefore, our results hold potential for novel prostate cancer progression biomarkers. MDPI 2023-02-18 /pmc/articles/PMC9954451/ /pubmed/36831650 http://dx.doi.org/10.3390/cancers15041309 Text en © 2023 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
Samaržija, Ivana
Trošelj, Koraljka Gall
Konjevoda, Paško
Prognostic Significance of Amino Acid Metabolism-Related Genes in Prostate Cancer Retrieved by Machine Learning
title Prognostic Significance of Amino Acid Metabolism-Related Genes in Prostate Cancer Retrieved by Machine Learning
title_full Prognostic Significance of Amino Acid Metabolism-Related Genes in Prostate Cancer Retrieved by Machine Learning
title_fullStr Prognostic Significance of Amino Acid Metabolism-Related Genes in Prostate Cancer Retrieved by Machine Learning
title_full_unstemmed Prognostic Significance of Amino Acid Metabolism-Related Genes in Prostate Cancer Retrieved by Machine Learning
title_short Prognostic Significance of Amino Acid Metabolism-Related Genes in Prostate Cancer Retrieved by Machine Learning
title_sort prognostic significance of amino acid metabolism-related genes in prostate cancer retrieved by machine learning
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954451/
https://www.ncbi.nlm.nih.gov/pubmed/36831650
http://dx.doi.org/10.3390/cancers15041309
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