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A Novel Four Mitochondrial Respiration-Related Signature for Predicting Biochemical Recurrence of Prostate Cancer

The biochemical recurrence (BCR) of patients with prostate cancer (PCa) after radical prostatectomy is high, and mitochondrial respiration is reported to be associated with the metabolism in PCa development. This study aimed to establish a mitochondrial respiratory gene-based risk model to predict t...

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Autores principales: Xia, Zhongyou, Liu, Haolin, Fan, Shicheng, Tu, Hongtao, Jiang, Yongming, Wang, Hai, Gu, Peng, Liu, Xiaodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866444/
https://www.ncbi.nlm.nih.gov/pubmed/36675580
http://dx.doi.org/10.3390/jcm12020654
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author Xia, Zhongyou
Liu, Haolin
Fan, Shicheng
Tu, Hongtao
Jiang, Yongming
Wang, Hai
Gu, Peng
Liu, Xiaodong
author_facet Xia, Zhongyou
Liu, Haolin
Fan, Shicheng
Tu, Hongtao
Jiang, Yongming
Wang, Hai
Gu, Peng
Liu, Xiaodong
author_sort Xia, Zhongyou
collection PubMed
description The biochemical recurrence (BCR) of patients with prostate cancer (PCa) after radical prostatectomy is high, and mitochondrial respiration is reported to be associated with the metabolism in PCa development. This study aimed to establish a mitochondrial respiratory gene-based risk model to predict the BCR of PCa. RNA sequencing data of PCa were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and mitochondrial respiratory-related genes (MRGs) were sourced via GeneCards. The differentially expressed mitochondrial respiratory and BCR-related genes (DE-MR-BCRGs) were acquired through overlapping BCR-related differentially expressed genes (BCR-DEGs) and differentially expressed MRGs (DE-MRGs) between PCa samples and controls. Further, univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analyses were performed to construct a DE-MRGs-based risk model. Then, a nomogram was established by analyzing the independent prognostic factor of five clinical features and risk scores. Moreover, Gene Set Enrichment Analysis (GSEA), tumor microenvironment, and drug susceptibility analyses were employed between high- and low-risk groups of PCa patients with BCR. Finally, qRT-PCR was utilized to validate the expression of prognostic genes. We identified 11 DE-MR-BCRGs by overlapping 132 DE-MRGs and 13 BCR-DEGs and constructed a risk model consisting of 4 genes (APOE, DNAH8, EME2, and KIF5A). Furthermore, we established an accurate nomogram, including a risk score and a Gleason score, for the BCR prediction of PCa patients. The GSEA result suggested the risk model was related to the PPAR signaling pathway, the cholesterol catabolic process, the organic hydroxy compound biosynthetic process, the small molecule catabolic process, and the steroid catabolic process. Simultaneously, we found six immune cell types relevant to the risk model: resting memory CD4+ T cells, monocytes, resting mast cells, activated memory CD4+ T cells, regulatory T cells (Tregs), and macrophages M2. Moreover, the risk model could affect the IC50 of 12 cancer drugs, including Lapatinib, Bicalutamide, and Embelin. Finally, qRT-PCR showed that APOE, EME2, and DNAH8 were highly expressed in PCa, while KIF5A was downregulated in PCa. Collectively, a mitochondrial respiratory gene-based nomogram including four genes and one clinical feature was established for BCR prediction in patients with PCa, which could provide novel strategies for further studies.
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spelling pubmed-98664442023-01-22 A Novel Four Mitochondrial Respiration-Related Signature for Predicting Biochemical Recurrence of Prostate Cancer Xia, Zhongyou Liu, Haolin Fan, Shicheng Tu, Hongtao Jiang, Yongming Wang, Hai Gu, Peng Liu, Xiaodong J Clin Med Article The biochemical recurrence (BCR) of patients with prostate cancer (PCa) after radical prostatectomy is high, and mitochondrial respiration is reported to be associated with the metabolism in PCa development. This study aimed to establish a mitochondrial respiratory gene-based risk model to predict the BCR of PCa. RNA sequencing data of PCa were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and mitochondrial respiratory-related genes (MRGs) were sourced via GeneCards. The differentially expressed mitochondrial respiratory and BCR-related genes (DE-MR-BCRGs) were acquired through overlapping BCR-related differentially expressed genes (BCR-DEGs) and differentially expressed MRGs (DE-MRGs) between PCa samples and controls. Further, univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analyses were performed to construct a DE-MRGs-based risk model. Then, a nomogram was established by analyzing the independent prognostic factor of five clinical features and risk scores. Moreover, Gene Set Enrichment Analysis (GSEA), tumor microenvironment, and drug susceptibility analyses were employed between high- and low-risk groups of PCa patients with BCR. Finally, qRT-PCR was utilized to validate the expression of prognostic genes. We identified 11 DE-MR-BCRGs by overlapping 132 DE-MRGs and 13 BCR-DEGs and constructed a risk model consisting of 4 genes (APOE, DNAH8, EME2, and KIF5A). Furthermore, we established an accurate nomogram, including a risk score and a Gleason score, for the BCR prediction of PCa patients. The GSEA result suggested the risk model was related to the PPAR signaling pathway, the cholesterol catabolic process, the organic hydroxy compound biosynthetic process, the small molecule catabolic process, and the steroid catabolic process. Simultaneously, we found six immune cell types relevant to the risk model: resting memory CD4+ T cells, monocytes, resting mast cells, activated memory CD4+ T cells, regulatory T cells (Tregs), and macrophages M2. Moreover, the risk model could affect the IC50 of 12 cancer drugs, including Lapatinib, Bicalutamide, and Embelin. Finally, qRT-PCR showed that APOE, EME2, and DNAH8 were highly expressed in PCa, while KIF5A was downregulated in PCa. Collectively, a mitochondrial respiratory gene-based nomogram including four genes and one clinical feature was established for BCR prediction in patients with PCa, which could provide novel strategies for further studies. MDPI 2023-01-13 /pmc/articles/PMC9866444/ /pubmed/36675580 http://dx.doi.org/10.3390/jcm12020654 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
Xia, Zhongyou
Liu, Haolin
Fan, Shicheng
Tu, Hongtao
Jiang, Yongming
Wang, Hai
Gu, Peng
Liu, Xiaodong
A Novel Four Mitochondrial Respiration-Related Signature for Predicting Biochemical Recurrence of Prostate Cancer
title A Novel Four Mitochondrial Respiration-Related Signature for Predicting Biochemical Recurrence of Prostate Cancer
title_full A Novel Four Mitochondrial Respiration-Related Signature for Predicting Biochemical Recurrence of Prostate Cancer
title_fullStr A Novel Four Mitochondrial Respiration-Related Signature for Predicting Biochemical Recurrence of Prostate Cancer
title_full_unstemmed A Novel Four Mitochondrial Respiration-Related Signature for Predicting Biochemical Recurrence of Prostate Cancer
title_short A Novel Four Mitochondrial Respiration-Related Signature for Predicting Biochemical Recurrence of Prostate Cancer
title_sort novel four mitochondrial respiration-related signature for predicting biochemical recurrence of prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866444/
https://www.ncbi.nlm.nih.gov/pubmed/36675580
http://dx.doi.org/10.3390/jcm12020654
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