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Identification of a novel six autophagy-related genes signature for the prognostic and a miRNA-related autophagy predictor for anti-PD-1 therapy responses in prostate cancer

BACKGROUND: Autophagy is a highly conserved homeostatic process in the human body that is responsible for the elimination of aggregated proteins and damaged organelles. Several autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer (PCa). Also, mi...

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Autores principales: Wu, Lei, Quan, Wen, Yue, Guojun, Luo, Qiong, Peng, Dongxu, Pan, Ying, Zhang, Guihai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786978/
https://www.ncbi.nlm.nih.gov/pubmed/33402116
http://dx.doi.org/10.1186/s12885-020-07725-0
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author Wu, Lei
Quan, Wen
Yue, Guojun
Luo, Qiong
Peng, Dongxu
Pan, Ying
Zhang, Guihai
author_facet Wu, Lei
Quan, Wen
Yue, Guojun
Luo, Qiong
Peng, Dongxu
Pan, Ying
Zhang, Guihai
author_sort Wu, Lei
collection PubMed
description BACKGROUND: Autophagy is a highly conserved homeostatic process in the human body that is responsible for the elimination of aggregated proteins and damaged organelles. Several autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer (PCa). Also, miRNAs have been proven to modulate autophagy by targeting some ARGs. However, their potential role in PCa still remains unclear. METHODS: An univariate Cox proportional regression model was used to identify 17 ARGs associated with the overall survival (OS) of PCa. Then, a multivariate Cox proportional regression model was used to construct a 6 autophagy-related prognostic genes signature. Patients were divided into low-risk group and high-risk group using the median risk score as a cutoff value. High-risk patients had shorter OS than low-risk patients. Furthermore, the signature was validated by ROC curves. Regarding mRNA and miRNA, 12 differentially expressed miRNAs (DEMs) and 1073 differentially expressed genes (DEGs) were detected via the GEO database. We found that miR-205, one of the DEMs, was negatively regulated the expression of ARG (NKX2–3). Based on STRING analysis results, we found that the NKX2–3 was moderately related to the part of genes among the 6 autophagy-related genes prognostic signature. Further, NKX 2–3 was significantly correlated with OS and some clinical parameters of PCa by cBioProtal. By gene set enrichment analysis (GSEA). Lastly, we demonstrated that the association between NKX2–3 and tumor mutation burden (TMB) and PDCD1 (programmed cell death 1) of PCa. RESULTS: We identified that the six ARGs expression patterns are independent predictors of OS in PCa patients. Furthermore, our results suggest that ARGs and miRNAs are inter-related. MiR-205 was negatively regulated the expression of ARG (NKX2–3). Further analysis demonstrated that NKX2–3 may be a potential biomarker for predicting the efficacy of anti-PD-1 therapy in PCa. CONCLUSIONS: The current study may offer a novel autophagy-related prognostic signature and may identify a promising miRNA-ARG pathway for predicting the efficacy of anti-PD-1 therapy in PCa.
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spelling pubmed-77869782021-01-07 Identification of a novel six autophagy-related genes signature for the prognostic and a miRNA-related autophagy predictor for anti-PD-1 therapy responses in prostate cancer Wu, Lei Quan, Wen Yue, Guojun Luo, Qiong Peng, Dongxu Pan, Ying Zhang, Guihai BMC Cancer Research Article BACKGROUND: Autophagy is a highly conserved homeostatic process in the human body that is responsible for the elimination of aggregated proteins and damaged organelles. Several autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer (PCa). Also, miRNAs have been proven to modulate autophagy by targeting some ARGs. However, their potential role in PCa still remains unclear. METHODS: An univariate Cox proportional regression model was used to identify 17 ARGs associated with the overall survival (OS) of PCa. Then, a multivariate Cox proportional regression model was used to construct a 6 autophagy-related prognostic genes signature. Patients were divided into low-risk group and high-risk group using the median risk score as a cutoff value. High-risk patients had shorter OS than low-risk patients. Furthermore, the signature was validated by ROC curves. Regarding mRNA and miRNA, 12 differentially expressed miRNAs (DEMs) and 1073 differentially expressed genes (DEGs) were detected via the GEO database. We found that miR-205, one of the DEMs, was negatively regulated the expression of ARG (NKX2–3). Based on STRING analysis results, we found that the NKX2–3 was moderately related to the part of genes among the 6 autophagy-related genes prognostic signature. Further, NKX 2–3 was significantly correlated with OS and some clinical parameters of PCa by cBioProtal. By gene set enrichment analysis (GSEA). Lastly, we demonstrated that the association between NKX2–3 and tumor mutation burden (TMB) and PDCD1 (programmed cell death 1) of PCa. RESULTS: We identified that the six ARGs expression patterns are independent predictors of OS in PCa patients. Furthermore, our results suggest that ARGs and miRNAs are inter-related. MiR-205 was negatively regulated the expression of ARG (NKX2–3). Further analysis demonstrated that NKX2–3 may be a potential biomarker for predicting the efficacy of anti-PD-1 therapy in PCa. CONCLUSIONS: The current study may offer a novel autophagy-related prognostic signature and may identify a promising miRNA-ARG pathway for predicting the efficacy of anti-PD-1 therapy in PCa. BioMed Central 2021-01-05 /pmc/articles/PMC7786978/ /pubmed/33402116 http://dx.doi.org/10.1186/s12885-020-07725-0 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Wu, Lei
Quan, Wen
Yue, Guojun
Luo, Qiong
Peng, Dongxu
Pan, Ying
Zhang, Guihai
Identification of a novel six autophagy-related genes signature for the prognostic and a miRNA-related autophagy predictor for anti-PD-1 therapy responses in prostate cancer
title Identification of a novel six autophagy-related genes signature for the prognostic and a miRNA-related autophagy predictor for anti-PD-1 therapy responses in prostate cancer
title_full Identification of a novel six autophagy-related genes signature for the prognostic and a miRNA-related autophagy predictor for anti-PD-1 therapy responses in prostate cancer
title_fullStr Identification of a novel six autophagy-related genes signature for the prognostic and a miRNA-related autophagy predictor for anti-PD-1 therapy responses in prostate cancer
title_full_unstemmed Identification of a novel six autophagy-related genes signature for the prognostic and a miRNA-related autophagy predictor for anti-PD-1 therapy responses in prostate cancer
title_short Identification of a novel six autophagy-related genes signature for the prognostic and a miRNA-related autophagy predictor for anti-PD-1 therapy responses in prostate cancer
title_sort identification of a novel six autophagy-related genes signature for the prognostic and a mirna-related autophagy predictor for anti-pd-1 therapy responses in prostate cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786978/
https://www.ncbi.nlm.nih.gov/pubmed/33402116
http://dx.doi.org/10.1186/s12885-020-07725-0
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