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LncRNA weighted gene co-expression network analysis reveals novel biomarkers related to prostate cancer metastasis
BACKGROUND: Most prostate cancer patients die from metastasis and lack accurate efficacious biomarkers to monitor the disease behavior, optimize treatment and assess prognosis. Herein, we aimed to identify meaningful lncRNA biomarkers associated with prostate cancer metastatic progression. METHODS:...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745985/ https://www.ncbi.nlm.nih.gov/pubmed/36514044 http://dx.doi.org/10.1186/s12920-022-01410-w |
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author | Liu, Miao Chen, Man-Yun Huang, Jia-Meng Liu, Qian Wang, Lin Liu, Rong Yang, Nian Huang, Wei-Hua Zhang, Wei |
author_facet | Liu, Miao Chen, Man-Yun Huang, Jia-Meng Liu, Qian Wang, Lin Liu, Rong Yang, Nian Huang, Wei-Hua Zhang, Wei |
author_sort | Liu, Miao |
collection | PubMed |
description | BACKGROUND: Most prostate cancer patients die from metastasis and lack accurate efficacious biomarkers to monitor the disease behavior, optimize treatment and assess prognosis. Herein, we aimed to identify meaningful lncRNA biomarkers associated with prostate cancer metastatic progression. METHODS: By repurposing microarray probes, 11,624 lncRNAs in prostate cancer were obtained from Gene Expression Omnibus database (GSE46691, N = 545; GSE29079, N = 235; GSE94767, N = 130). Weighted gene co-expression network analysis was applied to determine the co-expression lncRNA network pertinent to metastasis. Hub lncRNAs were screened. RNA-seq and clinical data from the Cancer Genome Atlas prostate cancer (TCGA-PRAD) cohort (N = 531) were analyzed. Transwell assay and bioinformatic analysis were performed for mechanism research. RESULTS: The high expression levels of nine hub lncRNAs (FTX, AC005261.1, NORAD, LINC01578, AC004542.2, ZFAS1, EBLN3P, THUMPD3-AS1, GAS5) were significantly associated with Gleason score and increased probability of metastatic progression. Among these lncRNAs, ZFAS1 had the consistent trends of expression in all of the analysis from different cohorts, and the Kaplan-Meier survival analyses showed higher expression of ZFAS1 was associated with shorter relapse free survival. In-vitro studies confirmed that downregulation of ZFAS1 decreased prostate cancer cell migration. CONCLUSION: We offered some new insights into discovering lncRNA markers correlated with metastatic progression of prostate cancer using the WGCNA. Some may serve as potential prognostic biomarkers and therapeutic targets for advanced metastatic prostate cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01410-w. |
format | Online Article Text |
id | pubmed-9745985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-97459852022-12-14 LncRNA weighted gene co-expression network analysis reveals novel biomarkers related to prostate cancer metastasis Liu, Miao Chen, Man-Yun Huang, Jia-Meng Liu, Qian Wang, Lin Liu, Rong Yang, Nian Huang, Wei-Hua Zhang, Wei BMC Med Genomics Research BACKGROUND: Most prostate cancer patients die from metastasis and lack accurate efficacious biomarkers to monitor the disease behavior, optimize treatment and assess prognosis. Herein, we aimed to identify meaningful lncRNA biomarkers associated with prostate cancer metastatic progression. METHODS: By repurposing microarray probes, 11,624 lncRNAs in prostate cancer were obtained from Gene Expression Omnibus database (GSE46691, N = 545; GSE29079, N = 235; GSE94767, N = 130). Weighted gene co-expression network analysis was applied to determine the co-expression lncRNA network pertinent to metastasis. Hub lncRNAs were screened. RNA-seq and clinical data from the Cancer Genome Atlas prostate cancer (TCGA-PRAD) cohort (N = 531) were analyzed. Transwell assay and bioinformatic analysis were performed for mechanism research. RESULTS: The high expression levels of nine hub lncRNAs (FTX, AC005261.1, NORAD, LINC01578, AC004542.2, ZFAS1, EBLN3P, THUMPD3-AS1, GAS5) were significantly associated with Gleason score and increased probability of metastatic progression. Among these lncRNAs, ZFAS1 had the consistent trends of expression in all of the analysis from different cohorts, and the Kaplan-Meier survival analyses showed higher expression of ZFAS1 was associated with shorter relapse free survival. In-vitro studies confirmed that downregulation of ZFAS1 decreased prostate cancer cell migration. CONCLUSION: We offered some new insights into discovering lncRNA markers correlated with metastatic progression of prostate cancer using the WGCNA. Some may serve as potential prognostic biomarkers and therapeutic targets for advanced metastatic prostate cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01410-w. BioMed Central 2022-12-13 /pmc/articles/PMC9745985/ /pubmed/36514044 http://dx.doi.org/10.1186/s12920-022-01410-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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 Liu, Miao Chen, Man-Yun Huang, Jia-Meng Liu, Qian Wang, Lin Liu, Rong Yang, Nian Huang, Wei-Hua Zhang, Wei LncRNA weighted gene co-expression network analysis reveals novel biomarkers related to prostate cancer metastasis |
title | LncRNA weighted gene co-expression network analysis reveals novel biomarkers related to prostate cancer metastasis |
title_full | LncRNA weighted gene co-expression network analysis reveals novel biomarkers related to prostate cancer metastasis |
title_fullStr | LncRNA weighted gene co-expression network analysis reveals novel biomarkers related to prostate cancer metastasis |
title_full_unstemmed | LncRNA weighted gene co-expression network analysis reveals novel biomarkers related to prostate cancer metastasis |
title_short | LncRNA weighted gene co-expression network analysis reveals novel biomarkers related to prostate cancer metastasis |
title_sort | lncrna weighted gene co-expression network analysis reveals novel biomarkers related to prostate cancer metastasis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745985/ https://www.ncbi.nlm.nih.gov/pubmed/36514044 http://dx.doi.org/10.1186/s12920-022-01410-w |
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