Identification of key genes and multiple molecular pathways of metastatic process in prostate cancer

Background Cancer metastasis is well known as the most adverse outcome and the major cause of mortality in cancer patients, including prostate cancer (PCa). There are no credible predictors, to this day, that can reflect the metastatic ability of localized PCa. In the present study, we firstly ident...

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Main Authors: Lihuang Guo, Mingyue Lin, Zhenbo Cheng, Yi Chen, Yue Huang, Keqian Xu
Format: Article
Language:English
Published: PeerJ Inc. 2019-10-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/7899.pdf
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author Lihuang Guo
Mingyue Lin
Zhenbo Cheng
Yi Chen
Yue Huang
Keqian Xu
author_facet Lihuang Guo
Mingyue Lin
Zhenbo Cheng
Yi Chen
Yue Huang
Keqian Xu
author_sort Lihuang Guo
collection DOAJ
description Background Cancer metastasis is well known as the most adverse outcome and the major cause of mortality in cancer patients, including prostate cancer (PCa). There are no credible predictors, to this day, that can reflect the metastatic ability of localized PCa. In the present study, we firstly identified the differentially expressed genes (DEGs) and molecular pathways involved in the metastaic process of PCa by comparing gene expressions of metastaic PCa with localized PCa directly, with the purpose of identifying potential markers or therapeutic targets. Methods The gene expression profiles (GSE6919 and GSE32269) were downloaded from the Gene Expression Omnibus database, which contained 141 tissue samples, including 87 primary localized PCa samples and 54 metastaic PCa samples. After data processing, DEGs were identified by R language using the Student’s t-test adjusted via the Beniamini–Hochberg method. Subsequently, the gene ontology functional and pathway enrichment analyses of DEGs were performed and the protein–protein interaction network was constructed. Hub genes were identified using the plug-in cytoHubba in Cytoscape software by MCC and degree. Furthermore, validation and prognostic significance analysis of the hub genes were performed by UALCAN and gene expression profiling interactive analysis (GEPIA). Results A total of 90 DEGs were identified between localized and metastaic PCa, which consisted of 47 upregulated and 43 downregulated genes. The enriched functions and pathways of the DEGs include catabolic process, cell cycle, response to steroid hormone, extracellular matrix (ECM)-receptor interaction and vascular smooth muscle contraction. A total of 10 genes were identified as hub genes and biological process analysis of hub genes showed that cell cycle phase, cell division, and mitotic cell cycle process were mainly enriched. The expression of hub genes were confirmed in metastaic PCa when compared with localized PCa tissues by The Cancer Genome Atlas database. Moreover, the disease-free survival analysis of hub genes revealed that these genes may play an important role in invasion, progression or recurrence. Therefore, these hub genes might be the key genes contributed to tumor progression or metastasis in PCa and provide candidate therapeutic targets for PCa. Conclusions The present study identified some DEGs between localized and metastaic PCa tissue samples. These key genes might be potential therapeutic targets and biomarkers for the metastaic process of PCa.
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spelling doaj.art-ff00211d6d11486dabcbe94902bc62272023-12-03T10:13:46ZengPeerJ Inc.PeerJ2167-83592019-10-017e789910.7717/peerj.7899Identification of key genes and multiple molecular pathways of metastatic process in prostate cancerLihuang Guo0Mingyue Lin1Zhenbo Cheng2Yi Chen3Yue Huang4Keqian Xu5Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaDepartment of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaDepartment of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaDepartment of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaDepartment of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaDepartment of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaBackground Cancer metastasis is well known as the most adverse outcome and the major cause of mortality in cancer patients, including prostate cancer (PCa). There are no credible predictors, to this day, that can reflect the metastatic ability of localized PCa. In the present study, we firstly identified the differentially expressed genes (DEGs) and molecular pathways involved in the metastaic process of PCa by comparing gene expressions of metastaic PCa with localized PCa directly, with the purpose of identifying potential markers or therapeutic targets. Methods The gene expression profiles (GSE6919 and GSE32269) were downloaded from the Gene Expression Omnibus database, which contained 141 tissue samples, including 87 primary localized PCa samples and 54 metastaic PCa samples. After data processing, DEGs were identified by R language using the Student’s t-test adjusted via the Beniamini–Hochberg method. Subsequently, the gene ontology functional and pathway enrichment analyses of DEGs were performed and the protein–protein interaction network was constructed. Hub genes were identified using the plug-in cytoHubba in Cytoscape software by MCC and degree. Furthermore, validation and prognostic significance analysis of the hub genes were performed by UALCAN and gene expression profiling interactive analysis (GEPIA). Results A total of 90 DEGs were identified between localized and metastaic PCa, which consisted of 47 upregulated and 43 downregulated genes. The enriched functions and pathways of the DEGs include catabolic process, cell cycle, response to steroid hormone, extracellular matrix (ECM)-receptor interaction and vascular smooth muscle contraction. A total of 10 genes were identified as hub genes and biological process analysis of hub genes showed that cell cycle phase, cell division, and mitotic cell cycle process were mainly enriched. The expression of hub genes were confirmed in metastaic PCa when compared with localized PCa tissues by The Cancer Genome Atlas database. Moreover, the disease-free survival analysis of hub genes revealed that these genes may play an important role in invasion, progression or recurrence. Therefore, these hub genes might be the key genes contributed to tumor progression or metastasis in PCa and provide candidate therapeutic targets for PCa. Conclusions The present study identified some DEGs between localized and metastaic PCa tissue samples. These key genes might be potential therapeutic targets and biomarkers for the metastaic process of PCa.https://peerj.com/articles/7899.pdfLocalized prostate canerMetastaic prostate cancerMetastasisDifferentially expressed genes
spellingShingle Lihuang Guo
Mingyue Lin
Zhenbo Cheng
Yi Chen
Yue Huang
Keqian Xu
Identification of key genes and multiple molecular pathways of metastatic process in prostate cancer
PeerJ
Localized prostate caner
Metastaic prostate cancer
Metastasis
Differentially expressed genes
title Identification of key genes and multiple molecular pathways of metastatic process in prostate cancer
title_full Identification of key genes and multiple molecular pathways of metastatic process in prostate cancer
title_fullStr Identification of key genes and multiple molecular pathways of metastatic process in prostate cancer
title_full_unstemmed Identification of key genes and multiple molecular pathways of metastatic process in prostate cancer
title_short Identification of key genes and multiple molecular pathways of metastatic process in prostate cancer
title_sort identification of key genes and multiple molecular pathways of metastatic process in prostate cancer
topic Localized prostate caner
Metastaic prostate cancer
Metastasis
Differentially expressed genes
url https://peerj.com/articles/7899.pdf
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