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CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis

BACKGROUND: Rhabdomyosarcoma (RMS), a common soft-tissue malignancy in pediatrics, presents high invasiveness and mortality. However, besides known changes in the PAX3/7-FOXO1 fusion gene in alveolar RMS, the molecular mechanisms of the disease remain incompletely understood. The purpose of the stud...

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Autores principales: Li, Qianru, Zhang, Liang, Jiang, Jinfang, Zhang, Yangyang, Wang, Xiaomeng, Zhang, Qiaochu, Wang, Yang, Liu, Chunxia, Li, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929508/
https://www.ncbi.nlm.nih.gov/pubmed/31870357
http://dx.doi.org/10.1186/s12920-019-0645-x
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author Li, Qianru
Zhang, Liang
Jiang, Jinfang
Zhang, Yangyang
Wang, Xiaomeng
Zhang, Qiaochu
Wang, Yang
Liu, Chunxia
Li, Feng
author_facet Li, Qianru
Zhang, Liang
Jiang, Jinfang
Zhang, Yangyang
Wang, Xiaomeng
Zhang, Qiaochu
Wang, Yang
Liu, Chunxia
Li, Feng
author_sort Li, Qianru
collection PubMed
description BACKGROUND: Rhabdomyosarcoma (RMS), a common soft-tissue malignancy in pediatrics, presents high invasiveness and mortality. However, besides known changes in the PAX3/7-FOXO1 fusion gene in alveolar RMS, the molecular mechanisms of the disease remain incompletely understood. The purpose of the study is to recognize potential biomarkers related with RMS and analyse their molecular mechanism, diagnosis and prognostic significance. METHODS: The Gene Expression Omnibus was used to search the RMS and normal striated muscle data sets. Differentially expressed genes (DEGs) were filtered using R software. The DAVID has become accustomed to performing functional annotations and pathway analysis on DEGs. The protein interaction was constructed and further processed by the STRING tool and Cytoscape software. Kaplan–Meier was used to estimate the effect of hub genes on the ending of sarcoma sufferers, and the expression of these genes in RMS was proved by real-time polymerase chain reaction (RT-PCR). Finally, the expression of CDK1 and CCNB1 in RMS was validated by immunohistochemistry (IHC). RESULTS: A total of 1932 DEGs were obtained, amongst which 1505 were up-regulated and 427were down-regulated. Up-regulated genes were largely enriched in the cell cycle, ECM-receptor interaction, PI3K/Akt and p53 pathways, whilst down-regulated genes were primarily enriched in the muscle contraction process. CDK1, CCNB1, CDC20, CCNB2, AURKB, MAD2L1, HIST2H2BE, CENPE, KIF2C and PCNA were identified as hub genes by Cytoscape analyses. Survival analysis showed that, except for HIST2H2BE, the other hub genes were highly expressed and related to poor prognosis in sarcoma. RT-PCR validation showed that CDK1, CCNB1, CDC20, CENPE and HIST2H2BE were significantly differential expression in RMS compared to the normal control. IHC revealed that the expression of CDK1 (28/32, 87.5%) and CCNB1 (26/32, 81.25%) were notably higher in RMS than normal controls (1/9, 11.1%; 0/9, 0%). Moreover, the CCNB1 was associated with the age and location of the patient’s onset. CONCLUSIONS: These results show that these hub genes, especially CDK1 and CCNB1, may be potential diagnostic biomarkers for RMS and provide a new perspective for the pathogenesis of RMS.
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spelling pubmed-69295082019-12-30 CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis Li, Qianru Zhang, Liang Jiang, Jinfang Zhang, Yangyang Wang, Xiaomeng Zhang, Qiaochu Wang, Yang Liu, Chunxia Li, Feng BMC Med Genomics Research Article BACKGROUND: Rhabdomyosarcoma (RMS), a common soft-tissue malignancy in pediatrics, presents high invasiveness and mortality. However, besides known changes in the PAX3/7-FOXO1 fusion gene in alveolar RMS, the molecular mechanisms of the disease remain incompletely understood. The purpose of the study is to recognize potential biomarkers related with RMS and analyse their molecular mechanism, diagnosis and prognostic significance. METHODS: The Gene Expression Omnibus was used to search the RMS and normal striated muscle data sets. Differentially expressed genes (DEGs) were filtered using R software. The DAVID has become accustomed to performing functional annotations and pathway analysis on DEGs. The protein interaction was constructed and further processed by the STRING tool and Cytoscape software. Kaplan–Meier was used to estimate the effect of hub genes on the ending of sarcoma sufferers, and the expression of these genes in RMS was proved by real-time polymerase chain reaction (RT-PCR). Finally, the expression of CDK1 and CCNB1 in RMS was validated by immunohistochemistry (IHC). RESULTS: A total of 1932 DEGs were obtained, amongst which 1505 were up-regulated and 427were down-regulated. Up-regulated genes were largely enriched in the cell cycle, ECM-receptor interaction, PI3K/Akt and p53 pathways, whilst down-regulated genes were primarily enriched in the muscle contraction process. CDK1, CCNB1, CDC20, CCNB2, AURKB, MAD2L1, HIST2H2BE, CENPE, KIF2C and PCNA were identified as hub genes by Cytoscape analyses. Survival analysis showed that, except for HIST2H2BE, the other hub genes were highly expressed and related to poor prognosis in sarcoma. RT-PCR validation showed that CDK1, CCNB1, CDC20, CENPE and HIST2H2BE were significantly differential expression in RMS compared to the normal control. IHC revealed that the expression of CDK1 (28/32, 87.5%) and CCNB1 (26/32, 81.25%) were notably higher in RMS than normal controls (1/9, 11.1%; 0/9, 0%). Moreover, the CCNB1 was associated with the age and location of the patient’s onset. CONCLUSIONS: These results show that these hub genes, especially CDK1 and CCNB1, may be potential diagnostic biomarkers for RMS and provide a new perspective for the pathogenesis of RMS. BioMed Central 2019-12-23 /pmc/articles/PMC6929508/ /pubmed/31870357 http://dx.doi.org/10.1186/s12920-019-0645-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.
spellingShingle Research Article
Li, Qianru
Zhang, Liang
Jiang, Jinfang
Zhang, Yangyang
Wang, Xiaomeng
Zhang, Qiaochu
Wang, Yang
Liu, Chunxia
Li, Feng
CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis
title CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis
title_full CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis
title_fullStr CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis
title_full_unstemmed CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis
title_short CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis
title_sort cdk1 and ccnb1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929508/
https://www.ncbi.nlm.nih.gov/pubmed/31870357
http://dx.doi.org/10.1186/s12920-019-0645-x
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