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

ABSTRACT: 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.

SUBMITTER: Li Q

PROVIDER: S-EPMC6929508 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Li Qianru Q Zhang Liang L Jiang Jinfang J Zhang Yangyang Y Wang Xiaomeng X Zhang Qiaochu Q Wang Yang Y Liu Chunxia C Li Feng F

BMC medical genomics 20191223 1

<h4>Background</h4>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.<h4>Methods</h4>The Gene Expression Omnibus was used to sear ...[more]

PMID: 31870357

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Project description:IntroductionEssential thrombocytosis (ET) is a group of myeloproliferative neoplasms characterized by abnormal proliferation of platelet and megakaryocytes. Research on potential key genes and novel regulatory markers in essential thrombocythemia (ET) is still limited.MethodsDownloading array profiles from the Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) through comprehensive bioinformatic analysis. GO, and REACTOME pathway enrichment analysis was used to predict the potential functions of DEGs. Besides, constructing a protein-protein interaction (PPI) network through the STRING database, we validated the expression level of hub genes in an independent cohort of ET, and the transcription factors (TFs) were detected in the regulatory networks of TFs and DEGs. And the candidate drugs that are targeting hub genes were identified using the DGIdb database.ResultsWe identified 63 overlap DEGs that included 21 common up-regulated and 42 common down-regulated genes from two datasets. Functional enrichment analysis shows that the DEGs are mainly enriched in the immune system and inflammatory processes. Through PPI network analysis, ACTB, PTPRC, ACTR2, FYB, STAT1, ETS1, IL7R, IKZF1, FGL2, and CTSS were selected as hub genes. Interestingly, we found that the dysregulated hub genes are also aberrantly expressed in a bone marrow cohort of ET. Moreover, we found that the expression of CTSS, FGL2, IKZF1, STAT1, FYB, ACTR2, PTPRC, and ACTB genes were significantly under-expressed in ET (P<0.05), which is consistent with our bioinformatics analysis. The ROC curve analysis also shows that these hub genes have good diagnostic value. Besides, we identified 4 TFs (SPI1, IRF4, SRF, and AR) as master transcriptional regulators that were associated with regulating the DEGs in ET. Cyclophosphamide, prednisone, fluorouracil, ruxolitinib, and lenalidomide were predicted as potential candidate drugs for the treatment of ET.DiscussionThese dysregulated genes and predicted key regulators had a significant relationship with the occurrence of ET with affecting the immune system and inflammation of the processes. Some of the immunomodulatory drugs have potential value by targeting ACTB, PTPRC, IL7R, and IKZF1 genes in the treatment of ET.

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

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

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