Expression analysis, clinical significance and potential function of PLXNB2 in acute myeloid leukaemia

Background The overall survival (OS) rate of adult patients suffering from acute myeloid leukaemia (AML) remains unsatisfactory at less than 40%. Current risk stratification systems fail to provide accurate guidelines for precise treatment. Novel biomarkers for predicting prognosis are urgently need...

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Veröffentlicht in:Molecular biology reports 2023-10, Vol.50 (10), p.8445-8457
Hauptverfasser: Guo, Zhibo, Guo, Dan, Kong, Desheng, Bian, Sicheng, Zhao, Linlin, Li, Qi, Lin, Leilei, Hao, Jiali, Sun, Lili, Li, Yinghua
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container_title Molecular biology reports
container_volume 50
creator Guo, Zhibo
Guo, Dan
Kong, Desheng
Bian, Sicheng
Zhao, Linlin
Li, Qi
Lin, Leilei
Hao, Jiali
Sun, Lili
Li, Yinghua
description Background The overall survival (OS) rate of adult patients suffering from acute myeloid leukaemia (AML) remains unsatisfactory at less than 40%. Current risk stratification systems fail to provide accurate guidelines for precise treatment. Novel biomarkers for predicting prognosis are urgently needed. Plexin B2 (PLXNB2), a functional receptor of angiogenin (ANG), has been found to be aberrantly expressed in multitudinous tumours. We detected overexpression of PLXNB2 mRNA in AML via transcriptome microarray analysis. This study aims to explore the potential role of PLXNB2 as a biomarker of prognosis and a prospective target of AML. Methods qRT‒PCR was conducted to verify the expression of PLXNB2 mRNA in bone marrow mononuclear cells from AML patients. Immunohistochemical and immunofluorescence staining were performed and confirmed increased expression of PLXNB2 protein in AML bone marrow tissues. Data on PLXNB2 expression, prognosis and clinical features were accessed from multiple bioinformatic databases, including The Cancer Genome Atlas (TCGA). Genes coexpressed and correlated with PLXNB2 were identified and analysed in the TCGA AML cohort. Metascape was applied for functional and pathway enrichment analysis of genes related to PLXNB2. Small molecular agents and traditional Chinese medicines potentially targeting genes related to PLXNB2 were screened via the Connectivity Map, TCMSP and HIT databases. Results PLXNB2 mRNA and protein levels are higher in AML samples than in normal controls. Overexpression of PLXNB2 is associated with worse OS in AML. Patients with high PLXNB2 expression might benefit more from haematopoietic stem cell transplantation (HSCT) (indicated by prolonged OS) than those with only chemotherapy treatment. Differentially expressed genes between the high and low PLXNB2 expression groups were overlapped with PLXNB2-coexpressed genes, and genes that overlapped were enriched in immune functions, endothelial cell regulation and cell interaction gene sets, indicating the potential function of PLXNB2 in AML. A total of 36 hub genes were identified from the differentially expressed genes, and MRC1, IL10, CD163 and CCL22 had significant prognostic value for AML. Analysis of the connectivity map and traditional agents revealed that honokiol, morphines, triptolide and paeoniflorin could be potential treatment regimens. Conclusions The overexpression of PLXNB2 is an adverse prognostic factor in adult AML patients and could be used as a potentia
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Current risk stratification systems fail to provide accurate guidelines for precise treatment. Novel biomarkers for predicting prognosis are urgently needed. Plexin B2 (PLXNB2), a functional receptor of angiogenin (ANG), has been found to be aberrantly expressed in multitudinous tumours. We detected overexpression of PLXNB2 mRNA in AML via transcriptome microarray analysis. This study aims to explore the potential role of PLXNB2 as a biomarker of prognosis and a prospective target of AML. Methods qRT‒PCR was conducted to verify the expression of PLXNB2 mRNA in bone marrow mononuclear cells from AML patients. Immunohistochemical and immunofluorescence staining were performed and confirmed increased expression of PLXNB2 protein in AML bone marrow tissues. Data on PLXNB2 expression, prognosis and clinical features were accessed from multiple bioinformatic databases, including The Cancer Genome Atlas (TCGA). Genes coexpressed and correlated with PLXNB2 were identified and analysed in the TCGA AML cohort. Metascape was applied for functional and pathway enrichment analysis of genes related to PLXNB2. Small molecular agents and traditional Chinese medicines potentially targeting genes related to PLXNB2 were screened via the Connectivity Map, TCMSP and HIT databases. Results PLXNB2 mRNA and protein levels are higher in AML samples than in normal controls. Overexpression of PLXNB2 is associated with worse OS in AML. Patients with high PLXNB2 expression might benefit more from haematopoietic stem cell transplantation (HSCT) (indicated by prolonged OS) than those with only chemotherapy treatment. Differentially expressed genes between the high and low PLXNB2 expression groups were overlapped with PLXNB2-coexpressed genes, and genes that overlapped were enriched in immune functions, endothelial cell regulation and cell interaction gene sets, indicating the potential function of PLXNB2 in AML. A total of 36 hub genes were identified from the differentially expressed genes, and MRC1, IL10, CD163 and CCL22 had significant prognostic value for AML. Analysis of the connectivity map and traditional agents revealed that honokiol, morphines, triptolide and paeoniflorin could be potential treatment regimens. Conclusions The overexpression of PLXNB2 is an adverse prognostic factor in adult AML patients and could be used as a potential biomarker. PLXNB2 might exert an oncogenic role by modulating immune functions, endothelial cell functions and cell interactions. AML patients with high PLXNB2 expression could benefit more from HSCT. Highlights PLXNB2 expression could be a potential biomarker of poor prognosis in AML. HSCT could improve the prognosis of patients with high PLXNB2 expression. PLXNB2 might regulate immunity, endothelial cells and cell interactions.</description><identifier>ISSN: 0301-4851</identifier><identifier>EISSN: 1573-4978</identifier><identifier>DOI: 10.1007/s11033-023-08721-w</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Acute myeloid leukemia ; adults ; Angiogenin ; Animal Anatomy ; Animal Biochemistry ; bioinformatics ; Biomarkers ; Biomedical and Life Sciences ; Bone marrow ; CD163 antigen ; Cell interactions ; cell transplantation ; Chemotherapy ; Clinical significance ; DNA microarrays ; drug therapy ; Endothelial cells ; fluorescent antibody technique ; Gene expression ; gene expression regulation ; genes ; Genomes ; Hematopoietic stem cells ; Histology ; honokiol ; Immunofluorescence ; immunohistochemistry ; interleukin-10 ; Leukemia ; Leukocytes (mononuclear) ; Life Sciences ; Medical prognosis ; microarray technology ; Morphology ; myeloid leukemia ; Original Article ; Patients ; Prognosis ; risk assessment ; Stem cell transplantation ; Traditional Chinese medicine ; transcriptome ; Transcriptomes ; Triptolide</subject><ispartof>Molecular biology reports, 2023-10, Vol.50 (10), p.8445-8457</ispartof><rights>The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c336t-85060d60a6def85aba6706e3fd30982f05885c8339f3168acc61a38086d8ee783</cites><orcidid>0000-0002-8060-8221</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11033-023-08721-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11033-023-08721-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids></links><search><creatorcontrib>Guo, Zhibo</creatorcontrib><creatorcontrib>Guo, Dan</creatorcontrib><creatorcontrib>Kong, Desheng</creatorcontrib><creatorcontrib>Bian, Sicheng</creatorcontrib><creatorcontrib>Zhao, Linlin</creatorcontrib><creatorcontrib>Li, Qi</creatorcontrib><creatorcontrib>Lin, Leilei</creatorcontrib><creatorcontrib>Hao, Jiali</creatorcontrib><creatorcontrib>Sun, Lili</creatorcontrib><creatorcontrib>Li, Yinghua</creatorcontrib><title>Expression analysis, clinical significance and potential function of PLXNB2 in acute myeloid leukaemia</title><title>Molecular biology reports</title><addtitle>Mol Biol Rep</addtitle><description>Background The overall survival (OS) rate of adult patients suffering from acute myeloid leukaemia (AML) remains unsatisfactory at less than 40%. Current risk stratification systems fail to provide accurate guidelines for precise treatment. Novel biomarkers for predicting prognosis are urgently needed. Plexin B2 (PLXNB2), a functional receptor of angiogenin (ANG), has been found to be aberrantly expressed in multitudinous tumours. We detected overexpression of PLXNB2 mRNA in AML via transcriptome microarray analysis. This study aims to explore the potential role of PLXNB2 as a biomarker of prognosis and a prospective target of AML. Methods qRT‒PCR was conducted to verify the expression of PLXNB2 mRNA in bone marrow mononuclear cells from AML patients. Immunohistochemical and immunofluorescence staining were performed and confirmed increased expression of PLXNB2 protein in AML bone marrow tissues. Data on PLXNB2 expression, prognosis and clinical features were accessed from multiple bioinformatic databases, including The Cancer Genome Atlas (TCGA). Genes coexpressed and correlated with PLXNB2 were identified and analysed in the TCGA AML cohort. Metascape was applied for functional and pathway enrichment analysis of genes related to PLXNB2. Small molecular agents and traditional Chinese medicines potentially targeting genes related to PLXNB2 were screened via the Connectivity Map, TCMSP and HIT databases. Results PLXNB2 mRNA and protein levels are higher in AML samples than in normal controls. Overexpression of PLXNB2 is associated with worse OS in AML. Patients with high PLXNB2 expression might benefit more from haematopoietic stem cell transplantation (HSCT) (indicated by prolonged OS) than those with only chemotherapy treatment. Differentially expressed genes between the high and low PLXNB2 expression groups were overlapped with PLXNB2-coexpressed genes, and genes that overlapped were enriched in immune functions, endothelial cell regulation and cell interaction gene sets, indicating the potential function of PLXNB2 in AML. A total of 36 hub genes were identified from the differentially expressed genes, and MRC1, IL10, CD163 and CCL22 had significant prognostic value for AML. Analysis of the connectivity map and traditional agents revealed that honokiol, morphines, triptolide and paeoniflorin could be potential treatment regimens. Conclusions The overexpression of PLXNB2 is an adverse prognostic factor in adult AML patients and could be used as a potential biomarker. PLXNB2 might exert an oncogenic role by modulating immune functions, endothelial cell functions and cell interactions. AML patients with high PLXNB2 expression could benefit more from HSCT. Highlights PLXNB2 expression could be a potential biomarker of poor prognosis in AML. HSCT could improve the prognosis of patients with high PLXNB2 expression. 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Current risk stratification systems fail to provide accurate guidelines for precise treatment. Novel biomarkers for predicting prognosis are urgently needed. Plexin B2 (PLXNB2), a functional receptor of angiogenin (ANG), has been found to be aberrantly expressed in multitudinous tumours. We detected overexpression of PLXNB2 mRNA in AML via transcriptome microarray analysis. This study aims to explore the potential role of PLXNB2 as a biomarker of prognosis and a prospective target of AML. Methods qRT‒PCR was conducted to verify the expression of PLXNB2 mRNA in bone marrow mononuclear cells from AML patients. Immunohistochemical and immunofluorescence staining were performed and confirmed increased expression of PLXNB2 protein in AML bone marrow tissues. Data on PLXNB2 expression, prognosis and clinical features were accessed from multiple bioinformatic databases, including The Cancer Genome Atlas (TCGA). Genes coexpressed and correlated with PLXNB2 were identified and analysed in the TCGA AML cohort. Metascape was applied for functional and pathway enrichment analysis of genes related to PLXNB2. Small molecular agents and traditional Chinese medicines potentially targeting genes related to PLXNB2 were screened via the Connectivity Map, TCMSP and HIT databases. Results PLXNB2 mRNA and protein levels are higher in AML samples than in normal controls. Overexpression of PLXNB2 is associated with worse OS in AML. Patients with high PLXNB2 expression might benefit more from haematopoietic stem cell transplantation (HSCT) (indicated by prolonged OS) than those with only chemotherapy treatment. Differentially expressed genes between the high and low PLXNB2 expression groups were overlapped with PLXNB2-coexpressed genes, and genes that overlapped were enriched in immune functions, endothelial cell regulation and cell interaction gene sets, indicating the potential function of PLXNB2 in AML. A total of 36 hub genes were identified from the differentially expressed genes, and MRC1, IL10, CD163 and CCL22 had significant prognostic value for AML. Analysis of the connectivity map and traditional agents revealed that honokiol, morphines, triptolide and paeoniflorin could be potential treatment regimens. Conclusions The overexpression of PLXNB2 is an adverse prognostic factor in adult AML patients and could be used as a potential biomarker. PLXNB2 might exert an oncogenic role by modulating immune functions, endothelial cell functions and cell interactions. AML patients with high PLXNB2 expression could benefit more from HSCT. Highlights PLXNB2 expression could be a potential biomarker of poor prognosis in AML. HSCT could improve the prognosis of patients with high PLXNB2 expression. PLXNB2 might regulate immunity, endothelial cells and cell interactions.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><doi>10.1007/s11033-023-08721-w</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8060-8221</orcidid></addata></record>
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subjects Acute myeloid leukemia
adults
Angiogenin
Animal Anatomy
Animal Biochemistry
bioinformatics
Biomarkers
Biomedical and Life Sciences
Bone marrow
CD163 antigen
Cell interactions
cell transplantation
Chemotherapy
Clinical significance
DNA microarrays
drug therapy
Endothelial cells
fluorescent antibody technique
Gene expression
gene expression regulation
genes
Genomes
Hematopoietic stem cells
Histology
honokiol
Immunofluorescence
immunohistochemistry
interleukin-10
Leukemia
Leukocytes (mononuclear)
Life Sciences
Medical prognosis
microarray technology
Morphology
myeloid leukemia
Original Article
Patients
Prognosis
risk assessment
Stem cell transplantation
Traditional Chinese medicine
transcriptome
Transcriptomes
Triptolide
title Expression analysis, clinical significance and potential function of PLXNB2 in acute myeloid leukaemia
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