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An integrative bioinformatics investigation and experimental validation of chromobox family in diffuse large B-cell lymphoma

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive malignant tumors. Chromobox (CBX) family plays the role of oncogenes in various malignancies. METHODS: The transcriptional and protein levels of CBX family were confirmed by GEPIA, Oncomine, CCLE, and HPA database. Scree...

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Autores principales: Zhou, Fenling, Chen, Lu, Lu, Peng, Cao, Yuli, Deng, Cuilan, Liu, Gexiu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10331996/
https://www.ncbi.nlm.nih.gov/pubmed/37430195
http://dx.doi.org/10.1186/s12885-023-11108-6
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author Zhou, Fenling
Chen, Lu
Lu, Peng
Cao, Yuli
Deng, Cuilan
Liu, Gexiu
author_facet Zhou, Fenling
Chen, Lu
Lu, Peng
Cao, Yuli
Deng, Cuilan
Liu, Gexiu
author_sort Zhou, Fenling
collection PubMed
description BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive malignant tumors. Chromobox (CBX) family plays the role of oncogenes in various malignancies. METHODS: The transcriptional and protein levels of CBX family were confirmed by GEPIA, Oncomine, CCLE, and HPA database. Screening of co-expressed genes and gene function enrichment analysis were performed by GeneMANIA and DAVID 6.8. The prognostic value, immune cell infiltration and drug sensitivity analysis of CBX family in DLBCL were performed by Genomicscape, TIMER2.0, and GSCALite database. Confirmatory Tests of CBX family protein expression in DLBCL were performed by immunohistochemistry. RESULTS: The mRNA and protein expressions of CBX1/2/3/5/6 were higher in DLBCL tissues than control groups. Enrichment analysis showed that the functions of CBX family were mainly related to chromatin remodeling, methylation-dependent protein binding, and VEGF signaling pathway. The high mRNA expressions of CBX2/3/5/6 were identified to be associated with short overall survival (OS) in DLBCL patients. Multivariate COX regression indicated that CBX3 was independent prognostic marker. Immune infiltration analysis revealed that the mRNA expressions of CBX family (especially CBX1, CBX5, and CBX6) in DLBCL were significantly correlated with the infiltration of most immune cells (including B cells, CD8 + T cells, CD4 + T cells, neutrophils, monocytes, macrophages, and Treg cells). Meanwhile, there was a strong correlation between the expression levels of CBX1/5/6 and surface markers of immune cells, such as the widely studied PVR-like protein receptor/ligand and PDL-1 immune checkpoint. Notably, our study found that DLBCL cells with CBX1 over-expression were resistant to the common anti-tumor drugs, but CBX2/5 had two polarities. Finally, we confirmed the higher expressions of CBX1/2/3/5/6 in DLBCL tissues compared with control groups by immunohistochemistry. CONCLUSION: We provided a detailed analysis of the relationship between the CBX family and the prognosis of DLBCL. Distinguished from other studies, We found that high mRNA expressions of CBX2/3/5/6 were associated with poor prognosis in DLBCL patients, and Multivariate COX regression indicated that CBX3 was independent prognostic marker. Besides, our study also found an association between the CBX family and anti-tumour drug resistance, and provided a relationship between CBX family expression and immune cell infiltration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11108-6.
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spelling pubmed-103319962023-07-11 An integrative bioinformatics investigation and experimental validation of chromobox family in diffuse large B-cell lymphoma Zhou, Fenling Chen, Lu Lu, Peng Cao, Yuli Deng, Cuilan Liu, Gexiu BMC Cancer Research BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive malignant tumors. Chromobox (CBX) family plays the role of oncogenes in various malignancies. METHODS: The transcriptional and protein levels of CBX family were confirmed by GEPIA, Oncomine, CCLE, and HPA database. Screening of co-expressed genes and gene function enrichment analysis were performed by GeneMANIA and DAVID 6.8. The prognostic value, immune cell infiltration and drug sensitivity analysis of CBX family in DLBCL were performed by Genomicscape, TIMER2.0, and GSCALite database. Confirmatory Tests of CBX family protein expression in DLBCL were performed by immunohistochemistry. RESULTS: The mRNA and protein expressions of CBX1/2/3/5/6 were higher in DLBCL tissues than control groups. Enrichment analysis showed that the functions of CBX family were mainly related to chromatin remodeling, methylation-dependent protein binding, and VEGF signaling pathway. The high mRNA expressions of CBX2/3/5/6 were identified to be associated with short overall survival (OS) in DLBCL patients. Multivariate COX regression indicated that CBX3 was independent prognostic marker. Immune infiltration analysis revealed that the mRNA expressions of CBX family (especially CBX1, CBX5, and CBX6) in DLBCL were significantly correlated with the infiltration of most immune cells (including B cells, CD8 + T cells, CD4 + T cells, neutrophils, monocytes, macrophages, and Treg cells). Meanwhile, there was a strong correlation between the expression levels of CBX1/5/6 and surface markers of immune cells, such as the widely studied PVR-like protein receptor/ligand and PDL-1 immune checkpoint. Notably, our study found that DLBCL cells with CBX1 over-expression were resistant to the common anti-tumor drugs, but CBX2/5 had two polarities. Finally, we confirmed the higher expressions of CBX1/2/3/5/6 in DLBCL tissues compared with control groups by immunohistochemistry. CONCLUSION: We provided a detailed analysis of the relationship between the CBX family and the prognosis of DLBCL. Distinguished from other studies, We found that high mRNA expressions of CBX2/3/5/6 were associated with poor prognosis in DLBCL patients, and Multivariate COX regression indicated that CBX3 was independent prognostic marker. Besides, our study also found an association between the CBX family and anti-tumour drug resistance, and provided a relationship between CBX family expression and immune cell infiltration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11108-6. BioMed Central 2023-07-10 /pmc/articles/PMC10331996/ /pubmed/37430195 http://dx.doi.org/10.1186/s12885-023-11108-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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
Zhou, Fenling
Chen, Lu
Lu, Peng
Cao, Yuli
Deng, Cuilan
Liu, Gexiu
An integrative bioinformatics investigation and experimental validation of chromobox family in diffuse large B-cell lymphoma
title An integrative bioinformatics investigation and experimental validation of chromobox family in diffuse large B-cell lymphoma
title_full An integrative bioinformatics investigation and experimental validation of chromobox family in diffuse large B-cell lymphoma
title_fullStr An integrative bioinformatics investigation and experimental validation of chromobox family in diffuse large B-cell lymphoma
title_full_unstemmed An integrative bioinformatics investigation and experimental validation of chromobox family in diffuse large B-cell lymphoma
title_short An integrative bioinformatics investigation and experimental validation of chromobox family in diffuse large B-cell lymphoma
title_sort integrative bioinformatics investigation and experimental validation of chromobox family in diffuse large b-cell lymphoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10331996/
https://www.ncbi.nlm.nih.gov/pubmed/37430195
http://dx.doi.org/10.1186/s12885-023-11108-6
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