Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma

Background Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignancy with varied outcomes. However, the fundamental mechanisms remain to be fully defined. Aim We aimed to identify core differentially co-expressed hub genes and perturbed pathways relevant to the pathogenesis and prog...

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Autores principales:	Alice Charwudzi, Ye Meng, Linhui Hu, Chen Ding, Lianfang Pu, Qian Li, Mengling Xu, Zhimin Zhai, Shudao Xiong
Formato:	article
Lenguaje:	EN
Publicado:	PeerJ Inc. 2021
Materias:	Diffuse large B-cell lymphoma Integrated bioinformatic analysis Hub genes Ribosome COVID-19 Immune cells Medicine R
Acceso en línea:	https://doaj.org/article/c0442a6e4e49405794b5b2489b441f66
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spelling	oai:doaj.org-article:c0442a6e4e49405794b5b2489b441f662021-11-04T15:05:26ZIntegrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma10.7717/peerj.123942167-8359https://doaj.org/article/c0442a6e4e49405794b5b2489b441f662021-11-01T00:00:00Zhttps://peerj.com/articles/12394.pdfhttps://peerj.com/articles/12394/https://doaj.org/toc/2167-8359Background Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignancy with varied outcomes. However, the fundamental mechanisms remain to be fully defined. Aim We aimed to identify core differentially co-expressed hub genes and perturbed pathways relevant to the pathogenesis and prognosis of DLBCL. Methods We retrieved the raw gene expression profile and clinical information of GSE12453 from the Gene Expression Omnibus (GEO) database. We used integrated bioinformatics analysis to identify differentially co-expressed genes. The CIBERSORT analysis was also applied to predict tumor-infiltrating immune cells (TIICs) in the GSE12453 dataset. We performed survival and ssGSEA (single-sample Gene Set Enrichment Analysis) (for TIICs) analyses and validated the hub genes using GEPIA2 and an independent GSE31312 dataset. Results We identified 46 differentially co-expressed hub genes in the GSE12453 dataset. Gene expression levels and survival analysis found 15 differentially co-expressed core hub genes. The core genes prognostic values and expression levels were further validated in the GEPIA2 database and GSE31312 dataset to be reliable (p < 0.01). The core genes’ main KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichments were Ribosome and Coronavirus disease-COVID-19. High expressions of the 15 core hub genes had prognostic value in DLBCL. The core genes showed significant predictive accuracy in distinguishing DLBCL cases from non-tumor controls, with the area under the curve (AUC) ranging from 0.992 to 1.00. Finally, CIBERSORT analysis on GSE12453 revealed immune cells, including activated memory CD4+ T cells and M0, M1, and M2-macrophages as the infiltrates in the DLBCL microenvironment. Conclusion Our study found differentially co-expressed core hub genes and relevant pathways involved in ribosome and COVID-19 disease that may be potential targets for prognosis and novel therapeutic intervention in DLBCL.Alice CharwudziYe MengLinhui HuChen DingLianfang PuQian LiMengling XuZhimin ZhaiShudao XiongPeerJ Inc.articleDiffuse large B-cell lymphomaIntegrated bioinformatic analysisHub genesRibosomeCOVID-19Immune cellsMedicineRENPeerJ, Vol 9, p e12394 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diffuse large B-cell lymphoma Integrated bioinformatic analysis Hub genes Ribosome COVID-19 Immune cells Medicine R
spellingShingle	Diffuse large B-cell lymphoma Integrated bioinformatic analysis Hub genes Ribosome COVID-19 Immune cells Medicine R Alice Charwudzi Ye Meng Linhui Hu Chen Ding Lianfang Pu Qian Li Mengling Xu Zhimin Zhai Shudao Xiong Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma
description	Background Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignancy with varied outcomes. However, the fundamental mechanisms remain to be fully defined. Aim We aimed to identify core differentially co-expressed hub genes and perturbed pathways relevant to the pathogenesis and prognosis of DLBCL. Methods We retrieved the raw gene expression profile and clinical information of GSE12453 from the Gene Expression Omnibus (GEO) database. We used integrated bioinformatics analysis to identify differentially co-expressed genes. The CIBERSORT analysis was also applied to predict tumor-infiltrating immune cells (TIICs) in the GSE12453 dataset. We performed survival and ssGSEA (single-sample Gene Set Enrichment Analysis) (for TIICs) analyses and validated the hub genes using GEPIA2 and an independent GSE31312 dataset. Results We identified 46 differentially co-expressed hub genes in the GSE12453 dataset. Gene expression levels and survival analysis found 15 differentially co-expressed core hub genes. The core genes prognostic values and expression levels were further validated in the GEPIA2 database and GSE31312 dataset to be reliable (p < 0.01). The core genes’ main KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichments were Ribosome and Coronavirus disease-COVID-19. High expressions of the 15 core hub genes had prognostic value in DLBCL. The core genes showed significant predictive accuracy in distinguishing DLBCL cases from non-tumor controls, with the area under the curve (AUC) ranging from 0.992 to 1.00. Finally, CIBERSORT analysis on GSE12453 revealed immune cells, including activated memory CD4+ T cells and M0, M1, and M2-macrophages as the infiltrates in the DLBCL microenvironment. Conclusion Our study found differentially co-expressed core hub genes and relevant pathways involved in ribosome and COVID-19 disease that may be potential targets for prognosis and novel therapeutic intervention in DLBCL.
format	article
author	Alice Charwudzi Ye Meng Linhui Hu Chen Ding Lianfang Pu Qian Li Mengling Xu Zhimin Zhai Shudao Xiong
author_facet	Alice Charwudzi Ye Meng Linhui Hu Chen Ding Lianfang Pu Qian Li Mengling Xu Zhimin Zhai Shudao Xiong
author_sort	Alice Charwudzi
title	Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma
title_short	Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma
title_full	Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma
title_fullStr	Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma
title_full_unstemmed	Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma
title_sort	integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large b-cell lymphoma
publisher	PeerJ Inc.
publishDate	2021
url	https://doaj.org/article/c0442a6e4e49405794b5b2489b441f66
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Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma

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