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

Alice Charwudzi; Ye Meng; Linhui Hu; Chen Ding; Lianfang Pu; Qian Li; Mengling Xu; Zhimin Zhai; Shudao Xiong

doi:10.7717/peerj.12394

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

PeerJ. 2021 Nov 2:9:e12394. doi: 10.7717/peerj.12394. eCollection 2021.

Authors

Alice Charwudzi^#¹, Ye Meng^#¹, Linhui Hu¹, Chen Ding¹, Lianfang Pu¹, Qian Li¹, Mengling Xu¹, Zhimin Zhai¹, Shudao Xiong¹

Affiliation

¹ Department of Hematology/Hematological Lab, The Second Hospital of Anhui Medical University, Hefei, Anhui, China.

^# Contributed equally.

Abstract

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.

Keywords: COVID-19; Diffuse large B-cell lymphoma; Hub genes; Immune cells; Integrated bioinformatic analysis; Ribosome.

Grants and funding

This work was supported by grants from the Key Research and Development Plan of Anhui Province, China (grant number 201904a07020058); National Science Foundation of China (81272259, 81670179); Major Subject of Science and Technology of Anhui Province, China (grant number 201903a07020030); Higher School of Anhui Provincial Natural Science Research Project, China (KJ2018A0198); the Foundation of Anhui Medical University, China (grant number 2019xkj134); and Basic and Clinical Cooperative Research Promotion Plan of Anhui Medical University, China (2020xkjT021). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.