A prognostic gene model of immune cell infiltration in diffuse large B-cell lymphoma
Background Immune cells in the tumor microenvironment are an important prognostic indicator in diffuse large B-cell lymphoma (DLBCL). However, information on the heterogeneity and risk stratification of these cells is limited. We sought to develop a novel immune model to evaluate the prognostic intr...
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PeerJ Inc.
2020-08-01
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| _version_ | 1797419997560045568 |
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| author | Hao Zhou Chang Zheng De-Sheng Huang |
| author_facet | Hao Zhou Chang Zheng De-Sheng Huang |
| author_sort | Hao Zhou |
| collection | DOAJ |
| description | Background Immune cells in the tumor microenvironment are an important prognostic indicator in diffuse large B-cell lymphoma (DLBCL). However, information on the heterogeneity and risk stratification of these cells is limited. We sought to develop a novel immune model to evaluate the prognostic intra-tumoral immune landscape of patients with DLBCL. Methods The ESTIMATE and CIBERSORT algorithms were used to estimate the numbers of 22 infiltrating immune cells based on the gene expression profiles of 229 patients with DLBCL who were recruited from a public database. The least absolute shrinkage and selection operator (Lasso) penalized regression analyses and nomogram model were used to construct and evaluate the prognostic immunoscore (PIS) model for overall survival prediction. An immune gene prognostic score (IGPS) was generated by Gene Set Enrichment Analysis (GSEA) and Cox regression analysis was and validated in an independent NCBI GEO dataset (GSE10846). Results A higher proportion of activated natural killer cells was associated with a poor outcome. A total of five immune cells were selected in the Lasso model and DLBCL patients with high PIS showed a poor prognosis (hazard ratio (HR) 2.16; 95% CI [1.33–3.50]; P = 0.002). Differences in immunoscores and their related outcomes were attributed to eight specific immune genes involved in the cytokine–cytokine receptor interaction and chemokine signaling pathways. The IGPS based on a weighted formula of eight genes is an independent prognostic factor (HR: 2.14, 95% CI [1.40–3.28]), with high specificity and sensitivity in the validation dataset. Conclusions Our findings showed that a PIS model based on immune cells is associated with the prognosis of DLBCL. We developed a novel immune-related gene-signature model associated with the PIS model and enhanced the prognostic functionality for the prediction of overall survival in patients with DLBCL. |
| first_indexed | 2024-03-09T06:56:13Z |
| format | Article |
| id | doaj.art-8392536a8b1a4fbd87543bc913c2b67c |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:56:13Z |
| publishDate | 2020-08-01 |
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| spelling | doaj.art-8392536a8b1a4fbd87543bc913c2b67c2023-12-03T10:03:54ZengPeerJ Inc.PeerJ2167-83592020-08-018e965810.7717/peerj.9658A prognostic gene model of immune cell infiltration in diffuse large B-cell lymphomaHao Zhou0Chang Zheng1De-Sheng Huang2Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, ChinaDepartment of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, ChinaDepartment of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, ChinaBackground Immune cells in the tumor microenvironment are an important prognostic indicator in diffuse large B-cell lymphoma (DLBCL). However, information on the heterogeneity and risk stratification of these cells is limited. We sought to develop a novel immune model to evaluate the prognostic intra-tumoral immune landscape of patients with DLBCL. Methods The ESTIMATE and CIBERSORT algorithms were used to estimate the numbers of 22 infiltrating immune cells based on the gene expression profiles of 229 patients with DLBCL who were recruited from a public database. The least absolute shrinkage and selection operator (Lasso) penalized regression analyses and nomogram model were used to construct and evaluate the prognostic immunoscore (PIS) model for overall survival prediction. An immune gene prognostic score (IGPS) was generated by Gene Set Enrichment Analysis (GSEA) and Cox regression analysis was and validated in an independent NCBI GEO dataset (GSE10846). Results A higher proportion of activated natural killer cells was associated with a poor outcome. A total of five immune cells were selected in the Lasso model and DLBCL patients with high PIS showed a poor prognosis (hazard ratio (HR) 2.16; 95% CI [1.33–3.50]; P = 0.002). Differences in immunoscores and their related outcomes were attributed to eight specific immune genes involved in the cytokine–cytokine receptor interaction and chemokine signaling pathways. The IGPS based on a weighted formula of eight genes is an independent prognostic factor (HR: 2.14, 95% CI [1.40–3.28]), with high specificity and sensitivity in the validation dataset. Conclusions Our findings showed that a PIS model based on immune cells is associated with the prognosis of DLBCL. We developed a novel immune-related gene-signature model associated with the PIS model and enhanced the prognostic functionality for the prediction of overall survival in patients with DLBCL.https://peerj.com/articles/9658.pdfDiffuse large B-cell lymphomaImmune cellsImmunoscoreTumor microenvironmentNatural killer cellCIBERSORT algorithm |
| spellingShingle | Hao Zhou Chang Zheng De-Sheng Huang A prognostic gene model of immune cell infiltration in diffuse large B-cell lymphoma PeerJ Diffuse large B-cell lymphoma Immune cells Immunoscore Tumor microenvironment Natural killer cell CIBERSORT algorithm |
| title | A prognostic gene model of immune cell infiltration in diffuse large B-cell lymphoma |
| title_full | A prognostic gene model of immune cell infiltration in diffuse large B-cell lymphoma |
| title_fullStr | A prognostic gene model of immune cell infiltration in diffuse large B-cell lymphoma |
| title_full_unstemmed | A prognostic gene model of immune cell infiltration in diffuse large B-cell lymphoma |
| title_short | A prognostic gene model of immune cell infiltration in diffuse large B-cell lymphoma |
| title_sort | prognostic gene model of immune cell infiltration in diffuse large b cell lymphoma |
| topic | Diffuse large B-cell lymphoma Immune cells Immunoscore Tumor microenvironment Natural killer cell CIBERSORT algorithm |
| url | https://peerj.com/articles/9658.pdf |
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