Molecular background delineates outcome of double protein expressor diffuse large B-cell lymphoma

Meriranta, Leo; Pasanen, Annika; Alkodsi, Amjad; Haukka, Jari; Karjalainen–Lindsberg, Marja-Liisa; Leppä, Sirpa

doi:10.1182/bloodadvances.2020001727

Cited by 20 publications

(17 citation statements)

References 38 publications

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“…DLBCL is a highly heterogeneous tumor; clinical studies showed that DLBCL patients have multiple subtypes and different responses to the treatment of R-CHOP, which is widely recognized by clinicians[ 5 , 25 ]. As a classical example, DLBCL patients with c-Myc gene translocation have poor prognosis after R-CHOP therapy.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a five-gene signature associated with stromal infiltration for diffuse large B-cell lymphoma

Nan¹,

Zhang²,

Huang³

et al. 2021

WJCC

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BACKGROUND Diffuse large B-cell lymphoma (DLBCL) is a common non-Hodgkin lymphoma. The development of immunotherapy greatly improves the patient prognosis but there are some exceptions. Thus, screening for better biomarkers for prognostic evaluation could contribute to the treatment of DLBCL patients. AIM To screen the novel mediators involved in the development of DLBCL. METHODS The GSE60 dataset was applied to identify the differentially expressed genes (DEGs) in DLBCL, and the principal components analysis plot was used to determine the quality of the included samples. The protein-protein interactions were analyzed by the STRING tool. The key hub genes were entered into to the GEPIA database to determine their expressions in DLBCL. Furthermore, these hub gene alterations were analyzed in cBioportal. The UALCAN portal was employed to analyze the expression of the hub genes in different stages of DLBCL. The Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Score was conducted to evaluate the correlation between the gene expression and tumor purity. The gene-gene correlation analysis was conducted in the GEPIA. The stromal score analysis was conducted in TIMER to confirm the correlation between the gene expression and infiltrated stromal cells. The correlation between the indicated genes and infiltration level of cancer-associated fibroblasts (CAFs) was also completed in TIMER with two methods, MCP-Counter and Tumor immune dysfunction and exclusion. The correlation between fibronectin (FN1) protein level and secreted protein acidic and cysteine-rich (SPARC) messenger ribonucleic acid expression was confirmed in the cBioportal. RESULTS The top 20 DEGs in DLBCL were identified, and the principal components analysis plot confirmed the quality of the significant DEGs. The pairwise correlation coefficient analysis among all samples showed that these DEGs have a certain co-expression pattern. The DEGs were subjected to STRING to identify the hub genes, alpha-2-macroglobulin ( A2M ), cathepsin B ( CTSB ), FN1 , matrix metallopeptidase 9 ( MMP9 ), and SPARC . The five hub genes were confirmed to be overexpressed in DLBCL. The cBioportal portal detected these five hub genes that had gene alteration, including messenger ribonucleic acid high amplification and missense mutation, and the gene alteration percentages of A2M , FN1 , CTSB , MMP9 , and SPARC were 5%, 8%, 5%, 2.7%, and 5%, respectively. Furthermore, the five hub genes had a potential positive correlation with tumor stage. The correlation analysis between the five genes and tumor purity confirmed that the five genes were overexpressed in DLBCL and had a positi...

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Section: Discussionmentioning

confidence: 99%

Evaluation of a five-gene signature associated with stromal infiltration for diffuse large B-cell lymphoma

Nan¹,

Zhang²,

Huang³

et al. 2021

WJCC

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“…80 The underlying mechanism of DE differs among COO subgroups; within GCB, overexpression is attributed to gene re-arrangements, whereas in the ABC subgroup, overexpression represents the sequela of a complex genetic interplay involving gene amplifications and aberrations in B-cell receptor and NF-kB signaling. 77 90 Recently, the incorporation of CD37, MYC, and BCL2 to the R-IPI has shown to augment its prognostic power. 108 The distribution of genuine and cryptic DH, DE, and DHITsig +ve cases among GCB and ABC subgroups along with their overlap is depicted in Figure 3.…”

Section: Double-hit Triple-hit and Double-expressor Lymphomasmentioning

confidence: 99%

“…74,75 BCL2 overexpression has retained its prognostic ability solely within the GCB subgroup. 76,77 MYC rearrangements can be identified in 5-14% of DBCL patients, and more commonly with the GCB subgroup. 78 The rearrangement t(8;14) (q24;q32) represents the most typical, bridging MYC to the immunoglobulin heavy chain gene locus; however, in 53% of these cases, the partner is not an immunoglobulin (IG) gene.…”

Section: Double-hit Triple-hit and Double-expressor Lymphomasmentioning

confidence: 99%

Prognostic molecular biomarkers in diffuse large B-cell lymphoma in the rituximab era and their therapeutic implications

Papageorgiou

Thomopoulos

Katagas

et al. 2021

Therapeutic Advances in Hematology

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Diffuse large B-cell lymphoma (DLBCL) represents a group of tumors characterized by substantial heterogeneity in terms of their pathological and biological features, a causal factor of their varied clinical outcome. This variation has persisted despite the implementation of rituximab in treatment regimens over the last 20 years. In this context, prognostic biomarkers are of great importance in order to identify high-risk patients that might benefit from treatment intensification or the introduction of novel therapeutic agents. Herein, we review current knowledge on specific immunohistochemical or genetic biomarkers that might be useful in clinical practice. Gene-expression profiling is a tool of special consideration in this effort, as it has enriched our understanding of DLBCL biology and has allowed for the classification of DLBCL by cell-of-origin as well as by more elaborate molecular signatures based on distinct gene-expression profiles. These subgroups might outperform individual biomarkers in terms of prognostication; however, their use in clinical practice is still limited. Moreover, the underappreciated role of the tumor microenvironment in DLBCL prognosis is discussed in terms of prognostic gene-expression signatures, as well as in terms of individual biomarkers of prognostic significance. Finally, the efficacy of novel therapeutic agents for the treatment of DLBCL patients are discussed and an evidence-based therapeutic approach by specific genetic subgroup is suggested.

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“…Diffuse large B cell lymphoma (DLBCL) is a malignant tumor composed of large B lymphoid cells with a diffuse growth pattern. DLBCL has obvious heterogeneity and invasiveness, mainly divided into germinal center B-cell type (GCB), activated B-cell type (ABC) and unclassified type (UNC) [ 1 , 2 ]. GCB-DLBCL is believed to originate from germinal center blasts and is characterized by high expression of BCL6 and high frequency mutations in immunoglobulin genes [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of super enhancer-associated key genes for prognosis of germinal center B-cell type diffuse large B-cell lymphoma by integrated analysis

Duan

Hao

2021

BMC Med Genomics

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Background The pathogenesis of germinal center B-cell type diffuse large B-cell lymphoma (GCB-DLBCL) is not fully elucidated. This study aims to explore the regulation of super enhancers (SEs) on GCB-DLBCL by identifying specific SE-target gene. Methods Weighted gene co-expression network analysis (WGCNA) was used to screen modules associated with GCB subtype. Functional analysis was performed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. H3K27ac peaks were used to identify SEs. Overall survival analysis was performed using Kaplan–Meier curve with log-rank and Breslow test. The effect of ADNP, ANKRD28 and RTN4IP1 knockdown on Karpas 422 and SUDHL-4 cells proliferation was analyzed by CCK-8. Karpas 422 and SUDHL-4 cells were treated with bromodomain and extra-terminal domain (BET) inhibitor JQ1, and the expression of ADNP, ANKRD28 and RTN4IP1was measured by qRT-PCR. Results A total of 26 modules were screened in DLBCL. Turquoise module was closely related to GCB-DLBCL, and its eigengenes were mainly related to autophagy. There were 971 SEs in Karpas 422 cell and 1088 SEs in SUDHL-4 cell. Function of the nearest genes of overall SEs were related to cancer. Six SE-related genes associated with GCB-DLBCL were identified as prognostic markers. Knockdown of ADNP, ANKRD28 and RTN4IP1 inhibited the proliferation of Karpas 422 and SUDHL-4 cells. JQ1 treatment suppressed ADNP, ANKRD28 and RTN4IP1 expression in Karpas 422 and SUDHL-4 cells. Conclusions A total of 6 SE-related genes associated with GCB-DLBCL overall survival were identified in this study. These results will serve as a theoretical basis for further study of gene regulation and function of GCB-DLBCL.

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Molecular background delineates outcome of double protein expressor diffuse large B-cell lymphoma

Cited by 20 publications

References 38 publications

Evaluation of a five-gene signature associated with stromal infiltration for diffuse large B-cell lymphoma

Evaluation of a five-gene signature associated with stromal infiltration for diffuse large B-cell lymphoma

Prognostic molecular biomarkers in diffuse large B-cell lymphoma in the rituximab era and their therapeutic implications

Identification of super enhancer-associated key genes for prognosis of germinal center B-cell type diffuse large B-cell lymphoma by integrated analysis

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