Dataset Information

Integrated analysis of 10 lymphoma datasets identifies E2F8 as a key regulator in Burkitt's lymphoma and mantle cell lymphoma.

ABSTRACT: Burkitt's lymphoma (BURK), diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are three main types of B-cell lymphomas. This study aimed to compare the differences of affected biological functions and pathways, as well as to explore the possible regulatory mechanisms and the potential therapeutic targets in BURK, DLBCL and MCL. We performed an integrated analysis of 10 lymphoma datasets including 352 BURK patients, 880 DLBCL patients, 216 MCL patients, and 33 controls. Our results showed that signaling pathways, amino acid metabolism and several lipid metabolism pathways varies considerably among these three types of lymphoma. Furthermore, we identified several key transcription factors (TFs) and their target genes that may promote these diseases by influencing multiple carcinogenic pathways. Among these TFs, we reported first that E2F8 displayed the most significant effects in BURK and MCL. Our results demonstrate that over-expression of E2F8 activates target genes that may promote cell cycle, mitosis, immune and other cancer related functions in BURK and MCL. Therefore, we suggest that E2F8 could be used as a biomarker and potential therapeutic target for BURK and MCL. These findings would be helpful in the study of pathogenesis, and drug discovery and also in the prognosis of B cell lymphomas.

SUBMITTER: Yang AP

PROVIDER: S-EPMC6684893 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrated analysis of 10 lymphoma datasets identifies E2F8 as a key regulator in Burkitt's lymphoma and mantle cell lymphoma.

Yang An-Ping AP Liu Leyna G LG Chen Min-Min MM Liu Fang F You Hua H Liu Lian L Yang Hua H Xun Yang Y Liu Jing J Wang Rui-Xue RX Brand David D DD Liu Dahai D Zheng Song Guo SG Li Wen-Xing WX

American journal of translational research 20190715 7

Burkitt's lymphoma (BURK), diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are three main types of B-cell lymphomas. This study aimed to compare the differences of affected biological functions and pathways, as well as to explore the possible regulatory mechanisms and the potential therapeutic targets in BURK, DLBCL and MCL. We performed an integrated analysis of 10 lymphoma datasets including 352 BURK patients, 880 DLBCL patients, 216 MCL patients, and 33 controls. Our resu ...[more]

PMID: 31396343

Similar Datasets

Project description:Breast cancer is one of the primary threats to women's health worldwide. However, the molecular mechanisms underlying the development of breast cancer remain to be fully elucidated. The present study aimed to investigate specific target gene expression profiles in breast cancer tissues in general and in different breast cancer stages, as well as to explore their functions in tumor development. For integrated analysis, a total of 5 gene expression profiling datasets for 3 different stages of breast cancer (stages I-III) were downloaded from the Gene Expression Omnibus of the National Center for Biotechnology Information. Pre-processing of these datasets was performed using the Robust Multi-array Average algorithm and global renormalization was performed for all studies. Differentially expressed genes between breast cancer patients and controls were estimated using the empirical Bayes algorithm. The Database for Annotation, Visualization and Integrated Discovery web server was used for analyzing the enrichment of the differentially expressed genes in Gene Ontology terms of the category biological process and in Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, breast cancer target genes were downloaded from the Thomson Reuters Integrity Database. We merged these target genes with the genes in breast cancer datasets. Analysis of anti-breast cancer gene networks was performed using the Genome-scale Integrated Analysis of Gene Networks in Tissues web server. The results demonstrated that the normal functions of the cell cycle, cell migration and cell adhesion were altered in all stages of breast cancer. Furthermore, 12 anti-breast cancer genes were identified to be dysregulated in at least one of the three stages. Among all of these genes, ribonucleotide reductase regulatory subunit M2 (RRM2) exhibited the highest degree of interaction with other interacting genes. Analysis of the network interactions revealed that the transcription factor of RRM2 is crucial for cancer development. Other genes, including mucin 1, progesterone receptor and cyclin-dependent kinase 5 regulatory subunit associated protein 3, also exhibited a high degree of interaction with the associated genes. In conclusion, several key anti-breast cancer genes identified in the present study are mainly associated with the regulation of the cell cycle, cell migration, cell adhesion and other cancer-associated cell functions, particularly RRM2.

Project description:BackgroundBurkitt's lymphoma is an aggressive B-cell lymphoma that occurs in children and adults and is largely curable with the use of intensive and toxic chemotherapy. Current treatments are less effective and have more severe side effects in adults and patients with immunodeficiency than in children.MethodsWe studied low-intensity treatment consisting of infused etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (EPOCH-R) in patients with untreated Burkitt's lymphoma. Two EPOCH-R regimens were tested: a standard dose-adjusted combination in human immunodeficiency virus (HIV)-negative patients (DA-EPOCH-R group) and a lower-dose short-course combination with a double dose of rituximab in HIV-positive patients (SC-EPOCH-RR group).ResultsA total of 30 consecutive patients were treated; 19 patients were in the DA-EPOCH-R group, and 11 in the SC-EPOCH-RR group. The overall median age of the patients was 33 years, and 40% were 40 years of age or older; 73% of the patients had intermediate-risk disease, and 10% had high-risk disease. The principal toxic events, fever and neutropenia, were observed during 22% of the DA-EPOCH-R treatment cycles and 10% of the SC-EPOCH-RR treatment cycles. The tumor lysis syndrome developed in 1 patient; no treatment-related deaths occurred. The median cumulative doses of doxorubicin-etoposide and cyclophosphamide administered in the SC-EPOCH-RR group were 47% and 57% lower, respectively, than those administered in the DA-EPOCH-R group. With median follow-up times of 86 months in the DA-EPOCH-R group and 73 months in the SC-EPOCH-RR group, the rates of freedom from progression of disease and overall survival were, respectively, 95% and 100% with DA-EPOCH-R and 100% and 90% with SC-EPOCH-RR. None of the patients died from Burkitt's lymphoma.ConclusionsIn this uncontrolled prospective study, low-intensity EPOCH-R-based treatment was highly effective in adults with sporadic or immunodeficiency-associated Burkitt's lymphoma. (Funded by the National Cancer Institute; ClinicalTrials.gov numbers, NCT00001337 and NCT00006436.).

Dataset Information

Integrated analysis of 10 lymphoma datasets identifies E2F8 as a key regulator in Burkitt's lymphoma and mantle cell lymphoma.

Publications

Integrated analysis of 10 lymphoma datasets identifies E2F8 as a key regulator in Burkitt's lymphoma and mantle cell lymphoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets