Dataset Information

Identification of six hub genes in mantle cell lymphoma patients with BTKi resistance.

ABSTRACT:

Background

Bruton tyrosine kinase inhibitor (BTKi) resistance is an unsolved problem in the treatment of relapse/recurrence (R/R) mantle cell lymphoma (MCL). Although salvage therapy following ibrutinib resistance has been attempted in recent years, the survival of resistant patients was significantly reduced. Once ibrutinib-treated patients relapse, the 1-year survival rate is only 22%. Acquired drug resistance and primary drug resistance were found to relate closely to genetic mutations. The hub genes identification and clinical data analysis of patients resistant to BTKi based on the Chinese MCL gene mutation profile are worthy of exploration.

Methods

Based on 28 MCL patients' mutation data and clinical data, 6 hub genes were screened by a gene panel of 69 genes and univariate Cox prognostic analysis. Prognosis and responses to salvage therapy regimen were analyzed.

Results

Patients with BTKi had less favorable clinical features at baseline. Chimeric antigen receptor T-cell (CAR-T) therapy yielded the best response among salvage treatments. The 6 hub genes were screened by a gene panel of 69 genes (GP79) which might be a potential predictor for MCL patients with BTKi resistance.

Conclusions

The clinical characteristics of BTKi resistance in MCL patients were summarized, and 6 hub genes were identified to provide ideas and suggestions for further research.

SUBMITTER: Liu S

PROVIDER: S-EPMC9652540 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Identification of six hub genes in mantle cell lymphoma patients with BTKi resistance.

Liu Shuozi S Yang Ping P Wang Lingli L Li Chunyuan C Zhang Weilong W Wang Jing J Jing Hongmei H

Annals of translational medicine 20221001 20

<h4>Background</h4>Bruton tyrosine kinase inhibitor (BTKi) resistance is an unsolved problem in the treatment of relapse/recurrence (R/R) mantle cell lymphoma (MCL). Although salvage therapy following ibrutinib resistance has been attempted in recent years, the survival of resistant patients was significantly reduced. Once ibrutinib-treated patients relapse, the 1-year survival rate is only 22%. Acquired drug resistance and primary drug resistance were found to relate closely to genetic mutation ...[more]

PMID: 36388812

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Project description:PurposeMantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma that is incurable with standard therapies. The use of gene expression analysis has been of interest, recently, to detect biomarkers for cancer. There is a great need for systemic coexpression network analysis of MCL and this study aims to establish a gene coexpression network to forecast key genes related to the pathogenesis and prognosis of MCL.MethodsThe microarray dataset GSE93291 was downloaded from the Gene Expression Omnibus database. We systematically identified coexpression modules using the weighted gene coexpression network analysis method (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were performed on the modules deemed important. The protein-protein interaction networks were constructed and visualized using Cytoscape software on the basis of the STRING website; the hub genes in the top weighted network were identified. Survival data were analyzed using the Kaplan-Meier method and were compared using the log-rank test.ResultsSeven coexpression modules consisting of different genes were applied to 5,000 genes in the 121 human MCL samples using WGCNA software. GO and KEGG enrichment analysis identified the blue module as one of the most important modules; the most critical pathways identified were the ribosome, oxidative phosphorylation and proteasome pathways. The hub genes in the top weighted network were regarded as real hub genes (IL2RB, CD3D, RPL26L1, POLR2K, KIF11, CDC20, CCNB1, CCNA2, PUF60, SNRNP70, AKT1 and PRPF40A). Survival analysis revealed that seven genes (KIF11, CDC20, CCNB1, CCNA2, PRPF40A, CD3D and PUF60) were associated with overall survival time (p < 0.05).ConclusionsThe blue module may play a vital role in the pathogenesis of MCL. Five real hub genes (KIF11, CDC20, CCNB1, CCNA2 and PUF60) were identified as potential prognostic biomarkers as well as therapeutic targets with clinical utility for MCL.

Dataset Information

Identification of six hub genes in mantle cell lymphoma patients with BTKi resistance.

Background

Methods

Results

Conclusions

Publications

Identification of six hub genes in mantle cell lymphoma patients with BTKi resistance.

Similar Datasets

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