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Clinical prognostic implications of EPB41L4A expression in multiple myeloma.

ABSTRACT: Background: Multiple myeloma (MM) is one of the most common incurable malignancies in malignant plasma cell disease. EPB41L4A is a target gene for the Wnt/?-catenin pathway, which is closely related to the survival of multiple myeloma cells. However, there is currently no research report on the prognostic significance of the EPB41L4A gene in MM. Methods: We studied the biological significance and prognostic significance of EPB41L4A expression in MM by integrating 1956 MM samples from 7 datasets, and explored the relationship between EPB41L4A expression and MM ISS stage, molecular type, therapeutic response and survival. Results: We found that the expression level of EPB41L4A is inversely proportional to the copy number of 1q21 (P = 3.4e-13). EPB41L4A was low expressed in MAF, MMSET and proliferating molecular typing patients (P <= 0.001). High expression of EPB41L4A can predict good survival in MM (EFS: P < 0.0001; OS: P < 0.0001). We found that patients with relapsed MM had lower expression levels of EPB41L4A than those without recurrence (P = 0.0039). We also found that EPB41L4A can predict the prognosis of MM patients may be related to DNA replication. These results indicate that the initial expression level of EPB41L4A can predict the prognosis of MM patients. Conclusions: We found that the high expression of EPB41L4A predicts good survival level in MM.

SUBMITTER: Zhang W

PROVIDER: S-EPMC6959044 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Clinical prognostic implications of EPB41L4A expression in multiple myeloma.

Zhang Weilong W Lai Rui R He Xue X Liu Xiaoni X Zhang Ye Y Yang Zuozhen Z Yang Ping P Wang Jing J Hu Kai K Yuan Xiaoliang X Zhang Xiuru X Liu Weiyou W Jing Hongmei H

Journal of Cancer 20200101 3

<b>Background:</b> Multiple myeloma (MM) is one of the most common incurable malignancies in malignant plasma cell disease. EPB41L4A is a target gene for the Wnt/β-catenin pathway, which is closely related to the survival of multiple myeloma cells. However, there is currently no research report on the prognostic significance of the EPB41L4A gene in MM. <b>Methods:</b> We studied the biological significance and prognostic significance of EPB41L4A expression in MM by integrating 1956 MM samples fr ...[more]

PMID: 31942185

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Project description:BackgroundWith the rapid development of next-generation sequencing (NGS) technologies, researchers are making efforts to reveal the genomic landscape of multiple myeloma (MM). However, the clinical significance of many mutations remains poorly defined due to the genetic heterogeneity of MM. To systematically explore the clinical implications of gene mutations and build practical prognostic models, we performed DNA sequencing in newly diagnosed MM patients.MethodsMM cells were purified from bone marrow aspirates using CD138 microbeads and subjected to sequencing with a 387-gene Panel. Nomogram was developed using Cox's proportional hazards model, and candidate variables were screened by stepwise regression. Internal validation was carried out by the bootstrap method.ResultsBetween July 2016 and December 2020, a total of 147 patients were included in our study. We found patients with a higher mutational load had a significantly shorter progress-free survival (PFS) (19.0 vs. 32.0 months, P = 0.0098) and overall survival (OS) (3-year OS rates were 66.1% and 80.0%, P = 0.0290). Mutations in chromatin regulators (CRs) including KMT2C (14.3%), KMT2D (14.3%), EP300 (11.6%) and ARID gene family (31.3%) were highly frequent in newly diagnosed MM patients. Interestingly, proteins encoded by these genes could form a complex called KMT2C/D COMPASS (KCDCOMs). Patients with mutations of ARID gene family had a significantly shorter PFS (15.5 vs. 34.0 months, P = 0.0003) and OS (3-year OS rates were 64.9% and 81.0%, P = 0.0351) than patients without ARID gene mutations. Incorporating ARID gene mutations into the current staging system could successfully improve their prognostic performance. The PFS and OS nomogram models (including 1q21 copies, ARID gene mutations, extramedullary disease, mutational load and TP53 mutations) showed good predicting performance in both training and validation sets.ConclusionOur findings emphasized the importance of CRs mutations in newly diagnosed MM patients and indicated the mutations affecting KCDCOMs might promote the development of MM. High mutational load and harboring mutations in the ARID gene family were novel predictors of adverse prognosis in MM. Prognostic models based on gene mutations were commendably prognostic evaluation methods that could provide a reference for clinical practices.

Dataset Information

Clinical prognostic implications of EPB41L4A expression in multiple myeloma.

Publications

Clinical prognostic implications of EPB41L4A expression in multiple myeloma.

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