Pb2080: low dup1 expression predicts poor prognosis in multiple myeloma

Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: Dual-specificity phosphatase-1 (DUSP1) is one of the important members of mitogen-activated protein kinase phosphatase (MKP) family, which plays a significant role in the tumorigenesis and development of various human cancers. Aims: This study aimed to analyze the expression level in multiple myeloma (MM), to investigate the relationship between DUSP1 expression and clinicopathological characteristics of MM patients, and its prognostic significance in MM. Methods: 1. Several eligible MM microarray datasets (GSE47552, GSE24080, GSE31161, GSE2658, GSE6477 and GSE2113) was selected from the GEO database, to investigate the expression level in MM, to analyse the relationship between DUSP1 expression and clinicopathological characteristics of MM patients, and to analyze its prognostic significance in MM. 2.Clinical data and bone marrow biopsy samples was collected from 90 newly diagnosed MM patients between 2019 and 2022. Immunohistochemistry (IHC) was conducted to investigate the expression of DUSP1 protein in MM. Based on this, we analysed the relationship between DUSP1 expression and clinicopathological characteristics of MM patients, and its prognostic significance in MM. 3.Using the online tool of STRING, DUSP1 co-expression network was constructed. Correlation analyses between DUSP1 and these co-expression genes were performed. The signal pathways that DUSP1 may participate in MM were predicted by gene set enrichment analysis (GSEA). Results: 1. The data of multiple datasets from the GEO database showed that the mRNA expression of DUSP1 was significantly decreased in MM compared with normal controls and the expression of DUSP1 decreased with the evolving steps of monoclonal gammopathies. Immunohistochemistry results showed that 65.6% (59/90) of the patients with immunohistochemical scores of less than 8 were considered as low expression. 2.The data of the GSE24080 dataset showed that DUSP1 expression in MM was significantly associated with monoclonal immunoglobulin isotype (P=0.01), cytogenetic abnormality (P=0.003), ISS stage (P=0.008), R-ISS stage (P=2.20E-05), β2-microglobulin (P=0.004), C-reactive protein (P=2.540E-04), LDH (P=4.340E-09), creatinine (P=0.018), hemoglobin (P=0.049), aspirate plasma cells ratio (P=5.000E-04), and biopsy plasma cells ratio (P=9.081E-06). The data of the 90 patients showed that DUSP1 expression was significantly associated with ISS stage (P=0.019), hemoglobin (P=0.003), and serum albumin (P=0.015). 3.The data of the datasets showed that the low DUSP1 expression subgroup had inferior OS, EFS and DSS time than the high expression subgroup (P=0.004, P=0.022, P= 0.003, respectively). The data of the 90 patients showed that the low DUSP1 expression subgroup had inferior PFS time, higher complete response rate and ≥ very good partial response rate in comparison with the high expression subgroup (P=0.037, P=0.044). Summary/Conclusion: DUSP1 was significantly underexpressed in MM, predicting poor prognosis. Keywords: Multiple myeloma, Immunohistochemistry, Prognosis