Abstract
Background: Multiple myeloma (MM) is one of the most common types of hematological malignance, and the prognosis of MM patients remains poor.Objective: To identify and validate a genetic prognostic signature in patients with MM.Methods: Co-expression network was constructed to identify hub genes related with International Staging System (ISS) stage of MM. Functional analysis of hub genes was conducted. Univariate Cox proportional hazard regression analysis was conducted to identify genes correlated with the overall survival (OS) of MM patients. Least absolute shrinkage and selection operator (LASSO) penalized Cox proportional hazards regression model was used to minimize overfitting and construct a prognostic signature. The prognostic value of the signature was validated in the test set and an independent validation cohort.Results: A total of 758 hub genes correlated with ISS stage of MM patients were identified, and these hub genes were mainly enriched in several GO terms and KEGG pathways involved in cell proliferation and immune response. Nine hub genes (HLA-DPB1, TOP2A, FABP5, CYP1B1, IGHM, FANCI, LYZ, HMGN5, and BEND6) with non-zero coefficients in the LASSO Cox regression model were used to build a 9-gene prognostic signature. Relapsed MM and ISS stage III MM was associated with high risk score calculated based on the signature. Patients in the 9-gene signature low risk group was significantly associated with better clinical outcome than those in the 9-gene signature high risk group in the training set, test, and validation set.Conclusions: We developed a 9-gene prognostic signature that might be an independent prognostic factor in patients with MM.
Highlights
Multiple myeloma (MM), originated from malignant plasma cells secreting monoclonal M protein, represents the second most common malignancy in hematological malignancies [1,2,3]
After co-expression network construction, a total of 780 probes were identified based on our screening criteria, 758 of which annotated to gene symbol were treated as hub genes (Supplementary Table 1)
The major process of co-expression network construction and hub gene identification was shown in Supplementary Figure 1
Summary
Multiple myeloma (MM), originated from malignant plasma cells secreting monoclonal M protein, represents the second most common malignancy in hematological malignancies [1,2,3]. MM is differentiated from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) by the presence of end-organ damage [4, 5]. The clinical outcomes of patients with MM have been significantly improved, MM remains an incurable disease and the prognosis of patients with MM remains poor (with a median survival of approximately 3–4 years) [13]. The International Staging System (ISS) stage of MM, based on β2-microglobulin (β2M) and albumin (ALB), divides MM patients into three different stages with significant dissimilar clinical outcomes. Multiple myeloma (MM) is one of the most common types of hematological malignance, and the prognosis of MM patients remains poor
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