Correlation Between SGK1 Expression Level and Multiple Myeloma Progression After Autologous Hematopoietic Stem Cell Transplantation
摘要
To explore the correlation between serum and glucocorticoid inducible kinase-1 (SGK1) expression levels and the multiple myeloma (MM) progression in patients after autologous stem cell transplantation (ASCT). A total of 100 MM patients who received ASCT in the Hematology Department of our hospital during January 2020 to December 2022 were selected as the research subjects. The mRNA level of SGK1 was detected by RT-PCR. Taking the median relative expression level of SGK1 mRNA (2.15) as the critical value, these subjects were divided into SGK1 high expression group (SGK1 mRNA ≥ 2.15, n = 43) and SGK1 low expression group (SGK1 mRNA < 2.15, n = 57). The expression level of SGK1 was detected by IHC. The correlation was analyzed by Spearman correlation coefficient. The survival curve drawn through Kaplan-Meier method was further verified using Log-rank test. Cox proportional hazard regression model was used for multivariate analysis to screen independent risk factors. The receiver’s working characteristic (ROC) curve was drawn to evaluate the predictive value. The H-Score was significantly higher in the SGK1 high expression group (8.52 ± 2.13) than the low expression group (3.27 ± 1.68) (t = 11.240, P < 0.001). After induction therapy, SGK1 high expression group had much lower proportion of achieving complete remission (CR), and markedly higher serum levels of β2-MG and LDH than SGK1 low expression group (P < 0.05). The expression of SGK1 in patients with partial remission (PR) was significantly higher than those with CR and very good partial remission (VGPR) (P < 0.01). Median TTP, median PFS and median OS were significantly lower in SGK1 high expression group than the SGK1 low expression group (Log-rank P < 0.01). Three months after transplantation, the positive rate of Minimal residual disease (MRD) was 48.84% (21/43) in SGK1 high expression group and 22.81% (13/57) in SGK1 low expression group (P < 0.01). The expression level of SGK1 was positively correlated with serum β2-MG (r = 0.452, P < 0.01), LDH (r = 0.388, P < 0.01), the proportion of plasma cells in bone marrow (r = 0.321, P < 0.01), and pre-transplant remission status (CR = 1, VGPR = 2, PR = 3; r = 0.413, P < 0.01), but negatively correlated with PFS (r= − 0.527, P < 0.01) and OS (r= − 0.482, P < 0.01). High SGK1 expression, serum β2-MG, and positive LDH and MRD were independent risk factors (P < 0.05). The ROC curve analysis of predicting disease progression after transplantation based on the relative expression level of SGK1 mRNA showed the area under the curve (AUC) of 0.883 (95% CI: 0.785–0.934), an optimal cutoff value of 2.18, a sensitivity of 94.32%, and a specificity of 73.63%. High expression of SGK1 was an independent risk factor for disease progression after ASCT in MM patients, which was closely related to the short survival time and high MRD positive rate. The expression level of SGK1 had a certain predictive effect on the disease progression after transplantation.
Graphical AbstractSummary of the main findings. High expression of SGK1 was an independent risk factor for disease progression after autologous stem cell transplantation in multiple myeloma patients, which was closely related to the short survival time and high minimal residual disease positive rate.