ABSTRACT
The treatment of relapse or refractory multiple myeloma (RRMM) is still a big challenge in clinic. Recently, several clinical trials indicated that the XPO1 inhibitor, selinexor could significantly improve the remission rate in MM patients. However, the heterogeneous genetic background greatly influenced the efficiency of selinexor among MM. Here, we tried to characterized the biomarkers associated with selinexor sensitivity by analyzing gene expression data in MM patients. We found the cytogenetic background of selinexor sensitive MM patients was not limited to specific cytogenetic subtypes. In addition, by weighted gene co-expression network analysis (WGCNA), we obtained 10 key genes which showed a strong correlation with the selinexor sensitivity in MM patients. Notably, ABCC4 (MRP4) was the only gene which was both differentially expressed and proved to be clinical prognostic valuable (both for event-free survival and overall survival) in MM patients. We further validated the heterogenous expression of ABCC4 in MM cell lines and its value as a novel indicator for selinexor sensitivity. Moreover, immune infiltration analysis showed that ABCC4 expression had a significantly positive correlation with NK infiltration as well as immunotherapy target TIM-3 (HAVCR2) expression. Collectively, our findings indicated that ABCC4 might be a predictive biomarker of selinexor sensitivity in MM patients, which could be enhanced if combined with immunotherapy drugs such as TIM-3 inhibitor.
Subject(s)
Drug Resistance, Neoplasm , Multidrug Resistance-Associated Proteins , Multiple Myeloma , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers , Hepatitis A Virus Cellular Receptor 2/metabolism , Humans , Hydrazines , Karyopherins/genetics , Karyopherins/metabolism , Multidrug Resistance-Associated Proteins/genetics , Multiple Myeloma/drug therapy , Multiple Myeloma/genetics , Multiple Myeloma/metabolism , Neoplasm Recurrence, Local/drug therapy , Receptors, Cytoplasmic and Nuclear/metabolism , TriazolesABSTRACT
PURPOSE: Introducing an effective corrective therapy for linguoclination or buccoclination of the mandibular molars. METHODS: Using a simple semi-fixed lingual arch combined with the edgewise technology to correct 8 cases with linguoclination or buccoclination of the mandibular molars. RESULTS: Using the simple semi-fixed lingual arch can correct the malposition of mandibular molar's linguoclination or buccolination quickly and successfully. CONCLUSION: The simple semi-fixed lingual arch can fix properly the buccolingual position of the mandibular molar and can shorten the course of the fixed orthodontic therapy. In addition,this method exerts less impact on the contour of the anterior mandibular arch.
