Identification and validation of a platelet-related signature for predicting survival and drug sensitivity in multiple myeloma

Background: Significant progress has been achieved in the management of multiple myeloma (MM) by implementing high-dose therapy and stem cell transplantation. Moreover, the prognosis of patients has been enhanced due to the introduction of novel immunomodulatory drugs and the emergence of new targeted therapies. However, predicting the survival rates of patients with multiple myeloma is still tricky. According to recent researches, platelets have a significant impact in affecting the biological activity of tumors and are essential parts of the tumor microenvironment. Nonetheless, it is still unclear how platelet-related genes (PRGs) connect to the prognosis of multiple myeloma.Methods: We analyzed the expression of platelet-related genes and their prognostic value in multiple myeloma patients in this study. We also created a nomogram combining clinical metrics. Furthermore, we investigated disparities in the biological characteristics, immunological microenvironment, and reaction to immunotherapy, along with analyzing the drug susceptibility within diverse risk groups.Results: By using the platelet-related risk model, we were able to predict patients’ prognosis more accurately. Subjects in the high-risk cohort exhibited inferior survival outcomes, both in the training and validation datasets, as compared to those in the low-risk cohort (p < 0.05). Moreover, there were differences in the immunological microenvironments, biological processes, clinical features, and chemotherapeutic drug sensitivity between the groups at high and low risk. Using multivariable Cox regression analyses, platelet-related risk score was shown to be an independent prognostic influence in MM (p < 0.001, hazard ratio (HR) = 2.001%, 95% confidence interval (CI): 1.467–2.730). Furthermore, the capacity to predict survival was further improved when a combined nomogram was utilized. In training cohort, this outperformed the predictive value of International staging system (ISS) alone from a 5-years area under curve (AUC) = 0.668 (95% CI: 0.611–0.725) to an AUC = 0.721 (95% CI: 0.665–0.778).Conclusion: Our study revealed the potential benefits of PRGs in terms of survival prognosis of MM patients. Furthermore, we verified its potential as a drug target for MM patients. These findings open up novel possibilities for prognostic evaluation and treatment choices for MM

Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma

Background: Cuproptosis is a newly identified unique copper-triggered modality of mitochondrial cell death, distinct from known death mechanisms such as necroptosis, pyroptosis, and ferroptosis. Multiple myeloma (MM) is a hematologic neoplasm characterized by the malignant proliferation of plasma cells. In the development of MM, almost all patients undergo a relatively benign course from monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM), which further progresses to active myeloma. However, the prognostic value of cuproptosis in MM remains unknown.Method: In this study, we systematically investigated the genetic variants, expression patterns, and prognostic value of cuproptosis-related genes (CRGs) in MM. CRG scores derived from the prognostic model were used to perform the risk stratification of MM patients. We then explored their differences in clinical characteristics and immune patterns and assessed their value in prognosis prediction and treatment response. Nomograms were also developed to improve predictive accuracy and clinical applicability. Finally, we collected MM cell lines and patient samples to validate marker gene expression by quantitative real-time PCR (qRT-PCR).Results: The evolution from MGUS and SMM to MM was also accompanied by differences in the CRG expression profile. Then, a well-performing cuproptosis-related risk model was developed to predict prognosis in MM and was validated in two external cohorts. The high-risk group exhibited higher clinical risk indicators. Cox regression analyses showed that the model was an independent prognostic predictor in MM. Patients in the high-risk group had significantly lower survival rates than those in the low-risk group (p < 0.001). Meanwhile, CRG scores were significantly correlated with immune infiltration, stemness index and immunotherapy sensitivity. We further revealed the close association between CRG scores and mitochondrial metabolism. Subsequently, the prediction nomogram showed good predictive power and calibration. Finally, the prognostic CRGs were further validated by qRT-PCR in vitro.Conclusion: CRGs were closely related to the immune pattern and self-renewal biology of cancer cells in MM. This prognostic model provided a new perspective for the risk stratification and treatment response prediction of MM patients

Prognostic significance of β2-microglobulin decline index in multiple myeloma

PurposeTo assess the prognostic significance of β2-microglobulin decline index (β2M DI) in multiple myeloma (MM).Methods150 MM patients diagnosed with MM were enrolled in this study. Cox proportional hazards model was used to analyze the uni- and multivariate prognosis in training cohort (n=105). A new combined prognostic model containing β2M DI was built up based on the data in training cohort. The validation group was used to verify the model.Resultsβ2M DI showed significant correlation with prognosis in both uni- and multivariate analyses and had a good correlation with complete response (CR) rate and deep remission rate. The ROC and calibration curves in validation cohort (n=45) indicated a good predictive performance of the new model. Based on the median risk score of the training group, we classified patients into high- and low- risk groups. In both training and validation groups, patients in the low-risk group had longer overall survival (OS) time than that in the high-risk group (p<0.05).Conclusionβ2M DI is a good predictive index for predicting treatment response and survival time in MM patients. The prognostic model added with β2M DI showed a better correlation with OS

A novel glycolysis-related gene signature for predicting the prognosis of multiple myeloma

Background: Metabolic reprogramming is an important hallmark of cancer. Glycolysis provides the conditions on which multiple myeloma (MM) thrives. Due to MM’s great heterogeneity and incurability, risk assessment and treatment choices are still difficult.Method: We constructed a glycolysis-related prognostic model by Least absolute shrinkage and selection operator (LASSO) Cox regression analysis. It was validated in two independent external cohorts, cell lines, and our clinical specimens. The model was also explored for its biological properties, immune microenvironment, and therapeutic response including immunotherapy. Finally, multiple metrics were combined to construct a nomogram to assist in personalized prediction of survival outcomes.Results: A wide range of variants and heterogeneous expression profiles of glycolysis-related genes were observed in MM. The prognostic model behaved well in differentiating between populations with various prognoses and proved to be an independent prognostic factor. This prognostic signature closely coordinated with multiple malignant features such as high-risk clinical features, immune dysfunction, stem cell-like features, cancer-related pathways, which was associated with the survival outcomes of MM. In terms of treatment, the high-risk group showed resistance to conventional drugs such as bortezomib, doxorubicin and immunotherapy. The joint scores generated by the nomogram showed higher clinical benefit than other clinical indicators. The in vitro experiments with cell lines and clinical subjects further provided convincing evidence for our study.Conclusion: We developed and validated the utility of the MM glycolysis-related prognostic model, which provides a new direction for prognosis assessment, treatment options for MM patients

Load Forecast of Electric Vehicle Charging Station Considering Multi-Source Information and User Decision Modification

In view of the current multi-source information scenario, this paper proposes a decision-making method for electric vehicle charging stations (EVCSs) based on prospect theory, which considers payment cost, time cost, and route factors, and is used for electric vehicle (EV) owners to make decisions when the vehicle’s electricity is low. Combined with the multi-source information architecture composed of an information layer, algorithm layer, and model layer, the load of EVCSs in the region is forecast. In this paper, the Monte Carlo method is used to test the IEEE-30 model and the traffic network based on it, and the spatial and temporal distribution of charging load in the region is obtained, which verifies the effectiveness of the proposed method. The results show that EVCS load forecasting based on the prospect theory under the influence of multi-source information will have an impact on the space–time distribution of the EVCS load, which is more consistent with the decisions of EV owners in reality

Load Forecast of Electric Vehicle Charging Station Considering Multi-Source Information and User Decision Modification

In view of the current multi-source information scenario, this paper proposes a decision-making method for electric vehicle charging stations (EVCSs) based on prospect theory, which considers payment cost, time cost, and route factors, and is used for electric vehicle (EV) owners to make decisions when the vehicle’s electricity is low. Combined with the multi-source information architecture composed of an information layer, algorithm layer, and model layer, the load of EVCSs in the region is forecast. In this paper, the Monte Carlo method is used to test the IEEE-30 model and the traffic network based on it, and the spatial and temporal distribution of charging load in the region is obtained, which verifies the effectiveness of the proposed method. The results show that EVCS load forecasting based on the prospect theory under the influence of multi-source information will have an impact on the space–time distribution of the EVCS load, which is more consistent with the decisions of EV owners in reality

Halogenated Thermally Activated Delayed Fluorescence Materials for Efficient Scintillation

Organic scintillators, materials with the ability to exhibit luminescence when exposed to X-rays, have aroused increasing interest in recent years. However, the enhancement of radioluminescence and improving X-ray absorption of organic scintillators lie in the inherent dilemma, due to the waste of triplet excitons and weak X-ray absorption during scintillation. Here, we employ halogenated thermally activated delayed fluorescence materials to improve the triplet exciton utilization and X-ray absorption simultaneously, generating efficient scintillation with a low detection limit, which is one order of magnitude lower than the dosage for X-ray medical diagnostics. Through experimental study and theoretical calculation, we reveal the positive role of X-ray absorption, quantum yields of prompt fluorescence, and intersystem crossing in promoting the radioluminescence intensity. This finding offers an opportunity to design diverse types of organic scintillators and expands the applications of thermally activated delayed fluorescence

Image1_Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma.JPEG

Background: Cuproptosis is a newly identified unique copper-triggered modality of mitochondrial cell death, distinct from known death mechanisms such as necroptosis, pyroptosis, and ferroptosis. Multiple myeloma (MM) is a hematologic neoplasm characterized by the malignant proliferation of plasma cells. In the development of MM, almost all patients undergo a relatively benign course from monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM), which further progresses to active myeloma. However, the prognostic value of cuproptosis in MM remains unknown.Method: In this study, we systematically investigated the genetic variants, expression patterns, and prognostic value of cuproptosis-related genes (CRGs) in MM. CRG scores derived from the prognostic model were used to perform the risk stratification of MM patients. We then explored their differences in clinical characteristics and immune patterns and assessed their value in prognosis prediction and treatment response. Nomograms were also developed to improve predictive accuracy and clinical applicability. Finally, we collected MM cell lines and patient samples to validate marker gene expression by quantitative real-time PCR (qRT-PCR).Results: The evolution from MGUS and SMM to MM was also accompanied by differences in the CRG expression profile. Then, a well-performing cuproptosis-related risk model was developed to predict prognosis in MM and was validated in two external cohorts. The high-risk group exhibited higher clinical risk indicators. Cox regression analyses showed that the model was an independent prognostic predictor in MM. Patients in the high-risk group had significantly lower survival rates than those in the low-risk group (p Conclusion: CRGs were closely related to the immune pattern and self-renewal biology of cancer cells in MM. This prognostic model provided a new perspective for the risk stratification and treatment response prediction of MM patients.</p