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Multiple myeloma (MM) is an incurable plasma cell malignancy accounting for approximately 10% of hematological malignancies. Identification of reliable biomarkers for better diagnosis and prognosis remains a major challenge. This study aimed to identify potential serum prognostic biomarkers corresponding to MM disease activity and evaluate their impact on patient outcomes. Serum proteomic profiles of patients with MM and age-matched controls were performed using LC–MS/MS. In the verification and validation phases, the concentration of the candidate biomarkers was measured using an ELISA technique. In addition, the association of the proposed biomarkers with clinical outcomes was assessed. We identified 23 upregulated and 15 downregulated proteins differentially expressed in newly diagnosed and relapsed/refractory MM patients compared with MM patients who achieved at least a very good partial response to treatment (≥VGPR). The top two candidate proteins, metastasis-associated protein-2 (MTA2) and argonaute-2 (AGO2), were selected for further verification and validation studies. Both MTA2 and AGO2 showed significantly higher levels in the disease-active states than in the remission states (p < 0.001). Regardless of the patient treatment profile, high MTA2 levels were associated with shorter progression-free survival (p = 0.044; HR = 2.48; 95% CI, 1.02 to 6.02). Conversely, high AGO2 levels were associated with IgG and kappa light-chains isotypes and an occurrence of bone involvement features (p < 0.05) and were associated with prolonged time to response (p = 0.045; HR = 3.00; 95% CI, 1.03 to 8.76). Moreover, the analytic results using a publicly available NCBI GEO dataset revealed that AGO2 overexpression was associated with shorter overall survival among patients with MM (p = 0.032, HR = 1.60, 95% CI, 1.04 to 2.46). In conclusion, MTA2 and AGO2 proteins were first identified as potential biomarkers that reflect disease activity, provide prognostic values and could serve as non-invasive indicators for disease monitoring and outcome predicting among patients with MM.

Background: Multiple myeloma (MM) is an incurable plasma cell malignancy. Several studies have demonstrated usefulness of the proteomic approach to identify potential biomarkers in various malignancies; however, data in patients with MM are limited. Identifying novel biomarkers that can reliably indicate disease activity, progression and patient outcomes remains a major challenge. This study aimed to identify potential prognostic biomarkers corresponding to MM disease activity and evaluate their impact on patient outcomes.Methods: Serum proteomic profiles of patients and age-matched controls were analyzed. The expression of the candidate proteins was confirmed using an NCBI Gene Expression Omnibus dataset. In the verification and validation phases, the concentration of the candidate biomarkers was measured using an enzyme-linked immunosorbent assay. In addition, the association of the proposed biomarkers with clinical outcomes was assessed.Results: Focused on newly diagnosed MM and relapsed/refractory MM, 23 upregulated and 15 downregulated proteins were identified. The top two proteins, metastasis-associated protein-2 (MTA2) and argonaute-2 (AGO2), were selected for further verification and validation studies as candidate biomarkers. We found that both MTA2 and AGO2 showed significantly higher levels in the disease active states compared with the remission states (p < 0.001). Regardless of the patient treatment profile, high MTA2 levels were associated with shorter progression-free survival (PFS, p = 0.008, HR = 2.16, 95% CI: 1.01-5.11). Conversely, high AGO2 levels were associated with IgG and kappa light-chains isotypes and bone involvement features (p < 0.05), and associated with prolonged time to response (TTR, p = 0.046, HR = 2.92, 95% CI: 1.02-8.40) among patients with MM.Conclusion: MTA2 and AGO2 proteins were firstly identified as potential serum biomarkers providing diagnostic and prognostic values. Elevated levels of those biomarkers were associated with adverse outcomes in patients with MM. Implementing serum MTA2 and AGO2 may be beneficial due to its simplicity, shortening turn-around time, being less painful, and able to perform in a routine laboratory.

Background The high concentrated thrombin time (hcTT), a thrombin time modified by increasing the thrombin concentration, is a possible alternative assay to activated partial thromboplastin time (aPTT) in unfractionated heparin (UFH) monitoring. This study aimed to determine the optimal thrombin concentration used in the hcTT assay for UFH monitoring. Methods A total of 30 blood samples obtained from healthy volunteers were included in this study. Thrombin concentrations of 10.0, 15.0, 20.0, and 25.0 IU/ml were used in the hcTT assay. The consistency between the hcTT and anti‐FXa assays was evaluated. To validate the hcTT assay, linearity, repeatability, reproducibility, and diagnostic performance of the assay were assessed. Results The hcTT assay using thrombin concentration of 15.0 IU/ml showed a strong correlation to the anti‐FXa assay with R2 of 0.72 and the Spearman's correlation coefficient (rs) of 0.97 (95% CI, 0.96–0.98). Within‐run and day‐to‐day run variabilities of the assay were satisfactory (all coefficients of variation <10%). We found an excellent correlation between the results which were measured using different reagents with intra‐ or inter‐laboratory instruments. Notably, as compared to the aPTT assay, the hcTT assay showed a significantly better performance in identifying the samples which contain UFH at the supratherapeutic level, with an AUC of 0.97 vs. 0.91, p = 0.049. Conclusion The hcTT assay can be used as an alternative assay for UFH therapy monitoring. A further study using clinical samples is recommended to confirm the appropriateness of the hcTT assay for clinical application.

Background: Female adolescents aged 10 to 19 years are at remarkable risk of iron deficiency anemia (IDA). Reticulocyte hemoglobin equivalent (Ret-He) is an initial indicator of iron incorporation in red blood cells (RBCs) hemoglobin and reflects the iron functional availability in the RBCs. Objective: This study aimed to assess the diagnostic performance of Ret-He to identify IDA and determine a specific cut-off value for Thai female adolescents. Methods: Blood samples of 191 Thai female adolescents, ages ranging from 12 to 18 years, were included. Patients underwent complete blood count, reticulocyte count, Ret-He, serum iron (SI), total iron-binding capacity (TIBC), and transferrin saturation (TSAT). The correlation of Ret-He with other parameters and the diagnostic performance to identify IDA were evaluated. Results: Among 191 patients, 89 and 102 were defined as IDA and non-IDA groups. Ret-He value in the IDA group was significantly lower than that in the non-IDA group (p<0.001). Strong positive correlations were observed between Ret-He and RBC indices and SI and TSAT (p<0.001). A Ret-He value of ≤27.0 pg could distinguish IDA from non-IDA with a sensitivity of 91.2% and a specificity of 100.0% (area under the curve, AUC of 0.99, 95% CI: 0.98-0.99; p<0.001). Conclusion: This study confirmed that Ret-He is a cost-effective parameter representing an advantage over other traditional iron markers. A specific Ret-He cut-off value of ≤27.0 pg is suitable for distinguishing IDA from non-IDA with excellent diagnostic performance among Thai female adolescents.