Do Alarmins Have a Role in Multiple Myeloma?

Objective: Calprotectin (CLP), S100A6, and high mobility group nucleosome-binding protein 1 (HMGN1), known as alarmins, are involved in the pathogenesis of many tumors. In this study, we aimed to investigate the relationships of serum CLP, S100A6, and HMGN1 levels with the clinical and laboratory findings of patients with multiple myeloma (MM) and their roles in the pathogenesis of MM. Materials and Methods: We measured the serum CLP, S100A6, and HMGN1 levels of 55 newly diagnosed patients and 32 healthy controls using the sandwich enzyme-linked immunosorbent assay method. The medical records of the patients were also reviewed. Results: Serum CLP, S100A6, and HMGN1 levels were significantly decreased in MM patients compared to the control group (p=0.012, p=0.001, and p=0.030, respectively). Receiver operating characteristic analysis was used to determine diagnostic cut-off values for serum CLP, S100A6, and HMGN1 of <98 ng/mL (area under the curve [AUC]: 0.663, 95% confidence interval [CI]: 0.554-0.761, p=0.009), <1174.5 pg/mL (AUC: 0.706, 95% CI: 0.598-0.799, p=0.001), and <440.18 pg/mL (AUC: 0.640, 95% CI: 0.530-0.740, p=0.03), respectively. CLP levels were found to be statistically significantly higher in patients with light chain MM (91.58±22.57 ng/mL) compared to heavy chain MM (79.42±15.83 ng/mL) (p=0.03). A negative correlation was observed between CLP and M protein, immunoglobulin G, globulin, and beta-2 microglobulin (correlation coefficients: -0.361, -0.370, -0.279, -0.300, respectively; p=0.024, p=0.06, p=0.04, p=0.0033). Conclusion: In this study, we found that serum CLP, S100A6, and HMGN1 levels were statistically lower in patients with newly diagnosed MM compared to the control group. These results suggest that CLP may bind to the paraprotein produced by heavy chain MM in the blood, causing its blood levels to be low. Additionally, low levels of HMGN1, which is involved in DNA repair, suggest that HMGN1 may contribute to the complex genetic abnormalities found in cases of MM.

High-mobility group nucleosome-binding protein 1 is a novel clinical biomarker in non-small cell lung cancer.

The involvement of alarmin high-mobility group nucleosome-binding protein 1 (HMGN1) in non-small cell lung cancer (NSCLC) is unknown. To address the presence of HMGN1 in the serum of different stages of NSCLC patients and healthy controls, we enrolled a consecutive sample of adult serum at diagnosis and correlated it with clinicopathologic outcomes. A total of 100 NSCLC patients and 23 healthy volunteers were enrolled from January 2012 through December 2013. Serum HMGN1 levels were determined by enzyme-linked immunosorbent assay (ELISA). Additionally, HMGN1 levels in 50 NSCLC patients with early-stage disease who received curative pneumonectomy were correlated with survivals. Kaplan-Meier plots were used to analyze the data. The patients with NSCLC were characterized by significantly higher serum levels of HMGN1 (0.4585 ± 0.0640 ng/ml) compared to those in healthy controls (0.3578 ± 0.0304 ng/ml). The serum HMGN1 levels were 0.4027 ± 0.0271 ng/ml, 0.4604 ± 0.0328 ng/ml, 0.5408 ± 0.0459 ng/ml, and 0.4213 ± 0.0341 ng/ml in patients with TNM stages I, II, IV, and IV, respectively (p < 0.001). There were significant differences among four groups (p < 0.001). Additionally, a positive correlation between serum HMGN1 and tumor stage was found in local disease, while serum HMGN1 level in metastatic NSCLC patients was significantly decreased. The Kaplan-Meier plots showed that patients with high serum HMGN1 had a poorer overall survival (OS) after curative pneumonectomy than those with low serum HMGN1 (p = 0.019). Inflammation triggered by alarmins plays a role in NSCLC pathogenesis. HMGN1 can serve as a useful clinical parameter for evaluating disease progression and predicting the outcomes for early-stage patients with NSCLC undergoing pneumonectomy.