Abstract: 【Abstract】 Objective To investigate the clinical significance of serum galectin-9 （Gal-9） in patients with dermatomyositis （DM） or clinically amyopathic dermatomyositis （CADM）. Methods This cross-sectional study included 105 newly diagnosed patients with DM or CADM who were admitted to the Department of Dermatology in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from January 2015 to October 2024, among whom 53 had cancer-associated DM/CADM （CRDM）. Additionally, an age-matched control group was included, consisting of 30 newly diagnosed cancer patients without autoimmune diseases, 27 systemic lupus erythematosus （SLE） patients, and 31 healthy controls. Serum levels of Gal-9 and transcriptional intermediary factor 1-gamma （TIF1-γ） were measured using enzyme-linked immunosorbent assay. The relationship between Gal-9 levels and laboratory indicators of DM disease activity was analyzed. Comparisons between different groups were performed using the t-test, Mann-Whitney U test, and chi-square test. Spearman correlation analysis was used to assess the association between Gal-9 levels and laboratory indicators. The diagnostic efficacy of Gal-9 and TIF1-γ for CRDM was evaluated using receiver operating characteristic （ROC） curve analysis. Results Among the 105 DM/CADM patients, 35 were male （33.3%） and 70 were female （66.7%）, with a mean age of 53.2 ± 15.1 years. In the 53 CRDM patients, the incidence rates of V-neck sign, dyschromia, and dysphagia were higher than those in non-CRDM patients （all P > 0.05）. Serum Gal-9 levels in DM/CADM patients （21.2 ［12.2, 32.3］ ng/ml） were significantly higher than those in healthy controls （6.8 ［5.4, 7.9］ ng/ml, P < 0.001）, SLE patients （12.3 ［8.1, 15.5］ ng/ml, P = 0.011）, and cancer patients without autoimmune diseases （7.5 ［4.9, 8.5］ ng/ml, P < 0.001）. Gal-9 levels were positively correlated with serum TIF1-γ antibody levels （rs = 0.21, P = 0.029）, serum ferritin （rs = 0.29, P = 0.003）, lactate dehydrogenase （rs = 0.44, P < 0.001）, creatine kinase （rs = 0.28, P = 0.004）, aspartate aminotransferase （rs = 0.42, P < 0.001）, C-reactive protein （rs = 0.34, P < 0.001）, and erythrocyte sedimentation rate （rs = 0.46, P < 0.001）. Among CRDM patients, those who had not received cancer treatment had higher Gal-9 levels （30.1 ［23.3, 38.3］ ng/ml） than those in stable condition after cancer treatment （13.5 ［10.5, 27.9］ ng/ml, P = 0.007）. The area under the ROC curve （AUC） for serum TIF1-γ in diagnosing CRDM was 0.718, with an optimal cutoff value of 23.02 U/ml. The AUC for serum Gal-9 was 0.719, with an optimal cutoff value of 55.02 ng/ml. When combining both markers, the AUC increased to 0.783, with a sensitivity of 0.85 and specificity of 0.74. Conclusions Gal-9 was highly expressed in serum of DM/CADM patients, particularly in CRDM patients. Dynamic monitoring of Gal-9 in CRDM patients may be helpful to monitor the therapeutic effect of malignancies.

Key words: Dermatomyositis, Galectins, Neoplasms, Autoimmune diseases, Biomarkers, Myositis-specific autoantibodies