Serum level of galectin-9 as a potential biomarker for high risk of malignancy in dermatomyositis

Author:

Shih Yanting1ORCID,Chen Shile1ORCID,Huang Jie2ORCID,Chen Yongheng1ORCID,Zhu Zicong1ORCID,Zhao Qian1ORCID,Zhao Xiaoqing1ORCID,Xue Feng1ORCID,Xiang Jie3ORCID,Chen Xiaosong4ORCID,Zhu Xuemei5ORCID,Pan Meng1ORCID,Wu Jun6ORCID,Zheng Jie1ORCID,Li Hao7ORCID,Cao Hua1ORCID

Affiliation:

1. Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China

2. Department of Dermatology, Wuxi Branch of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China

3. Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China

4. Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China

5. Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China

6. Shanghai Institute for Biomedical and Pharmaceutical Technologies , Shanghai, China

7. Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China

Abstract

Abstract Objectives Galectin-9, as immune checkpoint protein, plays a role in regulating autoimmunity and tumour immunity. Therefore, we explored the pathophysiological link between galectin-9 and malignancy in cancer-related DM (CRDM). Methods Serum galectin-9 were quantified via enzyme-linked immunosorbent assay, and its association with serological indices was evaluated using Spearman analysis. Receiver operating characteristic (ROC) analysis was utilized to determine the cut-off value of galectin-9. Results Serum levels of galectin-9 were significantly higher in DM patients [23.38 (13.85–32.57) ng/ml] than those in healthy controls (HCs) [6.81 (5.42–7.89) ng/ml, P < 0.0001], and were positively correlated with the cutaneous dermatomyositis disease area severity index activity (CDASI-A) scores (rs=0.3065, P = 0.0172). DM patients with new-onset and untreated cancer (new-CRDM) [31.58 (23.85–38.84) ng/ml] had higher levels of galectin-9 than those with stable and treated cancer (stable-CRDM) [17.49 (10.23–27.91) ng/ml, P = 0.0288], non-cancer-related DM (non-CRDM) [21.05 (11.97–28.02) ng/ml, P = 0.0258], and tumour patients without DM [7.46 (4.90–8.51) ng/ml, P < 0.0001]. Serum galectin-9 levels significantly decreased [27.79 (17.04–41.43) ng/ml vs 13.88 (5.15–20.37) ng/ml, P = 0.002] after anti-cancer treatment in CRDM patients. The combination of serum galectin-9 and anti-transcriptional intermediary factor 1-γ (anti-TIF1-γ) antibody (AUC = 0.889, 95% CI 0.803–0.977) showed the highest predictive value for the presence of cancer in DM. Conclusion Increased galectin-9 levels were related to tumor progression in CRDM, and galectin-9 was downregulated upon cancer treatment. Monitoring serum galectin-9 levels and anti-TIF1-γ antibodies might be an attractive strategy to achieve tumour diagnosis and predict CRDM outcome.

Funder

National Natural Science Foundation of China

Clinical Research Plan of SHDC

National Key Clinical Specialty

Shanghai Municipal Education Commission–Gaofeng Clinical Medicine Grant

Science and Technology Commission of Shanghai Municipality

Shanghai Yiyuan Rising Star Outstanding Young Medical Talents

Innovative Research Team of High-level Local Universities in Shanghai

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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