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血清半乳糖凝集素-9 水平可作为皮肌炎恶性肿瘤高风险的潜在生物标志物。

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

机构信息

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

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

出版信息

Rheumatology (Oxford). 2024 Jan 4;63(1):251-258. doi: 10.1093/rheumatology/kead222.

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.

摘要

目的

半乳糖凝集素-9 作为免疫检查点蛋白,在调节自身免疫和肿瘤免疫方面发挥作用。因此,我们探讨了半乳糖凝集素-9 与癌症相关糖尿病性肌病(CRDM)中恶性肿瘤之间的病理生理联系。

方法

通过酶联免疫吸附试验定量检测血清半乳糖凝集素-9,采用 Spearman 分析评估其与血清学指标的相关性。采用受试者工作特征(ROC)分析确定半乳糖凝集素-9 的截断值。

结果

糖尿病患者的血清半乳糖凝集素-9 水平明显高于健康对照组[23.38(13.85-32.57)ng/ml] [6.81(5.42-7.89)ng/ml,P<0.0001],且与皮肤肌炎疾病面积严重程度指数活动度(CDASI-A)评分呈正相关(rs=0.3065,P=0.0172)。新发和未经治疗的癌症(新 CRDM)的糖尿病患者[31.58(23.85-38.84)ng/ml]的半乳糖凝集素-9 水平高于稳定和经治疗的癌症(稳定 CRDM)[17.49(10.23-27.91)ng/ml,P=0.0288]、非癌症相关糖尿病(非 CRDM)[21.05(11.97-28.02)ng/ml,P=0.0258]和无糖尿病的肿瘤患者[7.46(4.90-8.51)ng/ml,P<0.0001]。CRDM 患者经抗癌治疗后,血清半乳糖凝集素-9水平显著下降[27.79(17.04-41.43)ng/ml比 13.88(5.15-20.37)ng/ml,P=0.002]。血清半乳糖凝集素-9与抗转录中介因子 1-γ(抗 TIF1-γ)抗体联合(AUC=0.889,95%CI 0.803-0.977)对 DM 患者癌症的存在具有最高的预测价值。

结论

CRDM 中升高的半乳糖凝集素-9 水平与肿瘤进展有关,癌症治疗后半乳糖凝集素-9水平降低。监测血清半乳糖凝集素-9水平和抗 TIF1-γ抗体可能是一种有吸引力的策略,可用于肿瘤诊断并预测 CRDM 结局。

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