外周血Tim-3、Galectin-9、LAG-3表达与多发性骨髓瘤患者化疗反应及预后的关系分析-东南大学学报医学版

外周血Tim-3、Galectin-9、LAG-3表达与多发性骨髓瘤患者化疗反应及预后的关系分析

单位：1. 重庆医科大学附属永川医院血液内科, 重庆 402160;
2. 重庆医科大学附属永川医院检验科, 重庆 402160

关键词：多发性骨髓瘤化疗反应预后 T细胞免疫球蛋白及黏蛋白-3 半乳糖凝集素-9 淋巴细胞活化基因-3

分类号：R733.33

出版年·卷·期（页码）：2025·44·第四期（556-562）

摘要：

目的:探讨外周血T细胞免疫球蛋白及黏蛋白-3(Tim-3)、半乳糖凝集素-9(Galectin-9)、淋巴细胞活化基因-3(LAG-3)表达与多发性骨髓瘤(MM)患者化疗反应及预后的关系。方法:选取2019年3月至2022年3月本院收治的109例MM患者,所有患者接受VD/PAD方案化疗4个疗程,化疗前检测外周血Tim-3⁺CD4⁺T细胞占比、LAG-3⁺CD4⁺T细胞占比以及Galectin-9水平,化疗后采用国际骨髓瘤工作组(IMWG)标准评估反应性并依此将患者分为抵抗组和敏感组。所有患者出院随访24个月,Kaplan-Meier法绘制MM患者生存曲线,多因素Cox风险比例回归分析影响MM患者预后的因素。结果:化疗结束后抵抗45例,敏感64例。抵抗组外周血Tim-3⁺CD4⁺T细胞占比、LAG-3⁺CD4⁺T细胞占比以及Galectin-9水平均高于敏感组(P＜0.05)。随访期间失访2例,死亡32例,存活75例。高Tim-3⁺CD4⁺T细胞占比组、高LAG-3⁺CD4⁺T细胞占比组、高水平Galectin-9组MM患者总生存率低于低Tim-3⁺CD4⁺T细胞占比组、低LAG-3⁺CD4⁺T细胞占比组、低水平Galectin-9组MM患者(P＜0.05)。死亡组外周血Tim-3⁺CD4⁺T细胞占比、LAG-3⁺CD4⁺T细胞占比以及Galectin-9水平均高于存活组(P＜0.05)。多因素Cox风险比例回归结果显示,化疗抵抗、高Tim-3⁺CD4⁺T细胞占比、高LAG-3⁺CD4⁺T细胞占比、高水平Galectin-9是MM患者随访期间死亡的危险因素(P＜0.05)。结论:MM患者外周血中Tim-3⁺CD4⁺T细胞占比、LAG-3⁺CD4⁺T细胞占比、Galectin-9水平增高与化疗抵抗以及不良预后有关。

Objective: To investigate the association between peripheral blood T-cell immunoglobulin and mucin domain-3(TIM-3), lymphocyte activation gene-3(LAG-3), and Galectin-9 expression levels and their predictive value for chemotherapy response and prognosis in patients with multiple myeloma(MM). Methods: A total of 109 newly diagnosed MM patients admitted to our hospital between March 2019 and March 2022 were enrolled. All patients received 4 cycles of VD/PAD regimen chemotherapy. Pre-chemotherapy peripheral blood samples were analyzed for TIM-3⁺CD4⁺ T cells, LAG-3⁺CD4⁺ T cells, and serum Galectin-9 levels using flow cytometry and ELISA. Chemotherapy response was evaluated according to the International Myeloma Working Group(IMWG) criteria, categorizing patients into resistant(n=45) and sensitive(n=64) groups. All patients were followed for 24 months post-treatment. Kaplan-Meier survival analysis and Cox proportional hazards regression were performed to assess prognostic factors. Results: The resistant group exhibited significantly higher proportions of TIM-3⁺CD4⁺ T cells, LAG-3⁺CD4⁺ T cells, and serum Galectin-9 levels compared to the sensitive group(P<0.05). During follow-up, 32 patients died, and 75 survived(2 lost). Patients with high TIM-3⁺CD4⁺ T cells, high LAG-3⁺CD4⁺ T cells, or elevated Galectin-9 demonstrated significantly worse overall survival(OS) than those with low levels(P<0.05). Deceased patients had higher baseline TIM-3⁺CD4⁺ T cells, LAG-3⁺CD4⁺ T cells, and Galectin-9 levels compared to survivors(P<0.05). Multivariate Cox analysis identified chemotherapy resistance, elevated TIM-3⁺CD4⁺ T cells, LAG-3⁺CD4⁺ T cells, and Galectin-9 levels as independent risk factors for mortality(P<0.05). Conclusion: Elevated peripheral blood TIM-3⁺CD4⁺ T cells, LAG-3⁺CD4⁺ T cells, and Galectin-9 levels are strongly associated with chemotherapy resistance and poor prognosis in MM patients, suggesting their potential as biomarkers for risk stratification and therapeutic targets.

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