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基线瘤基因表达特征与犬B细胞淋巴瘤中化疗免疫治疗反应相关

Katherine Dittrich¹, Ümmügülsüm Yıldız-Altay², Fatima Qutab²

¹Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, United States of America.

|August 25, 2023

概括

识别基因表达生物标志物可以预测患有扩散大B细胞淋巴瘤 (DLBCL) 的狗的治疗反应. 这项研究有助于个性化犬癌症治疗,并为人类临床试验提供信息.

科学领域:

兽医瘤学兽医瘤学
比较瘤学的比较.
分子生物学分子生物学

背景情况:

物狗的自发扩散大B细胞淋巴瘤 (DLBCL) 为人类DLBCL研究提供了有价值的模型.
选择犬类DLBCL的最佳治疗方法仍然是一个挑战,影响患者的治疗结果.

研究的目的:

确定基线基因表达差异,预测DLBCL.狗的治疗反应.
探索潜在的生物标志物,以指导犬类DLBCL中的化疗免疫治疗选择.

主要方法:

从使用NanoString nCounter犬免疫瘤学 (IO) 面板的18只DLBCL受影响的狗中吸收的淋巴结的基因表达特征.
基因表达的差异分析在基线良好反应者 (复发>90天) 和不良反应者 (复发<90天) 之间的基因表达差异.
使用定量PCR (qPCR) 验证候选生物标志物基因趋势.

主要成果:

增加的CCND3表达与预后不佳相关,而增加的CD36与预后良好相关,反映了人类DLBCL发现.
不同的基因表达模式与对特定治疗的反应有关:KPT-9274 (CREBBP,CDKN1A),TAK-981 (TLR3) 和RV1001 (PI3Kδ,AKT3,PTEN,NRAS).
在治疗手臂中差异表达基因的最小重叠凸显了对队列特定分析的需求.

结论:

狗DLBCL表现出显著的异质性,与人类DLBCL相比,具有显著的相似性和差异.
已识别的基线基因表达生物标志物可能有助于针对个体狗的化学免疫疗法治疗选择.
这项研究推进了兽医瘤学中的个性化医学方法,并为人类比较瘤学提供了洞察力.

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