DKK3 as a novel biomarker for risk stratification in pediatric acute lymphoblastic leukemia

Aberrant Wnt signaling drives oncogenesis. DKK proteins, key extracellular regulators of Wnt pathway, play critical roles in tumor suppression or promotion. This study enrolled 66 newly diagnosed acute lymphoblastic leukemia (ALL) patients, stratified into low-risk (LR) and intermediate/high-risk (IR/HR) groups, alongside 39 children with immune thrombocytopenia (ITP) as controls. Bone marrow samples were collected at diagnosis and remission (day 46). DKK3 expression was measured using qRT – PCR and ELISA. Predictive performance was evaluated via ROC analysis and logistic regression. DKK3 mRNA and protein levels were significantly lower at diagnosis than in remission and control groups (<i>P</i> &lt; 0.001). LR patients showed higher DKK3 expression than IR/HR patients (<i>P</i> &lt; 0.001). ROC analysis indicated that DKK3 mRNA and protein effectively predicted IR/HR status; combined AUC reached 0.889. No significant difference was found between B-ALL and T-ALL subgroups. Low DKK3 protein was an independent risk factor for event-free survival (<i>P</i> = 0.024). DKK3 shows promise as a biomarker for early risk stratification and prognosis prediction in pediatric ALL, potentially supporting personalized treatment strategies.

异常Wnt信号通路（Wnt signaling）驱动肿瘤发生。DKK蛋白（DKK proteins）作为Wnt通路的关键细胞外调控因子，在肿瘤的发生抑制与促进过程中发挥关键作用。本研究纳入66例初诊急性淋巴细胞白血病（ALL）患者，按风险分层分为低危（LR）组与中高危（IR/HR）组，同时纳入39例免疫性血小板减少症（ITP）患儿作为对照。分别于确诊时及缓解期（第46天）采集骨髓样本。采用实时定量聚合酶链反应（qRT-PCR）与酶联免疫吸附试验（ELISA）检测DKK3的表达水平。通过受试者工作特征曲线（ROC）分析与逻辑回归（logistic regression）评估其预测性能。DKK3的mRNA与蛋白水平在确诊时显著低于缓解期及对照组（P<0.001）。低危患者的DKK3表达水平高于中高危患者（P<0.001）。受试者工作特征曲线分析显示，DKK3的mRNA与蛋白水平可有效预测中高危分层状态，联合检测的曲线下面积（AUC）可达0.889。B细胞急性淋巴细胞白血病（B-ALL）与T细胞急性淋巴细胞白血病（T-ALL）亚组间未发现显著差异。低水平DKK3蛋白是无事件生存期（event-free survival）的独立危险因素（P=0.024）。DKK3有望成为儿童ALL早期风险分层与预后预测的生物标志物，可为个性化治疗策略提供支持。