食管腺癌（OAC）的转移是生存率的重要预测指标。放射学分期用于对患者的转移进行分期，并指导治疗选择，但其准确性受到限制。分期的改进将促进临床决策和患者预后的改善。对原发肿瘤和癌前组织的测序研究揭示了OAC的突变景观，越来越便宜和普及的测序方法提供了改善分期评估的潜力。在这项工作中，我们通过放射学和病理采样的淋巴结转移进行了分析，发现了基因SMAD4和KCNQ3在转移中的新作用。通过转录组分析，我们发现这两个基因与经典Wnt通路活性相关，但KCNQ3与非经典Wnt信号调控的平面细胞极性变化相关。我们继续在细胞系和异种移植模型中验证了KCNQ3的观察结果，结果显示KCNQ3的过表达减少了伤口闭合和观察到的转移数目。我们的结果将这两个基因作为转移风险的新型生物标志物，并提供了药物靶向的新途径。版权所有©2023 Elsevier B.V.出版。

Metastasis in oesophageal adenocarcinoma (OAC) is an important predictor of survival. Radiological staging is used to stage metastases in patients, and guide treatment selection, but is limited by the accuracy of the approach. Improvements in staging will lead to improved clinical decision making and patient outcomes. Sequencing studies on primary tumours and pre-cancerous tissue have revealed the mutational landscape of OAC, and increasingly cheap and widespread sequencing approaches offer the potential to improve staging assessment. In this work we present an analysis of lymph node metastases found by radiological and pathological sampling, identifying new roles of the genes SMAD4 and KCNQ3 in metastasis. Through transcriptomic analysis we find that both genes are associated with canonical Wnt pathway activity, but KCNQ3 is uniquely associated with changes in planar cell polaritiy associated with non-canonical Wnt signalling. We go on to validate our observations in KCNQ3 in cell line and xenograph systems, showing that overexpression of KCNQ3 reduces wound closure and the number of metastases observed. Our results suggest both genes as novel biomarkers of metastatic risk and offer new potential routes to drug targeting.Copyright © 2023. Published by Elsevier B.V.