Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
Mol Oncol. 2018 Nov;12(11):1895-1916. doi: 10.1002/1878-0261.12356. Epub 2018 Sep 21.
Pancreatic cancer is arguably the deadliest cancer type. The efficacy of current therapies is often hindered by the inability to predict patient outcome. As such, the development of tools for early detection and risk prediction is key for improving outcome and quality of life. Here, we introduce the plasminogen receptor S100A10 as a novel predictive biomarker and a driver of pancreatic tumor growth and invasion. We demonstrated that S100A10 mRNA and protein are overexpressed in human pancreatic tumors compared to normal ducts and nonductal stroma. S100A10 mRNA and methylation status were predictive of overall survival and recurrence-free survival across multiple patient cohorts. S100A10 expression was driven by promoter methylation and the oncogene KRAS. S100A10 knockdown reduced surface plasminogen activation, invasiveness, and in vivo growth of pancreatic cancer cell lines. These findings delineate the clinical and functional contribution of S100A10 as a biomarker in pancreatic cancer.
胰腺癌可以说是最致命的癌症类型之一。目前治疗方法的疗效往往受到无法预测患者预后的限制。因此,开发早期检测和风险预测工具对于改善预后和生活质量至关重要。在这里,我们介绍纤溶酶原受体 S100A10 作为一种新的预测性生物标志物,也是胰腺肿瘤生长和侵袭的驱动因素。我们证明,与正常导管和非导管基质相比,S100A10 mRNA 和蛋白质在人类胰腺肿瘤中过度表达。S100A10 mRNA 和甲基化状态可预测多个患者队列的总生存期和无复发生存期。S100A10 的表达受启动子甲基化和致癌基因 KRAS 驱动。S100A10 敲低减少了表面纤溶酶原激活、侵袭性和胰腺癌细胞系的体内生长。这些发现描绘了 S100A10 作为胰腺癌生物标志物的临床和功能贡献。