Abstract：
Colorectal cancer (CRC) and diabetes are two of the most prevalent chronic diseases worldwide with dysregulated receptor tyrosine kinase signaling and strong co-occurrence correlation. Plasma autoantibodies represent a promising early diagnostic marker for both diseases before symptoms appear. In this study, we explore the value of autoantibodies against receptor-type tyrosine-protein phosphatase-like N (PTPRN; full-length or selected domains) as diagnostic markers using a cohort of individuals with type 2 diabetes (T2D), CRC, or both diseases or healthy individuals. We show that PTPRN autoantibody levels in plasma discriminated between patients with T2D with and without CRC. Consistently, high PTPRN expression correlated with decreased survival of patients with CRC. Mechanistically, PTPRN depletion significantly reduced invasiveness of CRC cells in vitro and liver homing and metastasis in vivo by means of a dysregulation of the epithelial-mesenchymal transition and a decrease of the insulin receptor signaling pathway. Therefore, PTPRN autoantibodies may represent a particularly helpful marker for the stratification of patients with T2D at high risk of developing CRC. Consistent with the critical role played by tyrosine kinases in diabetes and tumor biology, we provide evidence that tyrosine phosphatases such as PTPRN may hold potential as therapeutic targets in patients with CRC.
摘要：
结直肠癌（CRC）和糖尿病是全球最常见的两种慢性疾病，具有受体酪氨酸激酶信号传导失调和强烈的共存相关性。在症状出现之前，血浆自身抗体代表了两种疾病的有希望的早期诊断标志物。在这项研究中,我们使用一组2型糖尿病（T2D）患者，探讨了针对受体型酪氨酸蛋白磷酸酶样N（PTPRN;全长或选定结构域）的自身抗体作为诊断标志物的价值，CRC,或两种疾病或健康个体。我们显示血浆中的PTPRN自身抗体水平可区分患有和不患有CRC的T2D患者。始终如一，PTPRN高表达与CRC患者生存率降低相关.机械上,PTPRN耗竭通过上皮-间充质转化的失调和胰岛素受体信号传导途径的减少，显着降低了CRC细胞在体外的侵袭力以及在体内的肝归巢和转移。因此,PTPRN自身抗体可能代表了一个特别有用的标记，用于对处于发生CRC高风险的T2D患者进行分层。与酪氨酸激酶在糖尿病和肿瘤生物学中所起的关键作用一致，我们提供的证据表明,PTPRN等酪氨酸磷酸酶可能作为CRC患者的治疗靶点.
