Low Expression of DYRK2 (Dual Specificity Tyrosine Phosphorylation Regulated Kinase 2) Correlates with Poor Prognosis in Colorectal Cancer.
Low Expression of DYRK2 (Dual Specificity Tyrosine Phosphorylation Regulated Kinase 2) Correlates with Poor Prognosis in Colorectal Cancer.
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DYRK2（双特异性酪氨酸磷酸化调节激酶 2）的低表达与结直肠癌的不良预后相关
DOI：
10.1371/journal.pone.0159954
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yin D
中科院分区：
文献类型：
--
作者：
Yan H;Hu K;Wu W;Li Y;Tian H;Chu Z;Koeffler HP;Yin D
双特异性酪氨酸磷酸化调节激酶 2 (DYRK2) 是双特异性激酶家族的一员，可以磷酸化 Ser/Thr 和 Tyr 底物。 DYRK2 在人类癌症中的作用仍存在争议。例如，DYRK2 的过度表达可预测人类非小细胞肺癌的更好生存率。相反，DYRK2 基因的扩增发生在食管/肺腺癌中，这意味着 DYRK2 作为潜在癌基因的作用。然而，其在结直肠癌（CRC）中的临床作用尚未被探索。在本研究中，我们分析了 Oncomine 数据库中 DYRK2 的表达，发现在 6 个结直肠癌数据集中，原发性或转移性 CRC 中的 DYRK2 水平分别低于邻近正常结肠组织或非转移性 CRC。还通过实时 PCR 和 IHC 研究了 181 名 CRC 患者中 DYRK2 表达与临床结果之间的相关性。与癌旁非肿瘤组织相比，结直肠癌组织中 DYRK2 的表达显着下调。功能研究证实，DYRK2 抑制 HCT116 和 SW480 细胞中的细胞侵袭和迁移，并在 CRC 细胞中发挥抑癌作用。此外，较低的 DYRK2 水平与肿瘤部位 (P = 0.023)、晚期临床分期 (P = 0.006) 和晚期临床分期的较短生存期相关。单变量和多变量分析表明DYRK2表达是一个独立的预后因素（P < 0.001）。综上所述，我们得出结论，DYRK2 是人类结直肠癌的一种新型预后生物标志物。
Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) is a member of dual-specificity kinase family, which could phosphorylate both Ser/Thr and Tyr substrates. The role of DYRK2 in human cancer remains controversial. For example, overexpression of DYRK2 predicts a better survival in human non-small cell lung cancer. In contrast, amplification of DYRK2 gene occurs in esophageal/lung adenocarcinoma, implying the role of DYRK2 as a potential oncogene. However, its clinical role in colorectal cancer (CRC) has not been explored. In this study, we analyzed the expression of DYRK2 from Oncomine database and found that DYRK2 level is lower in primary or metastatic CRC compared to adjacent normal colon tissue or non-metastatic CRC, respectively, in 6 colorectal carcinoma data sets. The correlation between DYRK2 expression and clinical outcome in 181 CRC patients was also investigated by real-time PCR and IHC. DYRK2 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues. Functional studies confirmed that DYRK2 inhibited cell invasion and migration in both HCT116 and SW480 cells and functioned as a tumor suppressor in CRC cells. Furthermore, the lower DYRK2 levels were correlated with tumor sites (P = 0.023), advanced clinical stages (P = 0.006) and shorter survival in the advanced clinical stages. Univariate and multivariate analyses indicated that DYRK2 expression was an independent prognostic factor (P < 0.001). Taking all, we concluded that DYRK2 a novel prognostic biomarker of human colorectal cancer.