Department of ENT, The Affiliated Hospital of Qingdao University, Qingdao Municipal Hospital, Qingdao, P.R. China.
Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao Municipal Hospital, Qingdao, P.R. China.
Cancer Biother Radiopharm. 2019 Sep;34(7):436-443. doi: 10.1089/cbr.2019.2771. Epub 2019 Apr 25.
The Wnt/β-catenin signaling pathway is one of the highly conserved signaling pathway widely reported to play essential roles in the development of various tumors and human cancers, thus serving as a potential target for anticancer therapy. However, the specific effects of the related proteins in the Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma (NPC) still remain elusive. Thus, this study was performed to uncover the correlation between the Wnt/β-catenin signaling pathway-related proteins and the clinical characteristics and prognosis of NPC. NPC tissues were revealed to present high expression of β-catenin and v-myc myelocytomatosis viral oncogene homolog (c-MYC) but low expression of Dickkopf-3 (DKK-3). Immunohistochemical staining revealed that DKK-3 was positively linked to but β-catenin and c-MYC were negatively linked to differentiation, tumor-node-metastasis (TNM) stage and lymph node metastasis of patients with NPC. In addition, c-MYC was identified to be positively correlated to DKK-3 in NPC tissues. The positive expression of β-catenin and c-MYC had negative relations with and that of DKK-3 had positive relations with survival rate of patients with NPC, which was analyzed by Kaplan-Meier method. Moreover, it was shown that later TNM stage and positive expression of β-catenin were risk factors for NPC-related death. These findings provide evidence that the proteins related to the Wnt/β-catenin signaling pathway (DKK-3, β-catenin, and c-MYC) participate in the development of NPC and positive expression of DKK-3 and negative expression of β-catenin, and c-MYC can serve as essential prognostic biomarkers, shedding new light on the prognosis and treatment of NPC.
Wnt/β-catenin 信号通路是高度保守的信号通路之一，广泛报道其在各种肿瘤和人类癌症的发生发展中发挥重要作用，因此成为抗癌治疗的潜在靶点。然而，Wnt/β-catenin 信号通路相关蛋白在鼻咽癌（NPC）中的具体作用仍不清楚。因此，本研究旨在揭示 Wnt/β-catenin 信号通路相关蛋白与 NPC 临床特征和预后的相关性。研究结果表明，NPC 组织中β-catenin 和 v-myc 髓细胞瘤病毒癌基因同源物（c-MYC）表达较高，Dickkopf-3（DKK-3）表达较低。免疫组织化学染色显示，DKK-3 与 NPC 患者的分化、肿瘤-淋巴结-转移（TNM）分期和淋巴结转移呈正相关，但与β-catenin 和 c-MYC 呈负相关。此外，还发现 NPC 组织中 c-MYC 与 DKK-3 呈正相关。Kaplan-Meier 分析显示，β-catenin 和 c-MYC 的阳性表达与 NPC 患者的生存率呈负相关，而 DKK-3 的阳性表达与 NPC 患者的生存率呈正相关。此外，TNM 分期较晚和β-catenin 阳性表达是 NPC 相关死亡的危险因素。这些发现为 Wnt/β-catenin 信号通路相关蛋白（DKK-3、β-catenin 和 c-MYC）参与 NPC 的发生发展提供了证据，DKK-3 的阳性表达和β-catenin、c-MYC 的阴性表达可作为重要的预后生物标志物，为 NPC 的预后和治疗提供了新的思路。
