Cheng Hao, Zhou Linxiang, Long Yalan, Xiang Juanjuan, Chen Longhua
Department of Radiation Oncology, Nanfang Hospital of Southern Medical University, Guangzhou, China.
Department of Nasopharyngeal Carcinoma, The First People's Hospital of Chenzhou, Southern Medical University, Chenzhou, China.
Front Oncol. 2021 Mar 29;11:644120. doi: 10.3389/fonc.2021.644120. eCollection 2021.
Given the reported correlation between the oncogene metastasis-associated in colon cancer 1 (MACC1) and nasopharyngeal carcinoma (NPC), as well as between MACC1 and epithelial-mesenchymal transition (EMT), we speculated that EMT is a likely causative link between MACC1 expression and poor NPC prognosis. Thus, we aim to clarify the relationship between MACC1 and EMT in NPC prognosis.
We performed immunohistochemical examination of tissue sections from 128 NPC patients that were divided into six groups corresponding to high and low protein expression of MACC1 and two EMT-related proteins, vimentin and E-cadherin, and Kaplan-Meier (KM) survival analyses were performed.
KM survival analysis showed that upregulation of MACC1 and vimentin and downregulation of E-cadherin were significantly associated with reduced survival in NPC. Short hairpin RNA (shRNA) interference and immunoblotting in the NPC cell line HNE-1 led to increased E-cadherin but decreased vimentin levels. MACC1 overexpression was significantly correlated with poor 5-year overall survival, metastasis-free survival, and disease-free survival (P<0.05) but not with poor relapse-free survival (P>0.05). Univariate analyses revealed that MACC1, E-cadherin, and vimentin levels along with T and N tumor classifications and cancer staging are significant prognostic factors of NPC (P<0.05).
Our findings showed the association between MACC1 and EMT in NPC malignancy and support the role of MACC1 as a prognostic biomarker and molecular target for NPC treatment.
鉴于已报道的结肠癌转移相关基因1（MACC1）与鼻咽癌（NPC）之间的相关性，以及MACC1与上皮-间质转化（EMT）之间的相关性，我们推测EMT可能是MACC1表达与鼻咽癌预后不良之间的因果联系。因此，我们旨在阐明MACC1与EMT在鼻咽癌预后中的关系。
我们对128例鼻咽癌患者的组织切片进行了免疫组化检查，将其分为六组，分别对应MACC1以及两种与EMT相关的蛋白波形蛋白和E-钙黏蛋白的高表达和低表达，并进行了Kaplan-Meier（KM）生存分析。
KM生存分析显示，MACC1和波形蛋白的上调以及E-钙黏蛋白的下调与鼻咽癌患者生存率降低显著相关。在鼻咽癌细胞系HNE-1中进行短发夹RNA（shRNA）干扰和免疫印迹分析，结果显示E-钙黏蛋白水平升高，但波形蛋白水平降低。MACC1过表达与5年总生存率、无转移生存率和无病生存率低显著相关（P<0.05），但与无复发生存率低无关（P>0.05）。单因素分析显示，MACC1、E-钙黏蛋白和波形蛋白水平以及T和N肿瘤分级和癌症分期是鼻咽癌的重要预后因素（P<0.05）。
我们的研究结果显示了MACC1与鼻咽癌恶性肿瘤中EMT之间的关联，并支持MACC1作为鼻咽癌治疗的预后生物标志物和分子靶点的作用。
