MACC1 Is Associated With Epithelial-Mesenchymal Transition and Can Predict Poor Prognosis in Nasopharyngeal Carcinoma

Hao Cheng; Linxiang Zhou; Yalan Long; Juanjuan Xiang; Longhua Chen

doi:10.3389/fonc.2021.644120

MACC1 Is Associated With Epithelial-Mesenchymal Transition and Can Predict Poor Prognosis in Nasopharyngeal Carcinoma

Front Oncol. 2021 Mar 29:11:644120. doi: 10.3389/fonc.2021.644120. eCollection 2021.

Authors

Hao Cheng^{1

2}, Linxiang Zhou³, Yalan Long³, Juanjuan Xiang³, Longhua Chen¹

Affiliations

¹ Department of Radiation Oncology, Nanfang Hospital of Southern Medical University, Guangzhou, China.
² Department of Nasopharyngeal Carcinoma, The First People's Hospital of Chenzhou, Southern Medical University, Chenzhou, China.
³ Department of Nasopharyngeal Carcinoma, The First People's Hospital of Chenzhou, University of South China, Chenzhou, China.

Abstract

Background: 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.

Material and methods: 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.

Results: 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).

Conclusion: 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.

Keywords: E-cadherin; epithelial-mesenchymal transition (EMT); metastasis-associated in colon cancer 1 (MACC1); nasopharyngeal carcinoma; prognostic biomarker; vimentin.