Cancer Management and Research (Mar 2021)
High Expression of MDM2 and the p53 Protein is Predictive Biomarkers for Poor Prognosis of Oesophageal Squamous Cell Carcinoma
Abstract
Juan Ye,1,2,* Lin Zhang,2– 4,* Zhongwen Li,1 Runduan Lin,3 Yiling Song,3 Huanhe Ni,2 Xiaoxia Gou,1 Rongzhang Xie4 1Department of Head and Neck Oncology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 2Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China; 4Department of Clinical Laboratory, Yunfu People’s Hospital, Yunfu, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rongzhang Xie Tel +86 766 8861761Fax +86 766 8822491Email [email protected] Gou Tel/Fax +86 851 2759 6472Email [email protected] and Objective: In the present study, we detected the expression of MDM2 and p53 in oesophageal squamous cell carcinoma (OSCC) specimens, studied their relationship with the survival of OSCC patients, and explored the potential of MDM2 and p53 to serve as predictive OSCC tumour markers.Patients and Methods: Through immunohistochemistry and fluorescence in situ hybridization (FISH), we detected the expression of MDM2 and the p53 protein in 157 OSCC specimens that met the inclusion and exclusion criteria. After scoring the results, Pearson’s chi-square test and Cox regression were used for analysis.Results: The results showed that the rates of high MDM2 and p53 expression in OSCC tissues were 60.5% and 51.0%, respectively. The expression levels of MDM2 and p53 in OSCC were significantly positively correlated (p< 0.001, r=0.414). In addition, the pathological metastasis (M) status and MDM2 protein expression in OSCC were significantly correlated (p=0.027), and high expression of the p53 protein was positively correlated with OSCC transfer (p=0.005), pathological node status (p=0.008), and clinical stage (p=0.003). Kaplan-Meier survival analysis showed that the high expression of MDM2 and p53 was significantly related to the poor prognosis of OSCC. Moreover, subgroup analysis of the TNM staging of OSCC patients showed that the high expression of MDM2 and p53 was significantly correlated with poor OS and DFS of OSCC patients in either stage I–II or III–IV patients. Both univariate and Cox multivariate analyses showed that p53 and MDM2 can be used as independent factors for the prognosis of OSCC patients. Finally, our FISH detection results for MDM2 showed that the high expression of MDM2 was significantly correlated with the amplification of MDM2 (p=0.015).Conclusion: This study shows that MDM2 and p53 can be used as independent predictors of the prognosis of patients with oesophageal squamous cell carcinoma.Keywords: oesophageal squamous cell carcinoma, biomarkers, MDM2, p53
