High Expression of MDM2 and the p53 Protein is Predictive Biomarkers for Poor Prognosis of Oesophageal Squamous Cell Carcinoma

Abstract

Background 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

Acknowledgments

We thank the staff of the biochemical lab of Sun Yat-sen University Cancer Center who provided various biochemical markers and all the staff who supported our study.

Author Contributions

JY and LZ contributed equally. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.