MDM2和p53蛋白的高表达是食管鳞状细胞癌预后不良的预测生物标志物。
High Expression of MDM2 and the p53 Protein is Predictive Biomarkers for Poor Prognosis of Oesophageal Squamous Cell Carcinoma.
作者信息
Ye Juan, Zhang Lin, Li Zhongwen, Lin Runduan, Song Yiling, Ni Huanhe, Gou Xiaoxia, Xie Rongzhang
机构信息
Department of Head and Neck Oncology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People's Republic of China.
Department 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.
出版信息
Cancer Manag Res. 2021 Mar 23;13:2733-2744. doi: 10.2147/CMAR.S280326. eCollection 2021.
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 (<0.001, r=0.414). In addition, the pathological metastasis (M) status and MDM2 protein expression in OSCC were significantly correlated (=0.027), and high expression of the p53 protein was positively correlated with OSCC transfer (=0.005), pathological node status (=0.008), and clinical stage (=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 (=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.
背景与目的
在本研究中，我们检测了食管鳞状细胞癌（OSCC）标本中MDM2和p53的表达，研究它们与OSCC患者生存率的关系，并探讨MDM2和p53作为OSCC肿瘤预测标志物的潜力。
患者与方法
通过免疫组织化学和荧光原位杂交（FISH），我们检测了157例符合纳入和排除标准的OSCC标本中MDM2和p53蛋白的表达。对结果进行评分后，采用Pearson卡方检验和Cox回归进行分析。
结果
结果显示，OSCC组织中MDM2和p53高表达率分别为60.5%和51.0%。OSCC中MDM2和p53的表达水平呈显著正相关（<0.001，r = 0.414）。此外，OSCC的病理转移（M）状态与MDM2蛋白表达显著相关（= 0.027），p53蛋白高表达与OSCC转移（= 0.005）、病理淋巴结状态（= 0.008）及临床分期（= 0.003）呈正相关。Kaplan-Meier生存分析显示，MDM2和p53高表达与OSCC预后不良显著相关。此外，OSCC患者TNM分期的亚组分析显示，无论I-II期还是III-IV期患者，MDM2和p53高表达均与OSCC患者的OS和DFS不良显著相关。单因素和Cox多因素分析均显示，p53和MDM2可作为OSCC患者预后的独立因素。最后，我们对MDM2的FISH检测结果显示，MDM2高表达与MDM2扩增显著相关（= 0.015）。
结论
本研究表明，MDM2和p53可作为食管鳞状细胞癌患者预后的独立预测指标。
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