The High Expression of p53 Is Predictive of Poor Survival Rather TP53 Mutation in Esophageal Squamous Cell Carcinoma

Author:

Jin Yan12,Zhao Xueke1,Song Xin1,Wang Ran1,Fan Zongmin1,Wang Panpan1,Yang Miaomiao1,Zhou Fuyou3,Bao Qide4,Wang Lidong1ORCID

Affiliation:

1. State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China

2. Department of Human Anatomy & Histoembryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China

3. Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang, China

4. Department of Oncology, Anyang District Hospital of Puyang City, Anyang, China

Abstract

TP53 is a well-known tumor suppressor gene and one of the most common genetic alterations in human cancers. However, the role of p53 as a prognostic marker of esophageal squamous cell carcinoma (ESCC) is controversial in the association between TP53 alterations and clinical outcomes. To address this issue, we evaluated TP53 mutations, p53 protein expression, clinicopathological parameters, and survivals rates in a large scale of patients with ESCC. Two cohorts were included in this study: TP53 mutations were detected by next-generation sequencing in 316 ESCC patients, and p53 protein expression was tested by immunohistochemistry in 6,028 ESCC patients. Survival analysis was performed using the Kaplan–Meier curve and the Cox proportional hazards model. TP53 mutations were found in ESCC patients from 241 of 316 (76.3%), and the rate of positive expression of p53 protein was 59.1% in 6,028 ESCC patients (including 1819 with high expression of p53 protein), respectively. Most mutations were missense, which has a high expression of p53 protein. Compared with wild-typeTP53, TP53 gene mutations were not significantly associated with survival time ( p = 0.083 ). In multivariate analysis, the p53 protein expression was an independent prognostic factor for ESCC. The high-expression group of p53 protein has poor survival ( p < 0.001 ) compared to low-expression group in patients with ESCC. The high expression of the p53 protein, not the TP53 mutation, is predictive of poor survival in patients with ESCC, and p53 protein expression might have the potential to be a prognosis biomarker and therapy target in ESCC.

Funder

National Basic Research Program of China

Publisher

Hindawi Limited

Subject

Oncology

Reference49 articles.

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