Δ133p53/FLp53 Predicts Poor Clinical Outcome in Esophageal Squamous Cell Carcinoma

Abstract

Qimin Tu,1,2,* Hongjian Gong,3,4,* Chunhui Yuan,3 Gao Liu,5 Jinqi Huang,1 Zhichao Li,4 Jianfei Luo2 1Department of Cardio-Thoracic Surgery, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, People’s Republic of China; 2Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Clinical Research Center, Wuhan Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 4Department of Rheumatism Immunology, Wuhan Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5Department of Gastrointestinal Surgery, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhichao LiDepartment of Rheumatism Immunology, Wuhan Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaTel [phone]Email [email protected] LuoDepartment of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of ChinaTel [phone]Email [email protected]: p53 isoform Δ 133p53 is directly transactivated by p53 and antagonizes p53 activities in cancer progression. However, its correlation with prognosis and cancer recurrence in esophageal squamous cell carcinoma (ESCC) is still unclear.Patients and Methods: Expression of Δ 133p53 and Δ 133p53/full-length p53 (FLp53) in tissues and serums of 180 ESCC patients was evaluated using qRT-PCR. Patients were divided into high- and low-expression groups according to the cutoff value determined by X-tile 3.6.1 software. Survival analysis was performed by the Kaplan–Meier method. Univariate and multivariate Cox survival analyses were applied to assess the hazard ratios (HRs).Results: Tissue Δ 133p53 expression and Δ 133p53/FLp53 ratio were significantly increased in ESCC tissue compared with adjacent normal tissue. Pre-operative Δ 133p53 expression and Δ 133p53/FLp53 ratio in tissue or serum samples were positively associated with TNM stage and post-operative recurrence. Kaplan–Meier curve and multivariate cox regression analyses revealed that the tissue and serum Δ 133p53/FLp53 ratios (cutoff value: 2.9160) were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) in ESCC patients and showed no statistical difference in receiver-operating characteristic curve (ROC) analysis, while serum Δ 133p53 showed no significant prognostic value. More importantly, the serum Δ 133p53/FLp53 ratio in ESCC patients was significantly decreased within 72 h post tumor resection and patients with a consistently high serum Δ 133p53/FLp53 ratio (≥ 2.9160) had higher recurrence rates than those with consistently low ratio values. In addition, dynamic detection in each follow-up timepoint showed that serum Δ 133p53/FLp53 ratios were higher than 2.9160 upon recurrence, and they even increased prior to radiologic progression.Conclusion: The serum Δ 133p53/FLp53 ratio can be a novel predictor for survival outcome and may serve as a real-time parameter for monitoring recurrence in ESCC patients after surgery.Keywords: esophageal squamous cell carcinoma, p53, Δ 133p53, prognosis, recurrence

Keywords

• esophageal squamous cell carcinoma
• p53
• δ133p53
• prognosis
• recurrence