An Quanming, Miao Lili, Wu Jia, Ma Junwen
Department of Gastrointestinal Surgery, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
Department of Respiratory and Critical Care Medicine,The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
J Cancer. 2025 Jan 1;16(3):860-875. doi: 10.7150/jca.98563. eCollection 2025.
The TP53 mutation is a poor prognostic factor for malignant tumors in a number of organs. The present study primarily aimed to clarify the impact of the mutant pattern of p53 on the prognosis and recurrence of gastric cancer. : For this purpose, 519 patients who underwent radical gastrectomy for cancer were enrolled in the present study. Immunohistochemistry (IHC) was used to examine p53 expression in tissues and a three-stage classification system was used to divide the patient tissues into three groups according to the expression of p53: Heterogeneous (wild-type), absent and overexpression (mutant). After 5 years of follow-up, recurrence and metastasis occurred in 38.7% of patients with stomach cancer, with a p53 mutant pattern in 48.4% of these patients. Patients with a p53 mutant pattern had lower recurrence-free and overall survival rates at 5 years compared with those who were p53 wild-type (P<0.001). It was found that the p53 pattern differed significantly (P<0.001) between the wild-type and mutant patterns, including the pN0 and pN+ gastric cancer subgroups (P<0.001 and P=0.014, respectively). The p53 mutant pattern was also significant in the determination of the recurrence-free survival of patients with progressive stomach cancer (P<0.0001). The 5-year overall survival rates were 71.7 and 36.2%, and the recurrence-free survival rates were 71.2 and 35.2% in the pN0 and pN+ groups, respectively (P<0.001). The mutant pattern of p53 was a significant prognostic factor for both distant metastasis [relative risk (RR)=2.881, P<0.001] and overall survival (RR=2.809, P<0.001) in the univariate Cox regression analysis. In the multivariate analysis, distant metastasis (RR=2.767, P<0.001) remained significant in the mutant pattern of p53 staining. After propensity score matching, 189 patients with a p53 wild-type and 189 patients with a p53 mutant pattern were extracted for analysis. The 5-year overall survival rate in patients with the p53 mutant pattern (n = 189) was worse than that in the patients with p53 wild-type (n = 189) and with significant differences (log-rank P<0.01). The study was statistically significant after Cox univariate and multivariate regression analysis, which revealed that the mutant pattern of p53 is an independent prognostic factor impacting distant metastases following curative gastrectomy for advanced-stage gastric cancer (p = 0.48).
TP53突变是许多器官恶性肿瘤的不良预后因素。本研究主要旨在阐明p53突变模式对胃癌预后和复发的影响。为此，本研究纳入了519例行胃癌根治术的患者。采用免疫组织化学（IHC）检测组织中p53的表达，并根据p53的表达情况，使用一个三阶段分类系统将患者组织分为三组：异质性（野生型）、缺失和过表达（突变型）。经过5年的随访，38.7%的胃癌患者发生了复发和转移，其中48.4%的患者具有p53突变模式。与p53野生型患者相比，具有p53突变模式的患者5年无复发生存率和总生存率较低（P<0.001）。发现野生型和突变型之间的p53模式存在显著差异（P<0.001），包括pN0和pN+胃癌亚组（分别为P<0.001和P=0.014）。p53突变模式在进展期胃癌患者无复发生存的判定中也具有显著性（P<0.0001）。pN0组和pN+组的5年总生存率分别为71.7%和36.2%，无复发生存率分别为71.2%和35.2%（P<0.001）。在单因素Cox回归分析中，p53的突变模式是远处转移[相对风险（RR）=2.881，P<0.001]和总生存（RR=2.809，P<0.001）的显著预后因素。在多因素分析中，p53染色的突变模式下远处转移（RR=2.767，P<0.001）仍然具有显著性。经过倾向评分匹配后，提取189例p53野生型患者和189例p53突变模式患者进行分析。p53突变模式患者（n = 189）的5年总生存率低于p53野生型患者（n = 189），且差异具有显著性（对数秩检验P<0.01）。经过Cox单因素和多因素回归分析，该研究具有统计学意义，结果显示p53突变模式是影响晚期胃癌根治术后远处转移的独立预后因素（p = 0.48）。
