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晚期非小细胞肺癌中 TP53 共突变的临床特征及其预后意义。

The clinical features and prognostic implications of the co-mutated TP53 gene in advanced non-small cell lung cancer.

机构信息

Tai'an City Central Hospital (Tai'an Central Hospital Affiliated to Qingdao University, Mount Taishan Medical Center), Tai'an, 271000, Shandong, China.

Department of Respiratory Medicine, The Second Affiliated Hospital of Shandong First Medical University, No. 336 Taishan Street, Taishan District, Tai'an, 271000, Shandong, China.

出版信息

Clin Transl Oncol. 2024 Dec;26(12):3236-3245. doi: 10.1007/s12094-024-03533-1. Epub 2024 Jun 13.

Abstract

BACKGROUND

TP53 is a frequently mutated oncogene within non-small cell lung cancer (NSCLC). However, the clinical and prognostic significance of co-mutations in TP53 in patients with advanced NSCLC has not been fully elucidated.

METHODS

A total of 174 patients with advanced NSCLC were enrolled in this study. All patients were subjected to sequencing analysis of tumor-related genes and information such as PD-L1 expression, TMB, and co-mutation changes were collected. Patients were categorized into TP53 mutant and TP53 wild-type groups according to their TP53 mutation status and then statistically analyzed.

RESULTS

TP53 mutations were the most common among all patients, accounting for 56.32%, followed by epidermal growth factor receptor mutations at 48.27%. The most common mutation sites in the TP53 mutation group were exons 5-8.TP53 mutations were significantly associated with PD-L1 and TMB levels. Univariate Cox analysis showed that gender and EGFR mutation affected the prognosis of TP53-mutated NSCLC patients, and multivariate Cox regression analysis identified EGFR mutation as an independent risk factor. The OS of NSCLC patients in the TP53 mutation group was significantly shorter than that of the TP53wt group. Survival curves in the TP53/EGFR combined mutation group showed that patients with combined EGFR mutation had a lower survival rate.

DISCUSSION

TP53 mutations are associated with different clinical indicators and have important implications in clinical treatment. TP53 is a poor prognostic factor for NSCLC patients, and TP53/EGFR co-mutation will affect the survival time of patients. TP53/EGFR co-mutation may be a new prognostic marker for NSCLC.

摘要

背景

TP53 是非小细胞肺癌(NSCLC)中经常发生突变的癌基因。然而,晚期 NSCLC 患者中 TP53 共突变的临床和预后意义尚未完全阐明。

方法

本研究共纳入 174 例晚期 NSCLC 患者。所有患者均接受肿瘤相关基因测序分析,并收集 PD-L1 表达、TMB 和共突变变化等信息。根据 TP53 突变状态将患者分为 TP53 突变组和 TP53 野生型组,并进行统计学分析。

结果

TP53 突变是所有患者中最常见的突变,占 56.32%,其次是表皮生长因子受体突变,占 48.27%。TP53 突变组中最常见的突变部位是外显子 5-8。TP53 突变与 PD-L1 和 TMB 水平显著相关。单因素 Cox 分析显示,性别和 EGFR 突变影响 TP53 突变型 NSCLC 患者的预后,多因素 Cox 回归分析确定 EGFR 突变为独立危险因素。TP53 突变组 NSCLC 患者的 OS 明显短于 TP53wt 组。TP53/EGFR 联合突变组的生存曲线表明,联合 EGFR 突变的患者生存率较低。

讨论

TP53 突变与不同的临床指标相关,对临床治疗具有重要意义。TP53 是 NSCLC 患者的不良预后因素,TP53/EGFR 共突变会影响患者的生存时间。TP53/EGFR 共突变可能是 NSCLC 的一个新的预后标志物。

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