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Concurrent mutations in multiple tumor suppressor genes correlate with adverse prognosis in stage I lung adenocarcinoma patients

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资源类型：
Pubmed体系：
作者：
Wang Yuan[1,2] * ; Xu Renjie[2,3] ; Ren Jing[2,4] ; Li Yuanjie[2] ; Chen Yaoxi[2] ; Zhang Li[1,2,3] ; Qiu Zhixin[2,3,*1] ;
机构： [1]Department of Pulmonary and Critical Care Medicine/Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. [2]Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital of Sichuan University, Chengdu, China. [3]Department of Pulmonary and Critical Care Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China. [4]The Integrated Care Management Center, West China Hospital of Sichuan University, Chengdu, China.
出处：
DOI： 10.21037/jtd-2025-29
ISSN：

关键词： Lung adenocarcinoma (LUAD) TP53 tumor suppressor gene (TSG) prognostic factors recurrencefree survival (RFS)

摘要：
Early-stage lung adenocarcinoma exhibits high postoperative recurrence rates, yet the role of TP53 co-mutations with other tumor suppressor genes (TSGs) in driving this risk remains elusive. We aim to elucidate the relationship between different TP53/TSG statuses and recurrence-free survival (RFS) and optimize treatment and follow-up strategies of early-stage patients.Patients with stage I lung adenocarcinoma who underwent resection at West China Hospital of Sichuan University were categorized into three groups: TP53+/TSG+ (co-mutations), TP53+/TSG- (only TP53 mutation), and TP53-. Kaplan-Meier and Cox regression models assessed the association between TP53/TSG status and RFS, with validation from Memorial Sloan Kettering (MSK) cohort. Hazard function estimation described changes in recurrence risk over time.Among 618 patients, 130 had TP53 mutations (TSG+: 21 vs. TSG-: 109). TP53+ patients were more inclined to be smokers and male compared to TP53- patients (all P<0.001). In MSK dataset, TP53+/TSG+ group had the highest smoking rate (all P<0.05). TP53+ tumors showed higher rates of spiculation, pleural indentation, and visceral pleural invasion (all P<0.05). Recurrence occurred in 45 patients (7.3%). TP53+/TSG+ patients exhibited shorter RFS than both TP53+/TSG- and TP533- groups (our cohort: 14.7 vs. 25.6 vs. 30.5 months, P<0.001; MSK cohort: 11.2 vs. 19.9 vs. 14.9 months, P=0.005). Multivariate Cox analysis confirmed TP53+/TSG+ as an independent risk factor for relapse [TP53+/TSG+ vs. TP53+/TSG-, hazard ratio (HR) = 3.0, 95% confidence interval (CI): 1.2-7.6, P=0.02; TP53+/TSG+ vs. TP53-, HR =3.0, 95% CI: 1.2-7.2, P=0.01]. Tumor mutation burden elevated in TP53+/TSG+ patients (all P<0.05), with a spike in recurrence risk at 3-4 years.TP53+/TSG+ patients exhibit higher recurrence risk, highlighting the need for close surveillance and further research into the potential role of neoadjuvant strategies.Copyright © 2025 AME Publishing Company. All rights reserved.

基金：
This study was supported by National Natural Science Foundation of China (CN) (No. 82370100), and National Science and Technology Innovation 2030 Major Project for Prevention and Treatment of Cancer, Cardiovascular, Respiratory and Metabolic Diseases (Nos. 2023ZD0506100, and 2023ZD0506106)
语种：
外文
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出版当年[2025]版：
大类 | 4 区 医学
小类 | 4 区 呼吸系统
最新[2025]版：
大类 | 4 区 医学
小类 | 4 区 呼吸系统
第一作者：
第一作者机构： [1]Department of Pulmonary and Critical Care Medicine/Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital of Sichuan University, Chengdu, China. [2]Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital of Sichuan University, Chengdu, China.
通讯作者：
通讯机构： [2]Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital of Sichuan University, Chengdu, China. [3]Department of Pulmonary and Critical Care Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China. [*1]Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital of Sichuan University, Chengdu, China ,Department of Pulmonary and Critical Care Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu 610041, China
推荐引用方式(GB/T 7714)：
Wang Yuan,Xu Renjie,Ren Jing,et al.Concurrent mutations in multiple tumor suppressor genes correlate with adverse prognosis in stage I lung adenocarcinoma patients[J].Journal Of Thoracic Disease.2025,17(9):6873-6883.doi:10.21037/jtd-2025-29.
APA：
Wang Yuan,Xu Renjie,Ren Jing,Li Yuanjie,Chen Yaoxi...&Qiu Zhixin.(2025).Concurrent mutations in multiple tumor suppressor genes correlate with adverse prognosis in stage I lung adenocarcinoma patients.Journal Of Thoracic Disease,17,(9)
MLA：
Wang Yuan,et al."Concurrent mutations in multiple tumor suppressor genes correlate with adverse prognosis in stage I lung adenocarcinoma patients".Journal Of Thoracic Disease 17..9(2025):6873-6883

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