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Updated: Jan 13, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Concurrent mutations in multiple tumor suppressor genes correlate with adverse prognosis in stage I lung
Yuan Wang1,2, Renjie Xu2,3, Jing Ren2,4
1Department 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.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
TP53+/TSG+ patients exhibit higher recurrence risk, highlighting the need for close surveillance and further research into the potential role of neoadjuvant strategies.
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