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Updated: Jun 8, 2026
Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
The Prognostic Impact of Common Molecular Alterations in Resected Lung Adenocarcinoma and Implications for the Tenth
Huatao Tang1, Chaoqiang Deng1, Hang Cao1
1Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Institute of Thoracic Oncology, Fudan University, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Introduction:
Whether gene mutations can be integrated into the forthcoming tenth edition TNM staging system is of great interest. We aimed to validate the prognostic impact of major driver genes and to investigate their potential for refining the TNM framework.
Methods:
Eligible patients were diagnosed between 2008 and 2021. The analysis was restricted to the following four genes: TP53 mutations ("oncogenic/likely oncogenic" annotated by the OncoKB database), EGFR mutations (L858R, exon 19 deletion), KRAS mutations (codons 12, 13, or 61), and ALK fusions. The stage-specific prognostic value of these mutations was determined using the Kaplan-Meier method. The independent prognostic value of these alterations across TNM stages was assessed using Cox proportional hazards regression models.
Results:
A total of 5839 patients were included (ALK, n = 5303; KRAS, n = 4225; EGFR, n = 4212; TP53, n = 2312). EGFR mutations were found in 2304 (54.7%), TP53 mutations in 692 (29.9%), KRAS mutations in 287 (6.8%), and ALK fusions in 243 (4.6%). Overall survival (OS) was significantly better among patients with stage I EGFR-mutated tumors and stages III to IV ALK fusion-positive tumors, whereas patients with stage I TP53-mutated and KRAS-mutated tumors had significantly worse OS. Multivariable analyses confirmed the OS associations with TP53-mutated tumors (stage I hazard ratio [HR] = 2.49), KRAS-mutated tumors (stage I HR = 1.57), and EGFR-mutated tumors (stage I HR = 0.59). In the "upstaging/downstaging" analysis, patients with TP53- or KRAS-mutated stage IA disease exhibited OS comparable to stage IB, supporting an "upstaging" potential. Conversely, patients with stage III to IV ALK fusions had OS comparable to that of stage II, supporting a "downstaging" potential.
Conclusions:
This study suggests that common molecular alterations in lung cancer exhibit prognostic value within specific stages, and, notably, TP53, KRAS, and ALK alterations hold the potential to modify the current staging system. These findings provide a valuable reference for the forthcoming tenth edition TNM staging system.
