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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Clinical impact of STK11 mutation in advanced-stage non-small cell lung cancer
Pietro Rosellini1, Samuel Amintas2, Charline Caumont1
1CHU de Bordeaux, CIC1401, Service de Pharmacologie Médicale, Service de Biologie des tumeurs, Service des Maladies Respiratoires, F-33000 Pessac, France.
Background:
Mutations in STK11/LKB1 gene present a negative impact on tumour immune microenvironment, especially with concomitant activating KRAS mutation. These recent data may explain a decreased response to immunotherapy treatment in STK11 mutant non-small cell lung cancer (NSCLC).
Objective:
The primary objective is to evaluate, in a real-life setting, overall survival (OS) in patients with NSCLC according to the presence of STK11 mutation. The secondary objective is to assess time to treatment failure (TTF) for the first-line chemotherapy or immunotherapy.
Methods:
This observational multicentric study was conducted in Nouvelle-Aquitaine (France), for 24 months. Clinical, histopathological and imagery data were collected in each centre while the next-generation sequencing analysis was performed in Bordeaux Hospital University. Patient's data were longitudinally followed from NSCLC diagnosis date to the occurrence of censoring events (therapeutic failure or death, as applicable) or until the study end date.
Results:
median OS from the first drug administration was significantly longer for STK11wt patients than STK11mut patients (16.2 months [11 - nr] versus 4.7 months [2.5-9.4]; Log-rank test P < 0.001). The Presence of STK11 mutation was significantly associated with shortened OS (RR = 2.26 [1.35-3.79], P = 0.002). First-line TTF was significantly shorter in STK11mut population and the presence of the mutation was significantly associated with an increase in treatment failures (RR = 1.87 [1.21-2.89], P = 0.005). The type of treatment (chemotherapy, immunotherapy) does not influence the amplitude of reduced TTF in patients with STK11mut.
Conclusion:
The presence of STK11 mutation is associated with poor prognosis in NSCLC.
Insights
STK11 mutations in non-small cell lung cancer (NSCLC) are linked to a worse prognosis and shorter survival. This finding impacts treatment strategies for STK11 mutant NSCLC patients.
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- STK11/LKB1 gene mutations negatively affect the tumor immune microenvironment in non-small cell lung cancer (NSCLC).
- Concomitant KRAS mutations exacerbate this effect, potentially explaining reduced immunotherapy response in STK11 mutant NSCLC.
Purpose of the Study:
- To evaluate overall survival (OS) in NSCLC patients based on STK11 mutation status in a real-world setting.
- To assess time to treatment failure (TTF) for first-line chemotherapy or immunotherapy in NSCLC patients with STK11 mutations.
Main Methods:
- An observational, multicentric study conducted over 24 months in Nouvelle-Aquitaine, France.
- Collected clinical, histopathological, and imagery data, with next-generation sequencing for STK11 mutation analysis.
- Longitudinal patient data followed from diagnosis to censoring events (treatment failure or death).
Main Results:
- Median OS was significantly longer for STK11 wild-type (wt) patients (16.2 months) compared to STK11 mutant (mut) patients (4.7 months).
- STK11 mutation presence significantly shortened OS (Hazard Ratio [HR] = 2.26) and TTF (HR = 1.87).
- Treatment type (chemotherapy or immunotherapy) did not alter the reduced TTF in STK11 mutant NSCLC patients.
Conclusions:
- STK11 mutation is a significant indicator of poor prognosis in non-small cell lung cancer.
- The findings highlight the clinical impact of STK11 mutations on NSCLC patient outcomes and treatment response.
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