1178P - Senescence signature affects overall survival in non-small cell lung cancer

Background

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, with adenocarcinoma as the most common histological type. Cellular senescence (CS) is a durable and generally irreversible cell cycle arrest with secretory features, macromolecular damage and altered metabolism elicited in response to different stresses (e.g., DNA damage), and it is generally considered as an endogenous tumor suppressor mechanism. However, senescent cancer cells stay metabolically active and can secrete a plethora of cytokines, growth factors and proteases that can affect the surrounding tumor microenvironment, ultimately leading to cancer relapse and metastasis. As such, the role of CS in cancer is ambiguous.

Methods

In 65 NSCLC patients with adenocarcinoma TNM stage I-III (8^th edition) treated with surgery (n = 65, 100.0%) and stage-dependent adjuvant chemotherapy (n = 24, 36.9%), excluding neoadjuvant chemotherapy, CS was assessed by a combination of four immunohistochemical senescence markers, i.e., lipofuscin, p16^INK4A, p21^WAF1/Cip1 and Ki67, according to the International Cell Senescence Association recommendations. A senescence signature (SS) was defined by the presence of high-level lipofuscin and p16^INK4A or p21^WAF1/Cip1 (≥ 30% NSCLC cells positive) in combination with low-level Ki67 (< 30% NSCLC cells positive) and correlated to clinicopathological parameters and outcomes, including overall (OS) and disease-free survival (DFS).

Results

For TNM stages I-III, the median OS and DFS for patients with a SS (n = 19, 29.2%) compared to patients without a SS (n = 46, 70.8%) was respectively 54.4 versus 88.5 months (p = 0.019) and 33.2 versus 45.7 months (p = 0.144). For TNM stage I and TNM stage II-III, the median OS for patients with a SS compared to patients without a SS was respectively 54.4 versus 88.5 months (p = 0.095) and 41.7 versus 62.1 months (p = 0.161). Cox PH regression showed that a SS is negatively associated with OS (HR = 1.85 (CI 0.99 – 3.48), p = 0.054) after correction for age, TNM stage and adjuvant chemotherapy.

Conclusions

A SS is negatively associated with OS in NSCLC after correction for age, TNM stage and adjuvant chemotherapy. Our database will be expanded to confirm these preliminary results in a larger population.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

University Research Fund (BOF) of the University of Antwerp (FFB180188).

Disclosure

All authors have declared no conflicts of interest.