A cyclooxygenase-2 associated pro-tumorigenic inflammatory signature predicts outcome after surgery in lung cancer
Fife, V.; Bromley, C. P.; Roberts, M.; Lee, I. C. H.; Grainger, D.; Chaturvedi, A.; Zhou, C.; Fife, C. M.; Morris, K.; Fuertes Gassio, A.; Atkinson, S.; Sivagnanam, S.; Betre, K.; Cheeseman, A. J.; Crowther, M.; Wan, J. C. M.; Karasaki, T.; Millrine, D.; Kilgour, E.; McGranahan, N.; Jamal-Hanjani, M.; Swanton, C.; TRACERx consortium, ; Coussens, L. M.; Crosbie, P. A. J.; Dive, C.; Zelenay, S.
Show abstract
With increased lung cancer screening, early-stage diagnoses and recurrences are expected to rise. Identifying the ~20% of patients with early-stage non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), who relapse after curative-intent surgery remains a major clinical challenge. Here, we identify a COX-2-associated pro-tumorigenic inflammatory signature (PTI) in resected tumors as an independent predictor of disease relapse in both LUAD and LUSC, with particular utility within one year after surgery in stage I NSCLC. We developed a clinically compatible workflow for PTI scoring in tumor resections and validated its predictive performance in real-world samples from routine care and screening programs. Spatial immune profiling revealed that PTIhigh tumors, which swiftly recur, exhibit markedly reduced tumor cell content alongside expanded neutrophil-rich immune-stromal compartments. These findings link COX-2-driven inflammation to early post-surgical recurrence in NSCLC and indicate that PTI may serve as a biomarker for risk stratification to guide imaging surveillance and adjuvant therapy decisions.
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