Translating Gene Signatures Into a Pathologic Feature: Tumor Necrosis Predicts Disease Relapse in Operable and Stage I Lung Adenocarcinoma

Summary

This multi-cohort analysis demonstrates that three molecular gene signatures (cell cycle, hypoxia, and mTOR pathway activity) are mutually interdependent in lung adenocarcinoma and correlate with the pathologic feature of tumour necrosis, which independently predicts shorter overall and relapse-free survival in patients with operable stage I disease. The findings suggest that translating gene signatures into measurable pathologic features offers improved risk stratification beyond conventional staging parameters in early-stage lung adenocarcinoma. The work integrates genomic and proteomic data to validate that signature scores reflect genuine pathway activity differences between necrotic and non-necrotic tumours.

UK applicability

The prognostic markers identified could potentially inform clinical practice in UK lung cancer services to better stratify stage I adenocarcinoma patients for adjuvant therapy consideration and surveillance intensity. However, implementation would require validation in UK-based cohorts and integration with existing National Health Service pathology and genomic infrastructure.

Key measures

Gene signature activity scores; tumour necrosis status (presence/absence); overall survival; relapse-free survival; protein expression levels from The Cancer Protein Atlas; mutual interdependence of signatures

Outcomes reported

The study examined whether three gene signatures (cell cycle, hypoxia, and mTOR) translate into a pathologic feature—tumour necrosis—that predicts disease relapse and survival outcomes in patients with operable and stage I lung adenocarcinoma. The analysis assessed risk stratification power across nine lung adenocarcinoma cohorts and five squamous cell carcinoma cohorts, with validation in The Cancer Genome Atlas.

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