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Prognostic phenotypes of early-stage lung adenocarcinoma.
Eur. Respir. J. 60:2101674 (2021)
BACKGROUND: Survival after curative resection of early-stage lung adenocarcinoma (LUAD) varies and prognostic biomarkers are urgently needed. METHODS: Large-format tissue samples from a prospective cohort of 200 patients with resected LUAD were immunophenotyped for cancer hallmarks TP53, NF1, CD45, PD-1, PCNA, TUNEL, and FVIII, and were followed for median (95%CI)=2.34 (1.71-3.49) years. RESULTS: Unsupervised hierarchical clustering revealed two patient subgroups with similar clinicopathologic features and genotype, but with markedly different survival: "proliferative" patients (60%) with elevated TP53, NF1, CD45, and PCNA expression had 50% 5-year overall survival while "apoptotic" patients (40%) with high TUNEL had 70% 5-year survival [HR95%CI=2.23 (1.33-3.80); p=0.0069]. Cox regression and machine learning algorithms including random forests built clinically useful models: a score to predict overall survival and a formula and nomogram to predict tumour phenotype. The distinct LUAD phenotypes were validated in TCGA and KMplotter data and showed prognostic power supplementary to IASLC TNM stage and WHO histologic classification. CONCLUSIONS: Two molecular subtypes of LUAD exist and their identification provides important prognostic information.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0903-1936
e-ISSN
1399-3003
Journal
European Respiratory Journal
Quellenangaben
Volume: 60,
Issue: 1,
Article Number: 2101674
Publisher
European Respiratory Society
Publishing Place
Sheffield
Non-patent literature
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Reviewing status
Peer reviewed