Related Experiment Video
Updated: Oct 10, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Prognostic phenotypes of early-stage lung adenocarcinoma
Anne-Sophie Lamort1,2,3, Jan Christian Kaiser4,3, Mario A A Pepe1,2
1Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich-German Research Center for Environmental Health (HMGU), Munich, Germany.
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 a median of 2.34 (95% CI 1.71-3.49) years.
Results:
Unsupervised hierarchical clustering revealed two patient subgroups with similar clinicopathological 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 (hazard ratio 2.23, 95% CI 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 The Cancer Genome Atlas and KMplotter data, and showed prognostic power supplementary to International Association for the Study of Lung Cancer tumour-node-metastasis stage and World Health Organization histologic classification.
Conclusions:
Two molecular subtypes of LUAD exist and their identification provides important prognostic information.
