Objective: To construct a diagnostic signature to distinguish lung adenocarcinoma from lung squamous cell carcinoma and a prognostic signature to predict the risk of death for patients with nonsmall-cell lung cancer, with satisfactory predictive performances, good stabilities, small sizes and meaningful biological implications.
Methods: Pathway-based feature selection methods utilize pathway information as a priori to provide insightful clues on potential biomarkers from the biological perspective, and such incorporation may be realized by adding weights to test statistics or gene expression values. In this study, weighted gene expression profiles were generated using the GeneRank method and then the LASSO method was used to identify discriminative and prognostic genes.
Results: The five-gene diagnostic signature including keratin 5 (KRT5), mucin 1 (MUC1), triggering receptor expressed on myeloid cells 1 (TREM1), complement C3 (C3) and transmembrane serine protease 2 (TMPRSS2) achieved a predictive error of 12.8% and a Generalized Brier Score of 0.108, while the five-gene prognostic signature including alcohol dehydrogenase 1C (class I), gamma polypeptide (ADH1C), alpha-2-glycoprotein 1, zinc-binding (AZGP1), clusterin (CLU), cyclin dependent kinase 1 (CDK1) and paternally expressed 10 (PEG10) obtained a log-rank P-value of 0.03 and a C-index of 0.622 on the test set.
Conclusions: Besides good predictive capacity, model parsimony and stability, the identified diagnostic and prognostic genes were highly relevant to lung cancer. A large-sized prospective study to explore the utilization of these genes in a clinical setting is warranted.
Keywords: GeneRank; Lung adenocarcinoma; classification; pathway information; prognosis; squamous cell carcinoma.