title: Critical limitations of prognostic signatures based on risk scores summarized from gene expression levels: a case study for resected stage I non-small-cell lung cancer.
abstract: Most of current gene expression signatures for cancer prognosis are based on risk scores, usually calculated as some summaries of expression levels of the signature genes, whose applications require presetting risk score thresholds and data normalization. In this study, we demonstrate the critical limitations of such type of signatures that the risk scores of samples will change greatly when they are normalized together with different samples, which would induce spurious risk classification and difficulty in clinical settings, and the risk scores of independent samples are incomparable if data normalization is not adopted. To overcome these limitations, we propose a rank-based method to extract a prognostic gene pair signature for overall survival of stage I non-small-cell lung cancer. The prognostic gene pair signature is verified in three integrated data sets detected by different laboratories with different microarray platforms. We conclude that, different from the type of signatures based on risk scores summarized from gene expression levels, the rank-based signatures could be robustly applied at the individualized level to independent clinical samples assessed in different laboratories.
authors.forename: Lishuang
authors.initials: L
authors.lastname: Qi
authors.forename: Libin
authors.initials: L
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qin
authors.forename: Rufei
authors.initials: R
authors.lastname: Pan
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Zhao
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Gu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.forename: Ruiping
authors.initials: R
authors.lastname: Wang
authors.forename: Xiangqi
authors.initials: X
authors.lastname: Chen
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality* / Q000601:surgery*; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery*; D009367:Neoplasm Staging; D015995:Prevalence; D011379:Prognosis; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: gene pair; limitation of the gene expression signatures; non-small-cell lung cancer; prognosis; relative rank of gene expressions