A Novel Strategy to Identify Prognosis-Relevant Gene Sets in Cancers

Molecular prognosis markers hold promise for improved prediction of patient survival, and a pathway or gene set may add mechanistic interpretation to their prognostic prediction power. In this study, we demonstrated a novel strategy to identify prognosis-relevant gene sets in cancers. Our study consists of a first round of gene-level analyses and a second round of gene-set-level analyses, in which the Composite Gene Expression Score critically summarizes a surrogate expression value at gene set level and a permutation procedure is exerted to assess prognostic significance of gene sets. An optional differential coexpression module is appended to the two phases of survival analyses to corroborate and refine prognostic gene sets. Our strategy was demonstrated in 33 cancer types across 32,234 gene sets. We found oncogenic gene sets accounted for an increased proportion among the final gene sets, and genes involved in DNA replication and DNA repair have ubiquitous prognositic value for multiple cancer types. In summary, we carried out the largest gene set based prognosis study to date. Compared to previous similar studies, our approach offered multiple improvements in design and methodology implementation. Functionally relevant gene sets of ubiquitous prognostic significance in multiple cancer types were identified.