PURPL is associated with adverse clinical outcome in Luminal A breast cancer

Abstract

IntroductionLuminal A is the most common breast cancer molecular subtype and is generally associated with a favorable five-year prognosis. However, a substantial subset of patients experience relapse, suggesting that biologically distinct high-risk tumors exist within this subtype. MethodsWe applied Topological Analysis of Array Comparative Genomic Hybridization (TAaCGH) to identify recurrent copy number alterations associated with Luminal A breast cancer. We subsequently evaluated the long non-coding RNA PURPL using copy number, gene expression, and survival data in the independent TCGA, METABRIC, and SCAN-B cohorts. Associations with clinical outcome were examined using multivariable Cox regression and TP53-stratified analyses. ResultsPURPL copy number gain was associated with significantly worse survival in TCGA and METABRIC, while elevated PURPL expression was associated with significantly worse survival in TCGA and SCAN-B. Elevated PURPL expression remained associated with survival after adjustment for clinical covariates. In analyses stratified by TP53 mutation status, high PURPL expression remained associated with worse survival in TP53 wild-type tumors. Although PURPL has previously been implicated in cancer-related mechanisms, its copy number alteration, expression, and association with clinical outcome have not been systematically evaluated in Luminal A breast cancer. ConclusionThese findings identify PURPL as a candidate lncRNA within a recurrent copy number alteration associated with adverse clinical outcome in Luminal A breast cancer and support further mechanistic investigation of its role in this subtype.