Cold-inducible RNA-binding protein is associated with subtype-specific breast cancer patient outcomes.

Abstract

Background: Cold-inducible RNA-binding protein (CIRBP) is a stress-induced mRNA-binding protein associated with clinical outcomes in a variety of human disease states. The role of CIRBP as a role as a prognostic biomarker in breast cancer (BC) has yet to be established.

Findings: We describe a clinically annotated tissue micro-array cohort of 1406 hormone receptor positive (HR +) and 281 triple negative primary breast cancers (TNBC) stained by immunohistochemistry (IHC) for CIRBP. Statistical analyses were performed with the Kaplan-Meier estimator, as well as univariate and multivariate Cox proportional-hazards models. Multivariate models incorporated tumor size, lymph node status, grade and CIRBP expression levels. Co-primary endpoints were overall survival (OS) and progression-free survival (PFS). In N = 281 primary TNBCs, high levels of CIRBP expression by IHC was associated with poor prognosis in multivariate analysis (OS: adjusted hazard ratio (aHR) 2.05, 95% confidence interval (CI) 1.24-3.41, P = 0.005. PFS: aHR 2.46, 95% CI 1.33-4.57, P = 0.004). However, in N = 1406 HR + primary BC, CIRBP expression was correlated with favorable prognosis (OS: aHR 0.927, 95% CI 0.88-0.98, P = 0.005. PFS: aHR 0.904, 95% CI 0.85-0.96, P = 0.002).

Conclusions: CIRBP expression is associated with poor prognosis in TNBC but not HR + BC patients. This finding highlights the prognostic significance of CIRBP in TNBC and suggests differential underlying mRNA targets bound and modulated by CIRBP in TNBC and HR + BC, respectively.