Circulating resistin in early-onset breast cancer patients with normal body mass index correlate with disease-free survival and lymph node involvement

Zeidan, Bashar, Manousopoulou, Antigoni, Garay-Baquero, Diana, White, Cory, Larkin, Samantha, Roumeliotis, Theodoros, Papachristou, Evangelia, Copson, Ellen, Cutress, Ramsey, Potter, Kathleen, Beers, Stephen, Eccles, Diana, Townsend, Paul and Garbis, Spiros (2018) Circulating resistin in early-onset breast cancer patients with normal body mass index correlate with disease-free survival and lymph node involvement. European Journal of Surgical Oncology, 44 (6), 905-905. (doi:10.1016/j.ejso.2018.02.184).

Abstract

Introduction: early-onset breast cancer (EOBC) affects about one in 300 women aged 40 years or less and is associated with worse outcomes than later onset breast cancer. This study explored serum protein markers of adverse prognosis in patients with EOBC.

Methods: serum samples from EOBC patients (stages 1-3) were analysed using non-targeted quantitative proteomics. All patients received anthracycline-based chemotherapy. The discovery cohort (n=399) either had more than five-year disease-free survival (DFS) (good outcome group, n=203) or DFS of less than two years (poor outcome group, n=196). Expressed proteins were assessed for differential expression between the two groups. ELISA analysis against an independent sample set from the POSH cohort (n=181) was used to validate target protein expression. Linear and generalized linear modelling was applied to determine the effect of various clinicopathological factors on outcome.

Results: a total of 5,346 unique proteins were analyzed (FDR p ≤ 0.05). 812 proteins were differentially expressed in the good vs. poor outcome group and showed significant enrichment for the insulin signalling and the glycolysis/ gluconeogenesis (p=0.01) pathways. A consistent nodal protein to these metabolic networks was resistin (upregulated in the good outcome group, p=0.009). ELISA validation demonstrated resistin to be upregulated in the good outcome group (p=0.04), irrespective of BMI and ER status. LN involvement was the only covariate with a significant association with resistin measurements (p=0.004). Survival analysis showed that resistin overexpression was associated with improved DFS.

Conclusions: low resistin levels in EOBC may be a surrogate indicator of worse breast cancer specific prognosis.

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Contributors

Author: Diana Garay-Baquero

Author: Stephen Beers

Author: Diana Eccles

Author: Spiros Garbis

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