SAT-349 Expression of Cyclin B1, Transferrin Receptor and Fibronectin Correlates with the Prognosis of Patients with Adrenal Cortical Carcinoma

Adrenal cortical carcinoma (ACC) is a rare cancer with poor prognosis. The main treatment of ACC is surgery, and the role of systemic chemotherapy is limited. However, up to 74% of patients are known to experience recurrence after surgery, even following complete resection (1). Therefore, it is important to know the biomarkers which can predict the prognosis beyond clinical stages. Previous studies have reported several prognostic factors of ACC including Ki67 and markers revealed by multi-omics approaches (2-4). However, the proteomic approach for predicting prognosis has not been investigated. Therefore, we aimed to investigate the prognostic biomarkers for ACCs using proteomic approach. We used the reverse phase protein array data from The Cancer Proteome Atlas. Differentially expressed proteins in metastatic and non-metastatic ACCs were identified using Benjamini-Hochberg method. We validated the identified proteins using the multivariate Cox’s proportional hazard regression analysis for metastasis including age and clinical staging. Additive prognostic values were analyzed using C-index and category free Net reclassification index (cfNRI). Among 46 ACC patients, cyclin B1, transferrin receptor (TFRC) and fibronectin were significantly overexpressed in patients with distant metastasis. In the Cox regression model, during median follow-up of 3.1 years, high expression status of cyclin B1 and TFRC were significantly associated with high mortality (hazard ratios [HR] (95% confidence interval [CI]), 6.13 (1.02-36.7), and 6.59 (1.14-38.2), respectively). However, high expression status of fibronectin was not associated with mortality (HR [95% CI], 3.92 [0.75-20.4]). When we combined protein expression signatures, high cyclin B1/high TFRC, high cyclin B1/high fibronectin and high TFRC/high fibronectin were highly associated with mortality: HR (95% CI) 13.72 (1.89-99.66), HR 9.22 (1.34-63.55) and HR 18.59 (2.54-135.88), respectively. Compared to age and staging model, addition of cyclin B1, TFRC, fibronectin, or combination of these proteins models all improved the risk prediction by C-index (0.780 to 0.818~0.864) and cfNRI (0.741~1.027, all P<0.05). Among ACC patients, overexpression of various combinations of cyclin B1, TFRC and fibronectin proteins were associated with poor prognosis. Also, these combinatory biomarkers showed additive prognostic values beyond age and clinical staging, and combination of cyclin B1 and TFRC showed poorest prognosis and highest predictive value among them. Thus, the combination of these three proteins can be useful prognostic markers for ACC. Reference: (1) Freire DS et al., Clin Endocrinol (Oxf). 2013 Oct;79(4):468-75. (2) Beuschlein F et al., J Clin Endocrinol Metab. 2015 Mar;100(3):841-9. (3) Assié G et al., Nat Genet. 2014 Jun;46(6):607-12. (4) Zheng S et al., Cancer Med. 2016 Aug;5(8):2117-25.