Soluble FAS ligand as a biomarker of disease recurrence in differentiated thyroid cancer

• Type of Material: Article
• Authors: Taofeek K Owonikoko, Emory University; Mohammad S Hossain, Emory University; Chandar Bhimani, Emory University; Zhengjia Chen, Emory University; Sungjin Kim, Emory University; Suresh S Ramalingam, Emory University; Shi-Yong Sun, Emory University; Dong M Shin, Emory University; Edmund K Waller, Emory University; Fadlo Khuri, Emory University
• Language: English
• Date: 2013-04-15
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 American Cancer Society
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/cncr.27937/abstract
• Title of Journal or Parent Work: Cancer
• ISSN: 0008-543X
• Volume: 119
• Issue: 8
• Start Page: 1503
• End Page: 1511
• Grant/Funding Information: This work was supported by National Institutes of Health grants 5P50CA128613 (principal investigator, Dong M. Shin, MD), 1K23CA164015 (principal investigator, Taofeek K. Owonikoko, MD, PhD), and P01 CA116676 (principal investigator, Fadlo Khuri, MD) and by a Georgia Cancer Coalition Distinguished Cancer Scholar Award (principal investigator, Taofeek K. Owonikoko, MD, PhD).
• Keywords: recurrence; FASL; cancer; biomarker; Thyroid
• Research Categories: Health Sciences, Oncology; Biology, Bioinformatics

Abstract

Background Reliable predictive biomarkers are required to address the challenge of disease recurrence following thyroid cancer surgery. We assessed the association of cellular- and serum-based immunologic mediators with thyroid cancer recurrence. Methods Leukocyte subset counts and immune regulatory cytokines were determined in peripheral blood samples using multiparameter flow cytometry and 51-panel multiplex ELISA (Luminex) assays, respectively. Functional activity of circulating B-, T- and NK lymphocytes was assessed ex vivo. Differences in mean biomarker levels between defined subject groups and correlations between biomarkers and cancer recurrence were assessed by t-test or Wilcoxon test and by univariate and multivariate analyses with Cox model. Optimal cut-off values of significantly correlated biomarkers that best predict recurrence post surgery were established by receiver operating characteristics and validated by the optimal cut-point determination algorithm. Results We enrolled 35 patients (median age - 49.4 years; 24 females; 15 patients with disease recurrence) and 21 controls. Patients without recurrence had higher levels of soluble FAS ligand (sFASL), TGF-b, T-regs and PD-1/PD-L1 expressing leukocytes. sFASL (HR:0.60; 95%CI:0.38–0.95; p=0.031) and IFN-α (HR:1.55; 95%CI:1.03–2.34; p=0.038) showed significant association with cancer recurrence. There was a significant difference in PFS between patient groups stratified by sFASL optimal cut-point of 15 pg/ml (Logrank p=0.0009). Conclusions sFASL and IFN-α showed significant correlation with thyroid cancer recurrenceand may be useful for risk-adapted surveillance strategies for thyroid cancer.