Soluble Interleukin 6 Receptor: A Serum Biomarker Predicting Preoperative Chemoradiotherapy Efficacy for Oesophageal Cancer

ABSTRACT Background Preoperative chemoradiotherapy (PCRT) was one of the standard care for resectable esophageal cancer. Because there is tendency of high morbidity at surgery after PCRT, risk benefit balance for PCRT should be considered.Predictive marker which can select the patients who have more benefit for PCRT is needed. Methods To identify a biomarker to predict efficacy of preoperative PCRT for esophageal cancer, expression profiles of serum proteins were determined. The expression levels of 84 serum proteins in 37 patients (7 responders to PCRT and 30 poor-responders) weremeasured. Responders were defined as the patients whom two third or more cancer was pathologically degenerated at the time of operation. The usefulness of biomarkers was validated with two independent retrospective cohorts (PCRT and preoperative chemotherapy (PCT) by cisplatin and 5-FU) and two phase II clinical cohorts (PCRT and PCT with docetaxel, cisplatin and 5-FU) (n = 187). Results In a discovery cohort, the expression levels of six proteins [macrophage inflammatory protein beta 1 (MIP1B), soluble interleukin 6 receptor (sIL6R), macrophage inflammatory protein alpha1 (MIP1A), insulin, interferon alpha 2 (IFNA2) and matrix metalloproteinase 3 (MMP3)] were significantly different between responders and poor-responders to PCRT. The most predictive factor for survival was soluble interleukin 6 receptor (sIL6R) (p = 0.008, log-rank test); sIL6R in poor-responders was higher than in responders (p = 0.005, Student's t-test). The increases of sIL6R in poor-responder who underwent PCRT were confirmed in a etrospective cohort (n = 38), and a phase II clinical trial (n = 26). However, sIL6R levels of patients who underwent PCT only in a retrospective cohort (cisplatin and 5FU n = 100) and a phase II clinical trial (docetaxel, cisplatin and 5FU, n = 23) were not significantly different. Conclusion Serum sIL6R have a potential to be a predictive biomarker for PCRT in esophageal cancer patients, not for preoperative chemotherapy. Disclosure All authors have declared no conflicts of interest.