Interleukin-4 Levels Predict Survival Independent of Pathologic Stage in a Mixed Esophageal Cancer Cohort

Abstract

INTRODUCTION: Esophageal cancer (EC) is known to originate in the setting of chronic inflammation. While previous studies have sought to understand the role of inflammatory signaling in EC, little is known regarding the effect of these immunologic changes on patient outcomes. Several studies have linked serum cytokine levels with prognostic measures; however, these studies consist primarily of patients with esophageal squamous cell carcinoma (ESCC) with few esophageal adenocarcinoma (EAC) cases. The objective was to evaluate the relationship between serum cytokine levels and survival in patients with EC and to validate these findings at the RNA level. METHODS: 37 serum cytokines were profiled at time of resection using multiplex ELISA in 47 patients (42 EAC, 5 ESCC). Cytokine levels were binarized in relation to the median and assessed using Log-rank tests and Cox Regression models. Findings were validated at the RNA-level using TCGA Esophageal Carcinoma cohort (77 EAC, 81 ESCC). RESULTS: Univariate analysis revealed serum Interleukin-4 (IL-4) was associated with survival (p = 0.042) (Figure). Multivariable analysis showed that high serum IL-4, pathologic stage, and body mass index were strong and independent predictors of survival (p < 0.001, p < 0.001 and p = 0.039). Univariate analysis of IL4 RNA levels revealed that IL4 was associated with survival (p = 0.012). Multivariable analysis showed that high IL4 expression, and post-surgical stage were strong and independent predictors of patient survival (p = 0.01, p < 0.001 respectively).FigureCONCLUSION: These results show that IL4 levels associate with survival in EC. Notably, this relationship is independent of clinical/pathologic staging, indicating its potential as a novel prognostic biomarker in EC.