Circulating Interleukin-6 is Associated with Prognosis and Genetic Polymorphisms of MIR608 in Patients with Esophageal Squamous Cell Carcinoma
Journal
Annals of Surgical Oncology
Journal Volume
25
Journal Issue
8
Pages
2449-2456
Date Issued
2018
Author(s)
Abstract
Background: No effective targeted therapy exists for esophageal squamous cell carcinoma (ESCC), the major cell type of esophageal cancer. The pleiotropic cytokine interleukin (IL)-6 is associated with adverse prognosis of some cancers, and the open reading frame of IL-6 contains an miR-608 microRNA-targeted site. We investigated the correlation of circulating IL-6 levels with prognosis and with the mir608:rs4919510 genetic polymorphism in ESCC. Methods: A total of 213 patients with primary ESCC were enrolled. Plasma IL-6 levels of ESCC patients were analyzed by enzyme-linked immunosorbent assay (ELISA). The patients’ genotypes of mir608:rs4919510 were analyzed using the MassARRAY system, and functional assays were performed by transient overexpression in cells. The cytotoxicity of IL-6 signaling blockers in ESCC cells was analyzed by MTT assay. Results: We found that plasma IL-6 levels significantly correlated with overall survival (p = 0.019), disease recurrence (p = 0.003), and postoperative complications (p =0.002). Patients with the GG genotype of mir608:rs4919510 had a 4.56-fold increased risk of high expression of IL-6 compared with patients with the CC genotype (odds ratio 4.56, 95% confidence interval 1.87–11.09; p =0.001). Transient overexpression of the miR-608?C (miR-608_C) and G variants (miR-608_G) in cancer cells revealed that the miR-608_G variant was less efficient in regulating the expression of IL-6 compared with miR-608_C. Finally, the IL-6 signaling blocker ruxolitinib exhibited effective cytotoxicity in ESCC cells. Conclusions: The results of this study provide a novel direction for a biomarker-based targeted therapy for ESCC. ? 2018, Society of Surgical Oncology.
SDGs
Other Subjects
interleukin 6; microRNA; microRNA 608; ruxolitinib; tofacitinib; unclassified drug; IL6 protein, human; interleukin 6; microRNA; MIRN608 microRNA, human; tumor marker; adult; aged; Article; cancer prognosis; cancer risk; clinical outcome; cytotoxicity; enzyme linked immunosorbent assay; esophageal squamous cell carcinoma; esophageal squamous cell carcinoma cell line; female; genetic polymorphism; genotype; human; human cell; major clinical study; male; MTT assay; overall survival; postoperative complication; recurrent disease; blood; esophagus resection; esophagus tumor; follow up; gene expression regulation; genetics; middle aged; pathology; prognosis; single nucleotide polymorphism; squamous cell carcinoma; survival rate; tumor cell culture; tumor recurrence; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagectomy; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Genotype; Humans; Interleukin-6; Male; MicroRNAs; Middle Aged; Neoplasm Recurrence, Local; Polymorphism, Single Nucleotide; Postoperative Complications; Prognosis; Survival Rate; Tumor Cells, Cultured
Publisher
Springer New York LLC
Type
journal article