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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 8/2018

01-08-2018 | Thoracic Oncology

Circulating Interleukin-6 is Associated with Prognosis and Genetic Polymorphisms of MIR608 in Patients with Esophageal Squamous Cell Carcinoma

Authors: Pei-Wen Yang, PhD, Pei-Ming Huang, MD, PhD, Luo-Sheng Yong, MD, Ya-Han Chang, MS, Chia-Wei Wu, MS, Kuo-Tai Hua, PhD, Min-Shu Hsieh, MD, PhD, Jang-Ming Lee, MD, PhD

Published in: Annals of Surgical Oncology | Issue 8/2018

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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.
Appendix
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Metadata
Title
Circulating Interleukin-6 is Associated with Prognosis and Genetic Polymorphisms of MIR608 in Patients with Esophageal Squamous Cell Carcinoma
Authors
Pei-Wen Yang, PhD
Pei-Ming Huang, MD, PhD
Luo-Sheng Yong, MD
Ya-Han Chang, MS
Chia-Wei Wu, MS
Kuo-Tai Hua, PhD
Min-Shu Hsieh, MD, PhD
Jang-Ming Lee, MD, PhD
Publication date
01-08-2018
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 8/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6532-4

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