High expression of IL-9R promotes the progression of human hepatocellular carcinoma and indicates a poor clinical outcome

Li,Hong-Jun; Sun,Qi-Man; Liu,Long-Zi; Zhang,Jun; Huang,Jun; Wang,Cheng-Hong; Ding,Rui; Song,Kang; Tong,Zhong

doi:10.3892/or.2015.4060

High expression of IL-9R promotes the progression of human hepatocellular carcinoma and indicates a poor clinical outcome

Authors:
- Hong-Jun Li
- Qi-Man Sun
- Long-Zi Liu
- Jun Zhang
- Jun Huang
- Cheng-Hong Wang
- Rui Ding
- Kang Song
- Zhong Tong
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Affiliations: Department of Hepatobiliary Surgery, The First People's Hospital of Hefei, Anhui 230000, P.R. China, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
Published online on: June 15, 2015 https://doi.org/10.3892/or.2015.4060
Pages: 795-802

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Abstract

Interleukin-9 receptor (IL-9R) overexpression has a pivotal role in human hematological malignancies. However, the expression of IL-9R and its biological role in human solid tumors remains elusive. In the present study, western blot analysis and RT-qPCR were used to determine the expression of IL-9R in hepatocellular carcinoma (HCC) cell lines and tumor tissues. Proliferation, cell cycle, apoptosis and Transwell assays were used to examine the biological role of IL-9R in HCC cells. The results showed that IL-9R and its ligand IL-9 were constitutively expressed in HCC cells and tissues. Moreover, the expression levels of IL-9R and IL-9 were significantly higher in tumor tissues compared to the peritumor liver tissues. Functional experiments suggested that IL-9R significantly promoted HCC cell proliferation, invasion and inhibited apoptosis, possibly by acting through the IL-9/IL-9R axis. After silencing IL-9R, the expression of VEGF, p-p38, p-STAT3 and MMP9, markedly decreased suggesting the potential involvement of these molecules in IL-9R activity. Immunohistochemistry‑based survival analysis revealed that a differential expression of IL-9R in HCC tissue was a significant and independent prognostic factor for survival [HR, 1.66; 95% confidence interval (CI), 1.17-2.36; P=0.005] and recurrence [HR, 1.50; 95%CI, 1.04‑2.17; P=0.03]. In addition, a high IL-9R expression positively and significantly correlated with larger (P=0.012) and advanced tumor stage (P=0.018). The findings indicated that IL-9R was constitutively expressed and exerted a tumor-promoting effect in HCC, whose expression level may be a useful biomarker of tumor invasiveness and patient clinical outcome.

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