title: High expression of IL-9R promotes the progression of human hepatocellular carcinoma and indicates a poor clinical outcome.
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.
authors.affiliation: Department of Hepatobiliary Surgery, The First People's Hospital of Hefei, Anhui 230000, P.R. China.
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Li
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Qi-Man
authors.initials: QM
authors.lastname: Sun
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Long-Zi
authors.initials: LZ
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, The First People's Hospital of Hefei, Anhui 230000, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The First People's Hospital of Hefei, Anhui 230000, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Hepatobiliary Surgery, The First People's Hospital of Hefei, Anhui 230000, P.R. China.
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, The First People's Hospital of Hefei, Anhui 230000, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ding
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Hepatobiliary Surgery, The First People's Hospital of Hefei, Anhui 230000, P.R. China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Tong
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D053651:Receptors, Interleukin-9 / Q000096:biosynthesis / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D053651:Receptors, Interleukin-9