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Authors

  • Runqiu Jiang Ph.D.,

    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, P.R. China
    2. Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, P.R. China
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    • These authors contributed equally to this work

  • Chuanyong Zhang M.D.,

    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, P.R. China
    2. Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, P.R. China
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    • These authors contributed equally to this work

  • Yongxiang Xia M.D.,

    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, P.R. China
    2. Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, P.R. China
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  • Xiaofeng Qian,

    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, P.R. China
    2. Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, P.R. China
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  • Xuehao Wang M.D.,

    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, P.R. China
    2. Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, P.R. China
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  • Beicheng Sun M.D., Ph.D.

    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, P.R. China
    2. Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, P.R. China
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  • Potential conflict of interest: Nothing to report.

  • See Editorial on Page 751

Correspondence to: Beicheng Sun. E-mail: sunbc@njmu.edu.cn

Waidmann et al. reported interleukin 22 (IL-22) as a negative prognostic indicator in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Moreover, a similar analysis performed by the same group demonstrated that elevated serum IL-22 levels are independent predictors of reduced survival in patients with HCV-related liver cirrhosis.[1] We are very interested in these outcomes because in our previous research we found that IL-22 was excessively expressed in both liver cancer and adjacent cirrhotic tissues. Based on in vivo and in vitro studies, we found that IL-22 contributed to persistent liver inflammation and final hepatocarcinogenesis due to signal transducer and activator of transcription 3 (STAT3) activation. Meanwhile, we also demonstrated the significant difference in serum IL-22 concentration between HCC patients and healthy controls.[2] Due to the limitation of follow-up information, the relationship between serum IL-22 level and prognosis of HCC patients was not involved in that study.

In order to investigate whether serum IL-22 could be an indicator in prognosis of HBV-related HCC, an additional 73 hepatitis B surface antigen (HbsAg)-positive HCC patients (68.4% males) and 40 healthy controls (HbsAg-negative) were selected. Plus the previous samples, in total 92 HbsAg-positive HCC patients and 70 healthy controls were involved. The reference range was obtained by accessing 95% confidence interval (CI) in the healthy controls, which indicated that 189 pg/mL was a threshold discriminating normal from elevated levels of serum IL-22. Accordingly, 92 HCC patients were divided into two groups: ≤189 pg/mL (32 cases) and >189 pg/mL (60 cases); the overall survival (OS) rate was investigated based on follow-up data. We found that IL-22 levels (>189 pg/mL) were significantly associated with shorter OS (P = 0.010, hazard ratio [HR] 2.246, 95% CI: 1.212-4.160) (Fig. 1). Our result is similar to what Waidmann et al. reported; both of us demonstrated that high serum IL-22 concentrations were associated with poor prognosis of HCC patients with either HBV or HCV background. However, the serum IL-22 levels in healthy controls in our and several other studies are relatively higher, mainly based on an Asian population.[3-6] We speculated that this divergence was due to differences in ethnicity or determination method. Taken together, IL-22 is both a valuable diagnostic index and therapeutic target in the prevention and treatment of human HCC.

Figure 1.

Survival curves of patients with low and high IL-22 levels. Survival curves were estimated using the Kaplan-Meier method and significant differences between these two survival curves were determined using the log-rank test, P < 0.05 was considered statistically significant.

  • Runqiu Jiang, Ph.D.1,2*

  • Chuanyong Zhang, M.D.1,2*

  • Yongxiang Xia, M.D.1,2

  • Xiaofeng Qian1,2

  • Xuehao Wang, M.D.1,2

  • Beicheng Sun, M.D., Ph.D.1,2

  • 1Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine

  • Nanjing Medical University

  • Nanjing, P.R. China

  • 2Key Laboratory of Living Donor Liver Transplantation

  • Ministry of Health

  • Nanjing, P.R. China

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