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Prognostic value of interleukin 2 and interleukin 15 in peritumoral hepatic tissues for patients with hepatitis B-related hepatocellular carcinoma after curative resection
  1. Haijun Zhou1,2,
  2. Hua Huang1,2,
  3. Jiong Shi1,2,
  4. Yue Zhao1,2,
  5. Qiongzhu Dong1,2,
  6. Huliang Jia1,2,
  7. Yinkun Liu1,2,
  8. Qinghai Ye1,2,
  9. Huichuan Sun1,2,
  10. Xiaodong Zhu1,2,
  11. Liyun Fu1,2,
  12. Kun Guo1,2,
  13. Dongmei Gao1,2,
  14. Jian Sun1,2,
  15. Zhaowei Yan1,2,
  16. Ning Ren1,2,
  17. Zhaoyou Tang1,2,
  18. Lunxiu Qin1,2
  1. 1Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai, China
  2. 2Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, China
  1. Correspondence to Professor Lunxiu Qin, Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China; qin.lunxiu{at}


Background and aims Th1/Th2-like cytokine mRNA levels in non-cancerous hepatic tissues from patients with hepatocellular carcinoma (HCC) are associated with metastases and recurrence. This study evaluated the prognostic values of intratumoral and peritumoral Th1/Th2 cytokine protein levels in patients with HCC after curative resection.

Methods Two independent cohorts (A and B) of 453 patients with HCC were enrolled. Twelve Th1/Th2 cytokines in tumour and peritumoral hepatic tissues from cohort A (n=192) were quantified with enzyme-linked immunosorbent assays. This cohort was split into training and test sets which were used to identify and verify the prognostic cytokines. The prognostic values of identified cytokines were further validated in cohort B (n=261) using tissue microarray and immunohistochemical staining.

Results In the training set, higher interleukin (IL)-2 and IL-15 levels in peritumoral liver tissues, but not in tumour tissues, were significantly associated with a decreased incidence of recurrence of intrahepatic tumour and a prolonged overall survival. This association was verified in the testing set and further validated in patients in cohort B. Importantly, this correlation remained significant in patients with early HCC. Univariate and multivariate analyses indicated that the prognostic performance of peritumoral IL-2 (HR for recurrence=0.4, 95% CI 0.3 to 0.6, p<0.0001; HR for death=0.6, 95% CI 0.4 to 0.8, p=0.005) and IL-15 (HR for recurrence=0.7, 95% CI 0.5 to 0.95, p=0.025) was independent of other clinicopathological factors.

Conclusion Peritumoral IL-2 and IL-15 levels are useful for stratifying patients, even those with early-stage HCC, into subgroups with different prognoses after curative resection.

  • Hepatocellular carcinoma/IL-2/IL-15
  • cancer

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  • Funding This work was supported by China National Key Projects for Infectious Disease (2008ZX10002-021), the “973” State Key Basic Research Program of China (2009CB521701), the China National High-tech Research and Development Program (863 Program) (2006AA02Z473), Program of Shanghai Chief Scientist (08XD1400800) and the Fund for New Teachers of Chinese Education Ministry (070246118).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Zhongshan Hospital Research ethics committee and informed consent was obtained according to the committee's regulations and the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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