Cancer Chemotherapy and Pharmacology

, Volume 82, Issue 5, pp 857–864 | Cite as

Changes in plasma interleukin-8 and tumor necrosis factor-α levels during the early treatment period as a predictor of the response to sorafenib in patients with unresectable hepatocellular carcinoma

  • Ayako Iida-Ueno
  • Masaru Enomoto
  • Sawako Uchida-Kobayashi
  • Atsushi Hagihara
  • Yuga Teranishi
  • Hideki Fujii
  • Hiroyasu Morikawa
  • Yoshiki Murakami
  • Akihiro Tamori
  • Le Thi Thanh Thuy
  • Norifumi KawadaEmail author
Original Article



This study aimed to identify a biomarker for predicting the response to sorafenib in patients with hepatocellular carcinoma (HCC).


Of 100 patients with unresectable HCC who received sorafenib treatment in our institute (Cohort A), 48 had stored plasma samples collected within 28 days before the start of treatment (Cohort B). Concentrations of 18 plasma cytokines were measured in plasma samples using a sandwich immunoassay with multiplexed fluorescent bead-based technology. Among 27 patients with follow-up plasma samples taken at 5–10 days of treatment (Cohort C), changes in the 18 cytokines were also evaluated.


In Cohort A, progressive disease (PD) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) was associated with poor overall survival by multivariate analysis (p = 0.024). In Cohort B, no significant differences in baseline concentrations of α-fetoprotein, des-γ-carboxy prothrombin, or the 18 cytokines were found between patients with PD and those with stable disease (SD) or partial response (PR). In Cohort C, the increase in interleukin-8 and tumor necrosis factor-α (TNF-α) was significant in the PD group (p = 0.0063 and p < 0.001, respectively) but not in the SD + PR group (p = 0.67 and p = 0.15, respectively). In addition, the fold changes in interleukin-8 and in TNF-α were correlated (p < 0.001, r = 0.67).


Changes in plasma interleukin-8 and TNF-α levels during the first few days could predict the response to sorafenib therapy in HCC patients.


Biomarker HCC IL-8 Prediction Sorafenib TNF-α 



The authors are grateful to Ms. Yoko Yasuhara, Ms. Sanae Deguchi, and Ms. Ayano Fujikawa for her technical assistance and to Dr. Misako Sato-Matsubara for her valuable comments on this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

280_2018_3681_MOESM1_ESM.docx (84 kb)
Supplementary material 1 (DOCX 83 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Ayako Iida-Ueno
    • 1
  • Masaru Enomoto
    • 1
  • Sawako Uchida-Kobayashi
    • 1
  • Atsushi Hagihara
    • 1
  • Yuga Teranishi
    • 2
  • Hideki Fujii
    • 1
  • Hiroyasu Morikawa
    • 1
  • Yoshiki Murakami
    • 1
  • Akihiro Tamori
    • 1
  • Le Thi Thanh Thuy
    • 1
  • Norifumi Kawada
    • 1
    Email author
  1. 1.Department of Hepatology, Graduate School of MedicineOsaka City UniversityOsakaJapan
  2. 2.Department of HepatologyOsaka City General HospitalOsakaJapan

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