論文

査読有り
2017年12月

Serum cytokine profiles predict survival benefits in patients with advanced hepatocellular carcinoma treated with sorafenib: a retrospective cohort study

BMC CANCER
  • Tomoyuki Hayashi
  • ,
  • Taro Yamashita
  • ,
  • Takeshi Terashima
  • ,
  • Tsuyoshi Suda
  • ,
  • Hikari Okada
  • ,
  • Yoshiro Asahina
  • ,
  • Takehiro Hayashi
  • ,
  • Yasumasa Hara
  • ,
  • Kouki Nio
  • ,
  • Hajime Sunagozaka
  • ,
  • Hajime Takatori
  • ,
  • Kuniaki Arai
  • ,
  • Yoshio Sakai
  • ,
  • Tatsuya Yamashita
  • ,
  • Eishiro Mizukoshi
  • ,
  • Masao Honda
  • ,
  • Shuichi Kaneko

17
1
開始ページ
870
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1186/s12885-017-3889-x
出版者・発行元
BIOMED CENTRAL LTD

Background: Sorafenib is a multiple receptor tyrosine kinase inhibitor known to prolong overall survival in patients with advanced hepatocellular carcinoma (HCC). Predicting this drug's survival benefits is challenging because clinical responses are rarely measurable during treatment. In this study, we hypothesized that serum cytokines levels could predict the survival of advanced HCC patients, as sorafenib targets signaling pathways activated in the tumor stromal microenvironment and potentially affects serum cytokine profiles.
Methods: Of 143 patients with advanced-stage HCC, 104 who were recruited between 2003 and 2007 received hepatic arterial infusion chemotherapy (HAIC) that mainly targets tumor epithelial cells at S-phase (cohort 1); additionally, 39 recruited between 2010 and 2012 received sorafenib, which primarily targets the stromal vascular endothelial cells. Serum samples were collected and aliquoted prior to the treatment. Serum EGF, bFGF, HGF, IFN-gamma, IL-10, IL-12, IL-2, IL-4, IL-5, IL-6, IL-8, IP-10, MIG, PDGF-BB, SCF, SDF1, TGF-beta, TGF-alpha, TNF-alpha, and VEGF-A were measured via enzyme-linked immunosorbent assays. The Modified Response Evaluation Criteria in Solid Tumors were used to assess tumor responses.
Results: The median survival time of HCC patients in cohorts 1 (HAIC-treated) and 2 (sorafenib-treated) were 12.0 and 12. 4 months, respectively. Kaplan-Meier analysis revealed no significant survival differences between the 2 groups. Patients who survived more than 2 years after sorafenib treatment exhibited higher serum levels of IL-10, IL-12, TNF-a, IL-8, SDF-1, EGF, PDGF-BB, SCF, and TGF-alpha. Furthermore, cohort 2 patients with higher serum IL-5 (>12 pg/mL), IL-8 (>10 pg/mL), PDGF-BB (>300 pg/mL), and VEGF-A (>50 pg/mL) levels achieved longer survival; cohort 1 patients did not. Hierarchical cluster analysis of 6 cytokines robustly enriched for comparison analysis between cohorts 1 and 2 (IL-5, IL-8, TGF-alpha, PDGF-BB, CXCL9, and VEGF-A) revealed that elevation of these cytokines correlated with better survival when treated with sorafenib but not with HAIC.
Conclusions: Patients who exhibited survival benefits owing to sorafenib treatment tended to present higher serum cytokines levels, potentially reflecting the activation of stromal signaling in the tumor microenvironment. Our study thus introduces novel biomarkers that may identify advanced HCC patients who may experience survival benefits with sorafenib treatment.

Web of Science ® 被引用回数 : 13

リンク情報
DOI
https://doi.org/10.1186/s12885-017-3889-x
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29258450
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000418718900005&DestApp=WOS_CPL

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