Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma

K. Miyahara, K. Nouso, Y. Morimoto, Y. Takeuchi, H. Hagihara, K. Kuwaki, Hideki Ohnishi, Fusao Ikeda, Y. Miyake, S. Nakamura, Hidenori Shiraha, Akinobu Takaki, M. Honda, S. Kaneko, T. Sato, S. Sato, S. Obi, S. Iwadou, Y. Kobayashi, K. TakaguchiK. Kariyama, Y. Takuma, H. Takabatake, K. Yamamoto, Kazuhide Yamamoto, Yuki Morimoro, Yoshitaka Takuma, Hiroyuki Takabatake, Shin Ichi Fujioka, Toshiya Osawa, Kazuya Kariyama, Junichi Toshimori, Haruhiko Kobashi, Hirokazu Miyatake, Shuji Uematsu, Ryoichi Okamoto, Yasuyuki Araki, Masafumi Tatsukawa, Kazuhisa Yabushita, Toshinari Shimoe, Kohsaku Sakaguchi, Tatsuro Sakata, Toshihiko Kaneyoshi, Manabi Miyashita, Yasuhiro Makino, Akio Moriya, Masaharu Ando, Nobuyuki Baba, Tomonori Seno, Takuya Nagano, Eiji Matsumoto, Hiroki Takayama

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background:We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort.Methods:In the current retrospective cohort study, we measured serum levels of the eightcytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS).Results:Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21-2.81), and OS (HR, 1.95; 95% CI, 1.21-3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30-3.06) and OS (HR, 1.94; 95% CI, 1.19-3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis.Conclusion:High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.

Original languageEnglish
Pages (from-to)2072-2078
Number of pages7
JournalBritish Journal of Cancer
Volume109
Issue number8
DOIs
Publication statusPublished - Oct 15 2013

Fingerprint

Angiopoietin-2
Hepatocellular Carcinoma
Disease-Free Survival
Cytokines
Survival
Confidence Intervals
Serum
Follistatin
CD31 Antigens
Hepatocyte Growth Factor
Granulocyte Colony-Stimulating Factor
Leptin
Vascular Endothelial Growth Factor A
Blood Vessels
Cohort Studies
Retrospective Studies
Neoplasm Metastasis
sorafenib

Keywords

  • angiogenesis
  • angiopoietin-2
  • cytokine
  • hepatocellular carcinoma
  • sorafenib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Miyahara, K., Nouso, K., Morimoto, Y., Takeuchi, Y., Hagihara, H., Kuwaki, K., ... Takayama, H. (2013). Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma. British Journal of Cancer, 109(8), 2072-2078. https://doi.org/10.1038/bjc.2013.554

Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma. / Miyahara, K.; Nouso, K.; Morimoto, Y.; Takeuchi, Y.; Hagihara, H.; Kuwaki, K.; Ohnishi, Hideki; Ikeda, Fusao; Miyake, Y.; Nakamura, S.; Shiraha, Hidenori; Takaki, Akinobu; Honda, M.; Kaneko, S.; Sato, T.; Sato, S.; Obi, S.; Iwadou, S.; Kobayashi, Y.; Takaguchi, K.; Kariyama, K.; Takuma, Y.; Takabatake, H.; Yamamoto, K.; Yamamoto, Kazuhide; Morimoro, Yuki; Takuma, Yoshitaka; Takabatake, Hiroyuki; Fujioka, Shin Ichi; Osawa, Toshiya; Kariyama, Kazuya; Toshimori, Junichi; Kobashi, Haruhiko; Miyatake, Hirokazu; Uematsu, Shuji; Okamoto, Ryoichi; Araki, Yasuyuki; Tatsukawa, Masafumi; Yabushita, Kazuhisa; Shimoe, Toshinari; Sakaguchi, Kohsaku; Sakata, Tatsuro; Kaneyoshi, Toshihiko; Miyashita, Manabi; Makino, Yasuhiro; Moriya, Akio; Ando, Masaharu; Baba, Nobuyuki; Seno, Tomonori; Nagano, Takuya; Matsumoto, Eiji; Takayama, Hiroki.

In: British Journal of Cancer, Vol. 109, No. 8, 15.10.2013, p. 2072-2078.

Research output: Contribution to journalArticle

Miyahara, K, Nouso, K, Morimoto, Y, Takeuchi, Y, Hagihara, H, Kuwaki, K, Ohnishi, H, Ikeda, F, Miyake, Y, Nakamura, S, Shiraha, H, Takaki, A, Honda, M, Kaneko, S, Sato, T, Sato, S, Obi, S, Iwadou, S, Kobayashi, Y, Takaguchi, K, Kariyama, K, Takuma, Y, Takabatake, H, Yamamoto, K, Yamamoto, K, Morimoro, Y, Takuma, Y, Takabatake, H, Fujioka, SI, Osawa, T, Kariyama, K, Toshimori, J, Kobashi, H, Miyatake, H, Uematsu, S, Okamoto, R, Araki, Y, Tatsukawa, M, Yabushita, K, Shimoe, T, Sakaguchi, K, Sakata, T, Kaneyoshi, T, Miyashita, M, Makino, Y, Moriya, A, Ando, M, Baba, N, Seno, T, Nagano, T, Matsumoto, E & Takayama, H 2013, 'Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma', British Journal of Cancer, vol. 109, no. 8, pp. 2072-2078. https://doi.org/10.1038/bjc.2013.554
Miyahara, K. ; Nouso, K. ; Morimoto, Y. ; Takeuchi, Y. ; Hagihara, H. ; Kuwaki, K. ; Ohnishi, Hideki ; Ikeda, Fusao ; Miyake, Y. ; Nakamura, S. ; Shiraha, Hidenori ; Takaki, Akinobu ; Honda, M. ; Kaneko, S. ; Sato, T. ; Sato, S. ; Obi, S. ; Iwadou, S. ; Kobayashi, Y. ; Takaguchi, K. ; Kariyama, K. ; Takuma, Y. ; Takabatake, H. ; Yamamoto, K. ; Yamamoto, Kazuhide ; Morimoro, Yuki ; Takuma, Yoshitaka ; Takabatake, Hiroyuki ; Fujioka, Shin Ichi ; Osawa, Toshiya ; Kariyama, Kazuya ; Toshimori, Junichi ; Kobashi, Haruhiko ; Miyatake, Hirokazu ; Uematsu, Shuji ; Okamoto, Ryoichi ; Araki, Yasuyuki ; Tatsukawa, Masafumi ; Yabushita, Kazuhisa ; Shimoe, Toshinari ; Sakaguchi, Kohsaku ; Sakata, Tatsuro ; Kaneyoshi, Toshihiko ; Miyashita, Manabi ; Makino, Yasuhiro ; Moriya, Akio ; Ando, Masaharu ; Baba, Nobuyuki ; Seno, Tomonori ; Nagano, Takuya ; Matsumoto, Eiji ; Takayama, Hiroki. / Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma. In: British Journal of Cancer. 2013 ; Vol. 109, No. 8. pp. 2072-2078.
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abstract = "Background:We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort.Methods:In the current retrospective cohort study, we measured serum levels of the eightcytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS).Results:Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95{\%} confidence interval (CI), 1.21-2.81), and OS (HR, 1.95; 95{\%} CI, 1.21-3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95{\%} CI, 1.30-3.06) and OS (HR, 1.94; 95{\%} CI, 1.19-3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis.Conclusion:High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.",
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author = "K. Miyahara and K. Nouso and Y. Morimoto and Y. Takeuchi and H. Hagihara and K. Kuwaki and Hideki Ohnishi and Fusao Ikeda and Y. Miyake and S. Nakamura and Hidenori Shiraha and Akinobu Takaki and M. Honda and S. Kaneko and T. Sato and S. Sato and S. Obi and S. Iwadou and Y. Kobayashi and K. Takaguchi and K. Kariyama and Y. Takuma and H. Takabatake and K. Yamamoto and Kazuhide Yamamoto and Yuki Morimoro and Yoshitaka Takuma and Hiroyuki Takabatake and Fujioka, {Shin Ichi} and Toshiya Osawa and Kazuya Kariyama and Junichi Toshimori and Haruhiko Kobashi and Hirokazu Miyatake and Shuji Uematsu and Ryoichi Okamoto and Yasuyuki Araki and Masafumi Tatsukawa and Kazuhisa Yabushita and Toshinari Shimoe and Kohsaku Sakaguchi and Tatsuro Sakata and Toshihiko Kaneyoshi and Manabi Miyashita and Yasuhiro Makino and Akio Moriya and Masaharu Ando and Nobuyuki Baba and Tomonori Seno and Takuya Nagano and Eiji Matsumoto and Hiroki Takayama",
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TY - JOUR

T1 - Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma

AU - Miyahara, K.

AU - Nouso, K.

AU - Morimoto, Y.

AU - Takeuchi, Y.

AU - Hagihara, H.

AU - Kuwaki, K.

AU - Ohnishi, Hideki

AU - Ikeda, Fusao

AU - Miyake, Y.

AU - Nakamura, S.

AU - Shiraha, Hidenori

AU - Takaki, Akinobu

AU - Honda, M.

AU - Kaneko, S.

AU - Sato, T.

AU - Sato, S.

AU - Obi, S.

AU - Iwadou, S.

AU - Kobayashi, Y.

AU - Takaguchi, K.

AU - Kariyama, K.

AU - Takuma, Y.

AU - Takabatake, H.

AU - Yamamoto, K.

AU - Yamamoto, Kazuhide

AU - Morimoro, Yuki

AU - Takuma, Yoshitaka

AU - Takabatake, Hiroyuki

AU - Fujioka, Shin Ichi

AU - Osawa, Toshiya

AU - Kariyama, Kazuya

AU - Toshimori, Junichi

AU - Kobashi, Haruhiko

AU - Miyatake, Hirokazu

AU - Uematsu, Shuji

AU - Okamoto, Ryoichi

AU - Araki, Yasuyuki

AU - Tatsukawa, Masafumi

AU - Yabushita, Kazuhisa

AU - Shimoe, Toshinari

AU - Sakaguchi, Kohsaku

AU - Sakata, Tatsuro

AU - Kaneyoshi, Toshihiko

AU - Miyashita, Manabi

AU - Makino, Yasuhiro

AU - Moriya, Akio

AU - Ando, Masaharu

AU - Baba, Nobuyuki

AU - Seno, Tomonori

AU - Nagano, Takuya

AU - Matsumoto, Eiji

AU - Takayama, Hiroki

PY - 2013/10/15

Y1 - 2013/10/15

N2 - Background:We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort.Methods:In the current retrospective cohort study, we measured serum levels of the eightcytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS).Results:Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21-2.81), and OS (HR, 1.95; 95% CI, 1.21-3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30-3.06) and OS (HR, 1.94; 95% CI, 1.19-3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis.Conclusion:High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.

AB - Background:We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort.Methods:In the current retrospective cohort study, we measured serum levels of the eightcytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS).Results:Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21-2.81), and OS (HR, 1.95; 95% CI, 1.21-3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30-3.06) and OS (HR, 1.94; 95% CI, 1.19-3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis.Conclusion:High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.

KW - angiogenesis

KW - angiopoietin-2

KW - cytokine

KW - hepatocellular carcinoma

KW - sorafenib

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U2 - 10.1038/bjc.2013.554

DO - 10.1038/bjc.2013.554

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C2 - 24045661

AN - SCOPUS:84885929021

VL - 109

SP - 2072

EP - 2078

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 8

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