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, Kenji
AU - Onishi, H.
AU - Ikeda, Fusao
AU - Miyake, Y.
AU - Nakamura, Shinichiro
AU - Shiraha, H.
AU - Takaki, A.
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
N1 - Funding Information:
Kazuhiro Nouso, Hideki Onishi and Fusao Ikeda belong to a donation-funded department (Department of Molecular Hepatology, funded by MSD). Kazuhide Yamamoto received a financial support from Bayer Yakuhin Ltd. This work was supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKENHI 23590976).
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
UR - http://www.scopus.com/inward/record.url?scp=84885929021&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885929021&partnerID=8YFLogxK
U2 - 10.1038/bjc.2013.554
DO - 10.1038/bjc.2013.554
M3 - Article
C2 - 24045661
AN - SCOPUS:84885929021
SN - 0007-0920
VL - 109
SP - 2072
EP - 2078
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 8
ER -
