TY - JOUR
T1 - Prognostic Impact of Peritumoral IL-17-Positive Cells and IL-17 Axis in Patients with Intrahepatic Cholangiocarcinoma
AU - Asukai, Kei
AU - Kawamoto, Koichi
AU - Eguchi, Hidetoshi
AU - Konno, Masamitsu
AU - Nishida, Naohiro
AU - Koseki, Jun
AU - Noguchi, Kozo
AU - Hasegawa, Shinichiro
AU - Ogawa, Hisataka
AU - Yamada, Daisaku
AU - Tomimaru, Yoshito
AU - Tomokuni, Akira
AU - Asaoka, Tadafumi
AU - Noda, Takehiro
AU - Wada, Hiroshi
AU - Gotoh, Kunihito
AU - Marubashi, Shigeru
AU - Nagano, Hiroaki
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Ishii, Hideshi
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology; a Grant-in-Aid, P-DIRECT; a Grant-in-Aid from the Ministry of Health, Labor and Welfare; a grant from the National Institute of Biomedical Innovation; and a grant from the Osaka University Drug Discovery Funds. Institutional endowments were received partially from Taiho Pharmaceutical Co., Ltd., Evidence Based Medical (EBM) Research Center, Chugai Co., Ltd., Yakult Honsha Co., Ltd., and Merck Co., Ltd. Those funders had no role in main experimental equipments, supplies expenses, study design, data collection and analysis, decision to publish, or preparation of the manuscript, in this work.
Publisher Copyright:
© 2015, Society of Surgical Oncology.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Background: Development of cancer has been linked to inflammatory cytokines such as interleukin (IL)-6 and IL-17. In this study, we assessed the expression of these cytokines in intrahepatic cholangiocarcinoma (ICC) and determined their correlation to the survival probability. Methods: A total of 72 consecutive patients who underwent curative resection of ICC at Osaka University Hospital from March 1998 to November 2014 were enrolled. Immunohistochemical analysis was performed for IL-17 and its receptor A (IL-17RA), as well as IL-6. Enzyme-linked immunosorbent assay (ELISA) was performed for preoperative plasma levels of IL-6 and IL-17 in 32 patients with ICC. Results: Immunohistochemical analysis showed that the IL-6high (n = 34) and IL-17RAhigh (n = 29) groups had significantly worse disease-free survival (DFS) than IL-6low (n = 38) and IL-17RAlow (n = 43) groups, respectively. Although IL-17+ cells were abundant in the intratumoral area, patients with high peritumoral, but not intratumoral, IL-17+ cells (n = 28) corresponded with a significantly lower overall survival (OS) and DFS (OS, p = 0.023; DFS, p = 0.026) than those with low group. Moreover, multivariate Cox proportional hazards analysis revealed that IL-6, peritumoral IL-17+, and IL-17RA are independent prognostic factors for DFS (p = 0.023, p = 0.0088, p = 0.039, respectively). In addition, high preoperative plasma levels of IL-6 in patients with ICC corresponded with significantly lower DFS (p = 0.002). Conclusions: Our data suggested that IL-6, peritumoral IL-17+ cells, and IL-17RA expression are postoperative useful markers for predicting recurrence in patients with ICC.
AB - Background: Development of cancer has been linked to inflammatory cytokines such as interleukin (IL)-6 and IL-17. In this study, we assessed the expression of these cytokines in intrahepatic cholangiocarcinoma (ICC) and determined their correlation to the survival probability. Methods: A total of 72 consecutive patients who underwent curative resection of ICC at Osaka University Hospital from March 1998 to November 2014 were enrolled. Immunohistochemical analysis was performed for IL-17 and its receptor A (IL-17RA), as well as IL-6. Enzyme-linked immunosorbent assay (ELISA) was performed for preoperative plasma levels of IL-6 and IL-17 in 32 patients with ICC. Results: Immunohistochemical analysis showed that the IL-6high (n = 34) and IL-17RAhigh (n = 29) groups had significantly worse disease-free survival (DFS) than IL-6low (n = 38) and IL-17RAlow (n = 43) groups, respectively. Although IL-17+ cells were abundant in the intratumoral area, patients with high peritumoral, but not intratumoral, IL-17+ cells (n = 28) corresponded with a significantly lower overall survival (OS) and DFS (OS, p = 0.023; DFS, p = 0.026) than those with low group. Moreover, multivariate Cox proportional hazards analysis revealed that IL-6, peritumoral IL-17+, and IL-17RA are independent prognostic factors for DFS (p = 0.023, p = 0.0088, p = 0.039, respectively). In addition, high preoperative plasma levels of IL-6 in patients with ICC corresponded with significantly lower DFS (p = 0.002). Conclusions: Our data suggested that IL-6, peritumoral IL-17+ cells, and IL-17RA expression are postoperative useful markers for predicting recurrence in patients with ICC.
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U2 - 10.1245/s10434-015-4782-y
DO - 10.1245/s10434-015-4782-y
M3 - Article
C2 - 26228109
AN - SCOPUS:84952874365
VL - 22
SP - 1524
EP - 1531
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
SN - 1068-9265
ER -
