Prognostic Impact of Peritumoral IL-17-Positive Cells and IL-17 Axis in Patients with Intrahepatic Cholangiocarcinoma

Kei Asukai, Koichi Kawamoto, Hidetoshi Eguchi, Masamitsu Konno, Naohiro Nishida, Jun Koseki, Kozo Noguchi, Shinichiro Hasegawa, Hisataka Ogawa, Daisaku Yamada, Yoshito Tomimaru, Akira Tomokuni, Tadafumi Asaoka, Takehiro Noda, Hiroshi Wada, Kunihito Gotoh, Shigeru Marubashi, Hiroaki Nagano, Yuichiro Doki, Masaki MoriHideshi Ishii

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1524-1531
Number of pages8
JournalAnnals of Surgical Oncology
Volume22
DOIs
Publication statusPublished - Dec 1 2015
Externally publishedYes

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Cholangiocarcinoma
Interleukin-17
Interleukins
Interleukin-6
Disease-Free Survival
Survival
Interleukin-17 Receptors
Cytokines
Enzyme-Linked Immunosorbent Assay
Recurrence
Neoplasms

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Prognostic Impact of Peritumoral IL-17-Positive Cells and IL-17 Axis in Patients with Intrahepatic Cholangiocarcinoma. / Asukai, Kei; Kawamoto, Koichi; Eguchi, Hidetoshi; Konno, Masamitsu; Nishida, Naohiro; Koseki, Jun; Noguchi, Kozo; Hasegawa, Shinichiro; Ogawa, Hisataka; Yamada, Daisaku; Tomimaru, Yoshito; Tomokuni, Akira; Asaoka, Tadafumi; Noda, Takehiro; Wada, Hiroshi; Gotoh, Kunihito; Marubashi, Shigeru; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi.

In: Annals of Surgical Oncology, Vol. 22, 01.12.2015, p. 1524-1531.

Research output: Contribution to journalArticle

Asukai, K, Kawamoto, K, Eguchi, H, Konno, M, Nishida, N, Koseki, J, Noguchi, K, Hasegawa, S, Ogawa, H, Yamada, D, Tomimaru, Y, Tomokuni, A, Asaoka, T, Noda, T, Wada, H, Gotoh, K, Marubashi, S, Nagano, H, Doki, Y, Mori, M & Ishii, H 2015, 'Prognostic Impact of Peritumoral IL-17-Positive Cells and IL-17 Axis in Patients with Intrahepatic Cholangiocarcinoma', Annals of Surgical Oncology, vol. 22, pp. 1524-1531. https://doi.org/10.1245/s10434-015-4782-y
Asukai, Kei ; Kawamoto, Koichi ; Eguchi, Hidetoshi ; Konno, Masamitsu ; Nishida, Naohiro ; Koseki, Jun ; Noguchi, Kozo ; Hasegawa, Shinichiro ; Ogawa, Hisataka ; Yamada, Daisaku ; Tomimaru, Yoshito ; Tomokuni, Akira ; Asaoka, Tadafumi ; Noda, Takehiro ; Wada, Hiroshi ; Gotoh, Kunihito ; Marubashi, Shigeru ; Nagano, Hiroaki ; Doki, Yuichiro ; Mori, Masaki ; Ishii, Hideshi. / Prognostic Impact of Peritumoral IL-17-Positive Cells and IL-17 Axis in Patients with Intrahepatic Cholangiocarcinoma. In: Annals of Surgical Oncology. 2015 ; Vol. 22. pp. 1524-1531.
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title = "Prognostic Impact of Peritumoral IL-17-Positive Cells and IL-17 Axis in Patients with Intrahepatic Cholangiocarcinoma",
abstract = "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.",
author = "Kei Asukai and Koichi Kawamoto and Hidetoshi Eguchi and Masamitsu Konno and Naohiro Nishida and Jun Koseki and Kozo Noguchi and Shinichiro Hasegawa and Hisataka Ogawa and Daisaku Yamada and Yoshito Tomimaru and Akira Tomokuni and Tadafumi Asaoka and Takehiro Noda and Hiroshi Wada and Kunihito Gotoh and Shigeru Marubashi and Hiroaki Nagano and Yuichiro Doki and Masaki Mori and Hideshi Ishii",
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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

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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