Kei Asukai1, Koichi Kawamoto1,2, Hidetoshi Eguchi1, Masamitsu Konno2, Naohiro Nishida2, Jun Koseki3, Kozo Noguchi1, Shinichiro Hasegawa1, Hisataka Ogawa1, Daisaku Yamada1, Yoshito Tomimaru1, Akira Tomokuni1, Tadafumi Asaoka1, Takehiro Noda1, Hiroshi Wada1, Kunihito Gotoh1, Shigeru Marubashi1, Hiroaki Nagano1,4, Yuichiro Doki1, Masaki Mori5, Hideshi Ishii6,7. 1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. 2. Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. 3. Department of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. 4. Department of Surgery, Graduate School of Medicine, Yamaguchi University, Ube City, Yamaguchi, Japan. 5. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. mmori@gesurg.med.osaka-u.ac.jp. 6. Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. hishii@gesurg.med.osaka-u.ac.jp. 7. Department of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. hishii@gesurg.med.osaka-u.ac.jp.
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-6(high) (n = 34) and IL-17RA(high) (n = 29) groups had significantly worse disease-free survival (DFS) than IL-6(low) (n = 38) and IL-17RA(low) (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.
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-6(high) (n = 34) and IL-17RA(high) (n = 29) groups had significantly worse disease-free survival (DFS) than IL-6(low) (n = 38) and IL-17RA(low) (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.
Authors: Sandra Pavicevic; Sophie Reichelt; Deniz Uluk; Isabella Lurje; Cornelius Engelmann; Dominik P Modest; Uwe Pelzer; Felix Krenzien; Nathanael Raschzok; Christian Benzing; Igor M Sauer; Sebastian Stintzing; Frank Tacke; Wenzel Schöning; Moritz Schmelzle; Johann Pratschke; Georg Lurje Journal: Cancers (Basel) Date: 2022-02-17 Impact factor: 6.639
Authors: Julia S Johansen; Jesper B Andersen; Dan Høgdall; Colm J O'Rourke; Christian Dehlendorff; Ole F Larsen; Lars H Jensen; Astrid Z Johansen; Hien Dang; Valentina M Factor; Mie Grunnet; Morten Mau-Sørensen; Douglas V N P Oliveira; Dorte Linnemann; Mogens K Boisen; Xin W Wang Journal: Clin Cancer Res Date: 2020-09-15 Impact factor: 13.801